Статті в журналах: "Up-front chemotherapy"

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&NA;. "'Up-front' chemotherapy successful in advanced germ cell tumours." Inpharma Weekly &NA;, no. 1290 (June 2001): 10. http://dx.doi.org/10.2165/00128413-200112900-00024.

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Zhong, Lai-ping, Chen-ping Zhang, Guo-xin Ren, Wei Guo, William N. William, Jian Sun, Han-guang Zhu, et al. "Randomized Phase III Trial of Induction Chemotherapy With Docetaxel, Cisplatin, and Fluorouracil Followed by Surgery Versus Up-Front Surgery in Locally Advanced Resectable Oral Squamous Cell Carcinoma." Journal of Clinical Oncology 31, no. 6 (February 20, 2013): 744–51. http://dx.doi.org/10.1200/jco.2012.43.8820.

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Purpose To evaluate induction chemotherapy with docetaxel, cisplatin, and fluorouracil (TPF) followed by surgery and postoperative radiotherapy versus up-front surgery and postoperative radiotherapy in patients with locally advanced resectable oral squamous cell carcinoma (OSCC). Patients and Methods A prospective open-label phase III trial was conducted. Eligibility criteria included untreated stage III or IVA locally advanced resectable OSCC. Patients received two cycles of TPF induction chemotherapy (docetaxel 75 mg/m2 on day 1, cisplatin 75 mg/m2 on day 1, and fluorouracil 750 mg/m2 on days 1 to 5) followed by radical surgery and postoperative radiotherapy (54 to 66 Gy) versus up-front radical surgery and postoperative radiotherapy. The primary end point was overall survival (OS). Secondary end points included local control and safety. Results Of the 256 patients enrolled onto this trial, 222 completed the full treatment protocol. There were no unexpected toxicities, and induction chemotherapy did not increase perioperative morbidity. The clinical response rate to induction chemotherapy was 80.6%. After a median follow-up of 30 months, there was no significant difference in OS (hazard ratio [HR], 0.977; 95% CI, 0.634 to 1.507; P = .918) or disease-free survival (HR, 0.974; 95% CI, 0.654 to 1.45; P = .897) between patients treated with and without TPF induction. Patients in the induction chemotherapy arm with a clinical response or favorable pathologic response (≤ 10% viable tumor cells) had superior OS and locoregional and distant control. Conclusion Our study failed to demonstrate that TPF induction chemotherapy improves survival compared with up-front surgery in patients with resectable stage III or IVA OSCC.

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Othman, Jad, Tasman Armytage, Kelly Wong, Christopher Arthur, Keith Fay, William Stevenson, Naomi MacKinlay, et al. "Intensive chemotherapy and up-front stem cell transplant for double hit lymphoma." Bone Marrow Transplantation 55, no. 7 (January 20, 2020): 1460–63. http://dx.doi.org/10.1038/s41409-020-0789-5.

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Maffezzini, Massimo, Alchiede Simonato, Marco Zanon, Marco Raber, and Giorgio Carmignani. "Up-Front Intravesical Chemotherapy for Low Stage, Low Grade Recurrent Bladder Cancer." Journal of Urology 155, no. 1 (January 1996): 91–93. http://dx.doi.org/10.1016/s0022-5347(01)66552-2.

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Hegenbart, Ute, Michael Rieger, Matthias Witzens, Manfred Hensel, and Anthony D. Ho. "Outcome of Patients with Primary Mediastinal Large B-Cell Non-Hodgkin’s Lymphomas: A Single Institution Analysis from 1996-2004." Blood 104, no. 11 (November 16, 2004): 3302. http://dx.doi.org/10.1182/blood.v104.11.3302.3302.

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Abstract Primary mediastinal large B-cell lymphoma represents a distinct subset of large B cell lymphoma, and it has been shown to occur preferentially in young females with a bulky mediastinal mass. Between 1996 and 2004, a total of 43 patients (pts) with primary mediastinal lymphoma were diagnosed and treated at our institution, 34 of them are evaluable for response and long-term follow-up. Twenty females and 14 males have been treated, the median age at diagnosis was 33 years (range: 18–56), 10 pts had stage I, 19 pts stage II and 5 pts stage III disease, respectively. Fifteen pts presented with B symptoms, LDH was increased in 68% of pts. First-line chemotherapy included CHOP (2 pts), R-CHOP (3 pts), CHOEP (8 pts), R-CHOEP (13 pts) or Mega-CHOEP (8 pts). 16 pts received Rituximab in combination with chemotherapy as front-line therapy. Complete response after first-line therapy has been observed in 71% and PR in 21% of pts. Later on, two pts in CR and 1 pt with PR relapsed after conventional chemotherapy. Radiotherapy was administered in 22 pts (65%) presenting with initial bulky disease. 19 pts have been autografted, 15 of them as part of up-front therapy. Indications for up-front autologous HCT were treatment within the Mega-CHOEP protocol (n=8), PR after first-line chemotherapy (n=3), IPI Score of 2 (n=2) and individual decision in 2 pts. Allogeneic HCT was performed as relapse therapy in 4 patients. Of the 15 pts who had up-front autologous HCT, 13 remained in CR. Overall, thirty pts were alive at the date of last contact with a median follow-up since diagnosis of 25 months (range 3–99). Three of 4 pts who had undergone allogeneic HCT in a advanced phase of disease died of transplant-related complications. In conclusion, in this patient group addition of Rituximab and/or dose-intensified first-line chemotherapy lead to a high rate of complete remissions as compared to historic controls. Whether up-front high-dose chemotherapy with autologous HCT or the administration of radiotherapy to the initial bulk improve PFS and OS remains an open question for this special lymphoma entity. The achievement of complete remission with primary treatment strategies seems to be essential to achieve long-term cure for this disease.

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Göbel, U., D. T. Schneider, G. Calaminus, H. Jürgens, H. J. Spaar, W. Sternschulte, K. Waag, and D. Harms. "Multimodal Treatment of Malignant Sacrococcygeal Germ Cell Tumors: A Prospective Analysis of 66 Patients of the German Cooperative Protocols MAKEI 83/86 and 89." Journal of Clinical Oncology 19, no. 7 (April 1, 2001): 1943–50. http://dx.doi.org/10.1200/jco.2001.19.7.1943.

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PURPOSE: To evaluate a multimodal approach including surgery and cisplatinum chemotherapy for treatment of children with malignant sacrococcygeal germ cell tumors (GCT) and to compare adjuvant and neoadjuvant strategies in advanced tumors. PATIENTS AND METHODS: Between 1983 and 1995, 71 patients with malignant sacrococcygeal GCT were prospectively enrolled onto the German protocols for nontesticular GCT Maligne Keimzelltumoren 83/86 and 89. Five patients who received no chemotherapy (n = 2) or nonplatinum chemotherapy (n = 2) or who did not undergo tumor resection (n = 1) were excluded from this analysis. Among the 66 patients analyzed were 14 boys and 52 girls. The median age was 17.4 months (range, 7 months to 119 months). Median follow-up was 79 months (range, 4 months to 145 months). RESULTS: Fifty-two patients presented with locally advanced stage T2 tumors, and 30 patients had distant metastases at diagnosis. Patients received a median of eight cycles (range, four to nine cycles) of cisplatinum-based chemotherapy. Thirty-five patients underwent tumor resection at diagnosis and received adjuvant cisplatinum-based chemotherapy (group A). Thirty-one patients received up-front chemotherapy followed by delayed tumor resection (group B). Group B included more metastatic tumors than group A (group B, 19 of 31 patients; group A, 11 of 35 patients, P = .01). Preoperative chemotherapy facilitated complete tumor resections (group B, 20 of 31 patients; group A, five of 35 patients, P < .001) and avoided second-look surgery. Metastases at diagnosis and completeness of the first attempt of tumor resection were significant prognostic predictors; however, metastases were not predictive for patients treated with up-front chemotherapy. At 5 years follow-up, event-free survival was 0.76 ± 0.05 (50 of 66 patients), and overall survival was 0.81 ± 0.05 (54 of 66 patients). Four patients died as a result of therapy-related complications, and eight patients died of their tumors. Patients with locally advanced and metastatic tumors (T2b M1) fared better with neoadjuvant treatment [overall survival: 0.83 ± 0.09 (16 of 19 patients) versus 0.45 ± 0.15 (five of 11 patients), P = .01]. CONCLUSION: Even locally advanced and metastatic sacrococcygeal GCT can be successfully treated with up-front cisplatinum-based chemotherapy followed by delayed but complete tumor resection.

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Steed, H., A. M. Oza, J. Murphy, S. Laframboise, G. Lockwood, D. De Petrillo, J. Sturgeon, and B. Rosen. "A retrospective analysis of neoadjuvant platinum-based chemotherapy versus up-front surgery in advanced ovarian cancer." International Journal of Gynecologic Cancer 16, Suppl 1 (January 2006): 47–53. http://dx.doi.org/10.1136/ijgc-00009577-200602001-00008.

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The objective of this study is to compare progression-free survival (PFS) and overall survival (OS) of ovarian cancer patients treated with neoadjuvant chemotherapy and surgery to primary surgery and postoperative chemotherapy. Retrospective analysis from 1998 to 2003 of 116 patients with ovarian cancer was performed. Fifty women diagnosed by positive cytology received three cycles of carboplatin and paclitaxel. Thirty-six patients subsequently underwent cytoreductive surgery and completed three further cycles postoperatively. The OS and PFS were compared in 66 women treated with primary surgery and postoperative chemotherapy. A statistically significant difference was observed for OS (P= 0.03, HR = 1.85, CI = 1.06–3.23) and PFS (P= 0.04, HR = 1.61, CI = 1.03–2.53) favoring the primary surgery group. Due to the small numbers, age, grade, stage, pleural effusions, and histologic cell type were controlled for separately in the bivariate analyses. Controlling for stage made the results weaker. A matched subgroup survival analysis was performed on patients who had surgery following neoadjuvant chemotherapy. After matching for stage and grade and controlling age and pleural effusions (N= 28 matched pairs), there was no statistical difference for OS (P= 0.95, HR = 1.04, CI = 0.33–3.30) or PFS (P= 0.79, HR = 1.11, CI = 0.98–1.04). It is concluded that primary surgery should be considered in all patients. Neoadjuvant chemotherapy may be an alternative in a subset of women with the intent to also perform interval debulking.

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Coccolini, Federico. "Advanced ovarian cancer: Neoadjuvant chemotherapy plus surgery and HIPEC as up-front treatment." World Journal of Obstetrics and Gynecology 1, no. 4 (2012): 55. http://dx.doi.org/10.5317/wjog.v1.i4.55.

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Rakotonjanahary, Josué, Emilie De Carli, Matthieu Delion, Chantal Kalifa, Jacques Grill, François Doz, Pierre Leblond, Anne-Isabelle Bertozzi, and Xavier Rialland. "Mortality in Children with Optic Pathway Glioma Treated with Up-Front BB-SFOP Chemotherapy." PLOS ONE 10, no. 6 (June 22, 2015): e0127676. http://dx.doi.org/10.1371/journal.pone.0127676.

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Bittoni, Alessandro, Mario Scartozzi, Mirco Pistelli, Eva Galizia, Michela Del Prete, Riccardo Giampieri, Luca Faloppi, Maristella Bianconi, Elena Maccaroni, and Stefano Cascinu. "Intensive up-front treatment versus a sequential approach in advanced gastric cancer patients: Does first line matter?" Journal of Clinical Oncology 30, no. 4_suppl (February 1, 2012): 131. http://dx.doi.org/10.1200/jco.2012.30.4_suppl.131.

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131 Background: The definition of the standard chemotherapy regimen for advanced gastric cancer is still a matter of debate. A recent meta-analysis suggested that the addition of a third drug to a doublet regimen should be considered the state-of-the-art strategy to improve overall survival. Aim of our analysis was to retrospectively assess whether an intensive, three-drugs, front line approach could be comparable to a sequential (two-drugs front line then second line) in terms of RR (response rate), PFS (progression free survival), and OS (overall survival) in advanced gastric cancer patients. Methods: Patients with metastatic gastric cancer who have received a first-line combination chemotherapy with a two or three-drugs regimen were included in our analysis. We divided our patients into two groups, A and B, based on the first line chemotherapy administered (group A=three drugs; group B= two drugs). Results: A total of 390 patients were eligible for our analysis. 211 patients (54%) received three chemotherapeutic agents (group A) and 179 patients (46%) received a two drugs regimen as first-line combination chemotherapy (group B). The 2 groups of patients resulted comparable for all known prognostic factors of clinical relevance. RR for group A and B was 46,5% and 28%, respectively (p=0,0007), median PFS was 7,12 months in group A and 3,96 months in group B (p<0,0001). No significantly difference resulted for the median OS of patients in the two groups (13 months for group A and 11,8 months for group B; p= 0,962). Conclusions: The addition of a third drug to a doublet chemotherapy regimen appeared more active in terms of response rate and PFS. However median OS resulted comparable. On this basis, a triplet regimen may represent an optimal choice, particularly when response and PFS are relevant treatment endpoints. Nevertheless the use of a sequential approach may also represent a reasonable strategy for patients unwilling or unable to undergo a more intensive treatment without compromising OS.

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Bittoni, Alessandro, Mario Scartozzi, Mirco Pistelli, Eva Galizia, Michela Del Prete, Riccardo Giampieri, Luca Faloppi, Maristella Bianconi, Elena Maccaroni, and Stefano Cascinu. "Intensive up-front treatment versus a sequential approach in advanced gastric cancer patients: Does first-line matter?" Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): e14663-e14663. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.e14663.

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e14663 Background: The definition of the standard chemotherapy regimen for advanced gastric cancer is still a matter of debate. A recent meta-analysis suggested that the addition of a third drug to a doublet regimen should be considered the state-of-the-art strategy to improve overall survival. Aim of our analysis was to retrospectively assess whether an intensive, three-drugs, front line approach could be comparable to a sequential (two-drugs front line then second line) in terms of RR (response rate), PFS (progression free survival) and OS (overall survival) in advanced gastric cancer patients. Methods: Patients with metastatic gastric cancer who have received a first-line combination chemotherapy with a two or three-drugs regimen were included in our analysis. We divided our patients into two groups, A and B, based on the first line chemotherapy administered (group A=three drugs; group B= two drugs). Results: A total of 390 patients were eligible for our analysis. 211 patients (54%) received three chemotherapeutic agents (group A) and 179 patients (46%) received a two drugs regimen as first-line combination chemotherapy (group B). The 2 groups of patients resulted comparable for all known prognostic factors of clinical relevance. RR for group A and B was 46.5% and 28%, respectively (p=0,0007), median PFS was 7.12 months in group A and 3.96 months in group B (p<0,0001). No significantly difference resulted for the median OS of patients in the two groups (13 months for group A and 11.8 months for group B; p= 0.962). Conclusions: The addition of a third drug to a doublet chemotherapy regimen appeared more active in terms of response rate and PFS. However median OS resulted comparable. On this basis, a triplet regimen may represent an optimal choice, particularly when response and PFS are relevant treatment endpoints. Nevertheless the use of a sequential approach may also represent a reasonable strategy for patients unwilling or unable to undergo a more intensive treatment without compromising OS.

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Hügli, A., D. Moro, B. Mermillod, M. Bolla, P. Alberto, H. Bonnefoi, and R. Miralbell. "Phase II Trial of Up-Front Accelerated Thoracic Radiotherapy Combined With Chemotherapy and Optional Up-Front Prophylactic Cranial Irradiation in Limited Small-Cell Lung Cancer." Journal of Clinical Oncology 18, no. 8 (April 8, 2000): 1662–67. http://dx.doi.org/10.1200/jco.2000.18.8.1662.

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PURPOSE: To investigate the feasibility and outcome of bifractionated, up-front thoracic radiotherapy (TR) (45 Gy in 30 fractions of 1.5 Gy twice daily over 3 weeks) combined with chemotherapy (CT) (six cycles of cisplatin and etoposide) and optional low-dose, up-front prophylactic cranial irradiation (18 Gy in 10 fractions of 1.8 Gy twice daily over 5 days) in limited small-cell lung cancer. PATIENTS AND METHODS: CT (etoposide 100 mg/m2 for 3 days and cisplatin 25 mg/m2 for 3 days) was started on day 8 or 15 after the first TR treatment. In the five subsequent cycles, cisplatin was given as a single 100-mg/m2 dose on day 1 every 4 weeks. A total of 52 patients were entered (41 men and 11 women); the median age was 55 years (range, 33 to 67 years). World Health Organization performance status was 0 in 34 patients, 1 in 16 patients, and 2 in two patients. Thirty-six patients (69%) received the full planned six cycles of CT. RESULTS: All treated patients were assessable for response. Thirty-one patients (60%) achieved a complete response, and 16 (30%) had a partial response. One-, 3-, and 4-year survival rates were 74% (95% confidence interval [CI], 60% to 84%), 34% (95% CI, 21% to 49%), and 32% (95 CI, 16% to 46%), respectively. The median survival time was 18 months. Event-free survival at 1 year was 45% (95% CI, 32% to 58%) and at 3 years, 30% (95% CI, 18% to 44%). The main radiation-related acute toxicity was esophageal: 38% of the patients experienced grade 3 or 4 acute toxicity. CT was well tolerated. Although grade 3/4 neutropenia was observed in 86% of the patients, only 4% presented with associated fever. Grade 3/4 nausea and vomiting was seen in 35% of patients. CONCLUSION: This trial demonstrates that up-front accelerated TR associated with CT is feasible, has acceptable toxicity, and shows considerable long-term survival potential.

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Manyam, Bindu V., Shlomo A. Koyfman, Davendra Sohal, Ismail Mallick, Chandana A. Reddy, Feza H. Remzi, Matthew F. Kalady, Ian C. Lavery, Ravi P. Kiran, and May Abdel-Wahab. "Does up-front definitive surgical resection with delayed chemotherapy in patients with stage IV rectal cancer compromise overall survival?" Journal of Clinical Oncology 32, no. 3_suppl (January 20, 2014): 586. http://dx.doi.org/10.1200/jco.2014.32.3_suppl.586.

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586 Background: Definitive resection of the primary is frequently part of the management of patients (pts) with stage IV rectal cancer with good performance status and low volume of systemic metastases. It is unclear whether delaying systemic therapy for up front surgical management of the primary compromises overall survival (OS). Methods: Pts with metastatic rectal adenocarcinoma who received definitive surgical resection between 1998-2011 were identified in an IRB approved registry. The sequencing of CT and surgery, and the use of perioperative radiation therapy (RT), was at the discretion of treating physicians. Preoperative chemotherapy (Pre-CT) regimens included 5-fluorouracil (5-FU) +/- leukovorin (LV), capecitabine, 5-FU/LV/oxaliplatin +/- avastin, or 5-FU/LV/irinocetan. RT dose was typically 50.4 Gy. OS was measured from the date of diagnosis. Baseline variables were compared using the Chi-square and unpaired t-tests. OS was calculated using the Kaplan Meier method. Univariate (UVA) and multivariate analysis (MVA) were performed using Cox proportional hazards regression to identify variables associated with OS. Results: In this study of 115 pts, 75 (65%) were treated with pre-CT, while 40 (35%) were treated with up front surgery. Of the pts who received surgery up front, 3 (8%) received RT and of the pts who received pre-CT, 62 (83%) received RT. The cohort was predominantly male (70%) with a median age of 57, median KPS of 80, and median follow-up of 24.1 months. 94% of pts had T3/T4 tumors, 80% had N+ disease, and 33% had poorly differentiated tumors. Liver directed therapy (LDT) was performed in 61% of pts. There was no significant difference in OS (32.3 vs. 32 months; p = 0.24) between pts treated with pre-CT and those who received surgery up front, respectively. UVA demonstrated that pre-CT was not associated with OS (HR 1.26; p = 0.544). MVA demonstrated that pts with poorly differentiated tumors (HR 2.04; p = 0.007) and those that did not undergo LDT (HR 2.45; p = 0.001) had inferior survival. Conclusions: Delaying systemic chemotherapy in order to achieve local control with surgical resection up front does not appear to impact OS in pts with stage IV rectal cancer.

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Mitomi, Takahiro, Takashi Kawahara, Yasuhide Miyoshi, and Hiroji Uemura. "Effectiveness and Feasibility of Up-Front Docetaxel Chemotherapy for Japanese Metastatic Hormone-Naïve Prostate Cancer." SN Comprehensive Clinical Medicine 3, no. 8 (May 20, 2021): 1715–16. http://dx.doi.org/10.1007/s42399-021-00939-8.

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Mølby, A. W., B. E. Laursen, U. Falkmer, T. McCulloch, N. A. Jensen, and L. Ø. Poulsen. "Up front chemotherapy dosing and relative dose intensity in extensive stage small cell lung cancer." Annals of Oncology 28 (April 2017): ii17—ii18. http://dx.doi.org/10.1093/annonc/mdx088.004.

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Kamat, A., E. Chiong, J. Taylor, A. Siefker-Radtke, H. Grossman, and C. Dinney. "POD-7.03: Micropapillary Bladder Cancer: Comparison of Outcomes with Up-front Cystectomy and Neoadjuvant Chemotherapy." Urology 72, no. 5 (November 2008): S55—S56. http://dx.doi.org/10.1016/j.urology.2008.08.156.

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Wegner, Rodney, Stephen Abel, Tulika Ranjan, Richard Williamson, Alexander Yu, Linda Xu, and Stephen Karlovits. "RTHP-24. TRENDS IN THE UP FRONT USE OF STEREOTACTIC RADIOSURGERY FOR GLIOBLASTOMA." Neuro-Oncology 21, Supplement_6 (November 2019): vi214—vi215. http://dx.doi.org/10.1093/neuonc/noz175.895.

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Abstract BACKGROUND GBM is typically managed with a combined modality approach including resection followed by adjuvant chemoradiation. Despite aggressive up front treatment local failure occurs in the vast majority of patients. The concept of dose escalation through use of stereotactic radiosurgery (SRS) was tested in RTOG 9305 in the pre-temozolomide era with the hopes of improving control, ultimately showing no benefit. We used the National Cancer Database (NCDB) to examine trends in the use of up-front SRS, to see if it had truly fallen out of favor, and if it had any impact on outcome. METHODS We queried the NCDB from 2004–14 for GBM patients that had radiation and 2 months of follow up. Odds ratios were used to determine predictors of SRS. Univariable and multivariable Cox regressions were used to determine potential predictors of overall survival (OS). Propensity adjusted multivariable analysis was used to account for any indication bias. RESULTS We identified 62,681 patients meeting eligibility criteria, of which 1,046 had SRS. SRS decreased over time from 3% to less than 1%. Predictors of SRS were increased age, government insurance, lower comorbid score, treatment at an academic facility, metropolitan location, increased distance to facility, smaller tumor, lack of surgery, no chemotherapy, and more remote year of treatment. Median overall survival was 13.1 months in the non-SRS group and 12.9 months in the SRS group, p=0.28. On multivariable analysis increased age, lack of chemotherapy, higher comorbidity score, extent of surgery, non-academic facility, decreased education, government insurance, urban location, Caucasian race, male gender, larger tumor, and more remote year of treatment predicted for worse overall survival. CONCLUSIONS Use of up-front SRS in the management of GBM has decreased over time, in concordance with past randomized trials examining its use. Our analysis did not show any benefit in survival with its use.

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Saiura, Akio, Yosuke Inoue, Yoshihiro Mise, Yu Takahashi, Takafumi Ichida, and Takeaki Ishizawa. "Impact of preoperative chemotherapy on overall survival for borderline resectable colorectal liver metastases." Journal of Clinical Oncology 34, no. 4_suppl (February 1, 2016): 365. http://dx.doi.org/10.1200/jco.2016.34.4_suppl.365.

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365 Background: Treatment for borderline colorectal liver metastases (CLM) is often started with chemotherapy. However, the impact on overall survival (OS) is still unknown. Aims: The aim of this study is to analyze the impact of preoperative chemotherapy on the outcome for up-front resectable borderline CLMs (BLR-CLM). Methods: A retrospective review was performed of 169 patients who underwent liver resection of BLR-CLM among 510 patients underwent liver resection for CLM between 2005 and 2013. BLR-CRLM was defined as CRLM of four or more nodules or 5cm or larger nodule. Time to surgical failure (TSF) was defined as the time until unresectable relapse or death. OS, recurrence free survival (RFS) and TSF were compared between BLR-CLM treated with neoadjuvant chemotherapy (NAC) and up-front surgery (US). Results: After median follow-up period of 38 months, 5-year survival rate after liver resection of resectable cases (n = 263), BLR-CLM (n = 169), and initially unresectable CLM (n = 78) are 67.7%, 47.5% and 32.6%, respectively. For patients with BLR-CLM, 22 patients with early recurrence during or early after postoperative chemotherapy for the primary were excluded. In the remaining 147 patients, 75 patients were treated with NAC and 72 with US. Cumulative 5-year overall survival rates, progression free survival rates, and time-to surgical failure in NAC and US group are as follows: OS (60.1% vs 47.7%, p = 0.084), PFS (23.1% vs 15.5%, p < 0.0001), TSF (38.0% vs 34.4%, p = 0.020). Conclusions: Preoperative chemotherapy for BLR-CLM could improve PFS and TSF. The impact on OS was still marginal. Prospective controlled study will be necessary.

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Serretta, V., G. Corselli, F. Piazza, G. B. Ingargiola, G. Lo Greco, C. Pavone, and M. Pavone-Macaluso. "Neoadjuvant chemotherapy, TUR and radiotherapy in T2-T4 NO MO bladder carcinoma." Urologia Journal 64, no. 4 (August 1997): 416–18. http://dx.doi.org/10.1177/039156039706400409.

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– Forty patients affected by locally advanced carcinoma of the bladder were submitted to up-front chemotherapy followed by TUR and radiotherapy. A complete response was obtained in 27 patients (67.5%). A residual mass was present in 13 (32.5%) patients. At a mean follow-up of 38 months (range: 18–112 months), 7 patients showed a recurrence that was superficial in 3 cases and infiltrating the muscular layer in 4. Fifteen patients (37.5%), 12 of whom disease-free, are alive with a mean survival of 65 months. Five more patients died of non-related disease.

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Kapoor, Akhil, Vikas S. Ostwal, Nikhil Pande, Anant Ramaswamy, Rushab Kothari, Reena Engineer, Ashwin Desouja, Suprita Arya, Mukta Ramadwar, and Avanish Saklani. "Up-front short-course radiotherapy and systemic chemotherapy for locally advanced rectal cancers with distant metastasis: Does it provide meaningful benefit?" Journal of Clinical Oncology 36, no. 4_suppl (February 1, 2018): 778. http://dx.doi.org/10.1200/jco.2018.36.4_suppl.778.

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778 Background: The optimal sequencing of treatment for locally advanced rectal cancer with distant metastasis (mLARC) is not well established. Methods: We retrospectively reviewed the records of mLARC patients receiving SCRT (25Gy/5#) and chemotherapy between July 2013 and December 2016. Patients were evaluated for surgery after SCRT and chemotherapy with the decision for further treatment being taken in a multidisciplinary team. Those patients who underwent surgery also received adjuvant chemotherapy as per the standard practice. Results: One hundred five consecutive mLARC patients were included in this study. Median age was 48 years (range 16-78) and 60 patients (57%) were male. Thirty-six patients (34%) had a single site of metastases. Sixty-one patients (58%) had obstruction at baseline and required stoma placement and another 19 patients (18%) had near obstructive lesions; these patients did not require stoma post SCRT and chemotherapy. With first line chemotherapy, objective response rate was 39% while 29% patients had stable disease. Twenty-four patients (23%) underwent definitive surgery. Median PFS and OS for entire cohort was 10.5 months (95% CI: 9.1-11.8) and 15.7 months (95% CI: 10.2-21.2), respectively. Median PFS was 23 months (95% CI: 18.7-27.7) for patients who could undergo surgery while it was 7.7 months (95% CI: 5.9-9.5, HR 5.0) (log rank <0.001) for patients in whom surgery was not possible. Median OS was not reached for patients who underwent surgery while it was 10.9 months (95% CI: 9.6-12.3, HR 9.8) (log rank p<0.001) for patients in whom surgery was not possible. OS at 3 years was 60% for patients who underwent surgery while it was only 7% in whom surgery was not possible. Conclusions: Upfront SCRT followed by systemic chemotherapy with delayed surgery in locally advanced rectal cancer with distant metastasis is an effective, feasible and attractive option. [Table: see text]

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Schmid, Peter, Walter Schippinger, Thorsten Nitsch, Gerdt Huebner, Volker Heilmann, Wolfgang Schultze, Hubert Hausmaninger, Manfred Wischnewsky, and Kurt Possinger. "Up-Front Tandem High-Dose Chemotherapy Compared With Standard Chemotherapy With Doxorubicin and Paclitaxel in Metastatic Breast Cancer: Results of a Randomized Trial." Journal of Clinical Oncology 23, no. 3 (January 20, 2005): 432–40. http://dx.doi.org/10.1200/jco.2005.06.072.

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Purpose The role of high-dose chemotherapy (HDCT) in metastatic breast cancer remains controversial. Trials with late intensification HDCT have failed to show an advantage in overall survival. This study was initiated to compare up-front tandem HDCT and standard combination therapy in patients with metastatic breast cancer. Patients and Methods Patients without prior chemotherapy for metastatic disease were randomly assigned to standard combination therapy with doxorubicin and paclitaxel (AT) or double HDCT with cyclophosphamide, mitoxantrone, and etoposide followed by peripheral-blood stem-cell transplantation. HDCT was repeated after 6 weeks. Patients were stratified by menopausal and hormone-receptor status. The primary objective was to compare complete response (CR) rates. Results A total of 93 patients were enrolled onto the trial. Intent-to-treat CR rates for patients randomized to HDCT and AT were 12.5% and 11.1%, respectively (P = .84). Objective response rates were 66.7% for patients in the high-dose group and 64.4% for patients in the AT arm (P = .82). In an intent-to-treat analysis, there were no significant differences between the two treatments in median time to progression (HDCT, 11.1 months; AT, 10.6 months; P = .67), duration of response (HDCT, 13.9 months; AT, 14.3 months; P = .98), and overall survival (HDCT, 26.9 months; AT, 23.4 months; P = .60). HDCT was associated with significantly more myelosuppression, infection, diarrhea, stomatitis, and nausea and vomiting, whereas patients treated with AT developed more neurotoxicity. Conclusion This trial failed to show a benefit for up-front tandem HDCT compared with standard combination therapy. HDCT was associated with more acute adverse effects.

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Muratore, Andrea, Daria Zorzi, Hedayat Bouzari, Marco Amisano, Paolo Massucco, Elisa Sperti, and Lorenzo Capussotti. "Asymptomatic Colorectal Cancer with Un-Resectable Liver Metastases: Immediate Colorectal Resection or Up-Front Systemic Chemotherapy?" Annals of Surgical Oncology 14, no. 2 (November 14, 2006): 766–70. http://dx.doi.org/10.1245/s10434-006-9146-1.

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STEED, H., A. M. OZA, J. MURPHY, S. LAFRAMBOISE, G. LOCKWOOD, D. DE PETRILLO, J. STURGEON, and B. ROSEN. "A retrospective analysis of neoadjuvant platinum-based chemotherapy versus up-front surgery in advanced ovarian cancer." International Journal of Gynecological Cancer 16, S1 (February 2006): 47–53. http://dx.doi.org/10.1111/j.1525-1438.2006.00472.x.

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Tanaka, Yuka, Takayuki Tabayashi, Yasuyuki Takahashi, Yuta Kimura, Tatsuki Tomikawa, Tomoe Anan, Morihiko Sagawa, Reiko Watanabe, Michihide Tokuhira, and Masahiro Kizaki. "Up-front high-dose chemotherapy followed by autologous stem cell transplantation for high-risk aggressive lymphoma." Annals of Oncology 28 (October 2017): ix102. http://dx.doi.org/10.1093/annonc/mdx621.029.

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Moscetti, Luca, Fabrizio Nelli, Alessandra Felici, Massimo Rinaldi, Stefano De Santis, Giuliana D'Auria, Giovanni Mansueto, Giuseppe Tonini, Isabella Sperduti, and Francesco C. Pollera. "Up-front chemotherapy and radiation treatment in newly diagnosed nonsmall cell lung cancer with brain metastases." Cancer 109, no. 2 (2007): 274–81. http://dx.doi.org/10.1002/cncr.22399.

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Rovers, Koen P., Checca Bakkers, Felice N. van Erning, Jacobus W. A. Burger, Simon W. Nienhuijs, Geert A. A. M. Simkens, Geert-Jan M. Creemers, et al. "Adjuvant Systemic Chemotherapy vs Active Surveillance Following Up-front Resection of Isolated Synchronous Colorectal Peritoneal Metastases." JAMA Oncology 6, no. 8 (August 13, 2020): e202701. http://dx.doi.org/10.1001/jamaoncol.2020.2701.

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Hasler-Strub, Ursula. "Use of First-Line PARP Inhibitors in Ovarian Cancer." healthbook TIMES Oncology Hematology, no. 2 (December 5, 2019): 26–29. http://dx.doi.org/10.36000/hbt.oh.2019.02.006.

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Platinum-based chemotherapy regimens are the mainstay of advanced ovarian cancer treatment. However, up to 85% of the patients experience recurrence under these settings. To fill this gap, novel front-line treatment strategies have been established, leading to unprecedented clinical benefits. For example, first-line bevacizumab, an anti-angiogenic agent, plus chemotherapy followed by bevacizumab maintenance, has emerged as a new standard of care for newly diagnosed high risk ovarian cancer patients. This was based on the results of the phase III GOG 0218 and ICON-7 trials. More recently, poly(ADP)-ribose polymerase (PARP) inhibitors, including niraparib, olaparib and veliparib, have offered a new treatment option as part of the front-line treatment in ovarian cancer. Here we provide an overview of three recent studies that may lead to a paradigm shift in the first-line treatment for advanced ovarian cancer.

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Dood, Robert, Nicole D. Fleming, Robert L. Coleman, Shannon Neville Westin, and Anil Sood. "When advanced ovarian cancer is not ovarian cancer." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): e17066-e17066. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.e17066.

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e17066 Background:Tissue diagnosis of advanced ovarian cancer (OC) is not universally obtained prior to up-front surgery. This study sought to investigate non-OC cases discovered in the systemic laparoscopic (LSC) workup of presumed advanced OC. Methods: A prospective cohort of presumed advanced OC patients (based on elevated CA125 and/or imaging) presenting to our center without confirmed pathologic diagnosis. Patients with non-OC pathology confirmed in workup were characterized and compared to those with confirmed ovarian pathology using standard statistical tests. Results: 365 patients presented between 5/30/12 and 11/16/16. Non-OC was found in 27 cases (7.4%), including benign ovarian pathology (48%), and metastatic uterine (11%), breast (7%) and gastrointestinal (19%) cancers. A majority used diagnostic LSC or assessment at time of up-front surgery (see Table) for diagnosis. Non-OC cases were less likely to be confirmed by FNA or core biopsy, were more common in Asian patients, had better ECOG scores, and had a lower CA125. Only 1 non-OC patient (uterine sarcoma) received neo-adjuvant chemotherapy. Conclusions: A systematic LSC approach to advanced stage OC minimizes incorrect chemotherapy chemotherapy administration. Asian patients and those with low CA125 values are at highest risk of a false diagnosis of OC, but did not routinely have a diagnostic opportunity prior to systematic LSC. [Table: see text]

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Goldstein, L. J., and M. Shapiro. "Up-Front Tandem High-Dose Chemotherapy Compared With Standard Chemotherapy With Doxorubicin and Paclitaxel in Metastatic Breast Cancer: Results of a Randomized Trial." Breast Diseases: A Year Book Quarterly 16, no. 4 (January 2006): 377. http://dx.doi.org/10.1016/s1043-321x(05)80311-x.

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Nortier, J. W., and A. Ogilvie. "A phase II study of early up-front red blood cell transfusion followed by maintenance epoetin-alpha subcutaneously support during chemotherapy." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): e20719-e20719. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.e20719.

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e20719 Background: To determine in patients with cancer related anaemia (Hb<11,3 g/d) starting with their chemotherapy the efficacy and safety of up-front red blood cell transfusion and subsequently maintenance epoetin-alpha (Epo) administration. The study target was the range of low-normal Hb levels of 11,3 to 12,9 g/dL aiming at improving tumor oxygenation. Methods: A multicenter, open label, single-arm phase II study. All eligible patients with metastatic solid cancers received around their first or second chemotherapy cycle a transfusion of 1–3 units of erythrocytes depending on their Hb level. This was followed by Epo subcutaneously weekly at an initial dose of 40,000 IU during the chemotherapy period. Epo was only administered when the Hb level was below the lower margin of the target Hb range. All patients started with pre-emptive oral iron suppletion. Primary objectives were: correction of anemia to the Hb level target range and safety. Secondary objectives were: Quality of Life, Length of Treatment Duration and Time to Treatment Failure. Safety included: blood pressure, thrombo-embolic events, adverse events and serious adverse event. Results: 18 Patients enrolled in this study from March 30, 2006 to November 11, 2008. An intention-to-treatment analysis was performed for the primary objectives in 16 patients (8 with breast-, 4 with colorectal-, 1 with ovarian- and 1 with pancreatic cancer) and reported here. Patients were during a median of 12 weeks (range 1 to 32 weeks) on study. Median Hb increased from 10,2 g/dL to 11,2 g/dL after transfusion and stayed at that level during the first 19 weeks of Epo administration; Hb levels were between 10,0 and 11,5 g/dL. In the following period until the final 32nd studyweek, Hb levels increased slightly, ranging from 10,3 to 11,8 g/dL. Two patients remained during the study in the Hb level target range. The safety of Epo was good. Grade 3/4 adverse events and serious adverse events that occurred were found to be all chemotherapy or progressive disease related. Conclusions: Although this up-front treatment increased Hb to stable levels during chemotherapy, the target Hb levels were not reached in most patients. This was presumably related to the lesser than projected yield of the red blood cell transfusion. [Table: see text]

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Rotow, Julia K., and Pasi A. Jänne. "What’s Old Is New Again: Revisiting Up-Front Chemotherapy in EGFR-Mutated Non–Small-Cell Lung Cancer." Journal of Clinical Oncology 38, no. 2 (January 10, 2020): 107–10. http://dx.doi.org/10.1200/jco.19.02724.

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Fallah, Jaleh, and Adam J. Olszewski. "Variation in the use of up-front chemotherapy for indolent B-cell lymphomas and chronic lymphocytic leukemia." Hematological Oncology 35, no. 4 (December 16, 2016): 921–24. http://dx.doi.org/10.1002/hon.2382.

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Riechelmann, Herbert, Teresa Bernadette Steinbichler, Susanne Sprung, Matthias Santer, Annette Runge, Ute Ganswindt, Gabriele Gamerith, and Jozsef Dudas. "The Epithelial-Mesenchymal Transcription Factor Slug Predicts Survival Benefit of Up-Front Surgery in Head and Neck Cancer." Cancers 13, no. 4 (February 12, 2021): 772. http://dx.doi.org/10.3390/cancers13040772.

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EMT promotes radio- and chemotherapy resistance in HNSCC in vitro. As EMT has been correlated to the transcription factor Slug in tumor specimens from HNSCC patients, we assessed whether Slug overexpression predicts radio- and chemotherapy resistance and favors upfront surgery in HNSCC patients. Slug expression was determined by IHC scoring in tumor specimens from patients with incident HNSCC. Patients were treated with either definitive radiotherapy or chemoradiotherapy (primary RT/CRT) or upfront surgery with or without postoperative RT or CRT (upfront surgery/PORT). Treatment failure rates and overall survival (OS) were compared between RT/CRT and upfront surgery/PORT in Slug-positive and Slug-negative patients. Slug IHC was positive in 91/354 HNSCC patients. Primary RT/CRT showed inferior response rates (univariate odds ratio (OR) for treatment failure, 3.6; 95% CI, 1.7 to 7.9; p = 0.001) and inferior 5-year OS (univariate, p < 0.001) in Slug-positive patients. The independent predictive value of Slug expression status was confirmed in a multivariable Cox model (p = 0.017). Slug-positive patients had a 3.3 times better chance of survival when treated with upfront surgery/PORT versus primary RT/CRT. For HNSCC patients, Slug IHC represents a novel and feasible predictive biomarker to support upfront surgery.

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Aoki, Taku, Takeyuki Watadani, HIroyuki Akai, Yoshihiro Sakamoto, Yasuhiko Sugawara, Kiyoshi Hasegawa, and Norihiro Kokudo. "Results of up-front surgery combined with adjuvant chemotherapy for pancreatic head cancer: Adjuvant gemcitabine chemotherapy may be more effective for borderline resectable cases." Pancreatology 14, no. 3 (June 2014): S110. http://dx.doi.org/10.1016/j.pan.2014.05.751.

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Poultsides, G. A., E. L. Servais, L. B. Saltz, S. Patil, N. E. Kemeny, J. G. Guillem, M. Weiser, L. K. Temple, W. Wong, and P. B. Paty. "Outcome of primary tumor in patients with synchronous stage IV colorectal cancer receiving combination chemotherapy without surgery as initial treatment." Journal of Clinical Oncology 27, no. 18_suppl (June 20, 2009): CRA4030. http://dx.doi.org/10.1200/jco.2009.27.18_suppl.cra4030.

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CRA4030 Background: In the absence of symptoms (bleeding, perforation, obstruction) or resectable metastatic disease, primary tumor resection in patients who present with synchronous metastatic colorectal cancer (CRC) is of uncertain benefit. The purpose of this study was to describe the frequency of intervention necessary to palliate the intact primary tumor in patients who present with synchronous stage IV CRC and receive up-front modern combination chemotherapy without prophylactic surgery. Methods: Using a prospective institutional database, we identified 233 consecutive patients from 2000 through 2006 with synchronous metastatic CRC and an unresected primary tumor who received oxaliplatin- or irinotecan-based, triple-drug chemotherapy (FOLFOX, IFL, or FOLFIRI) with or without bevacizumab as their initial treatment. The incidence of subsequent use of surgery, radiotherapy, and/or endoluminal stenting to manage primary tumor complications was recorded. Results: Of 233 patients, 217 (93%) never required surgical palliation of their primary tumor. Sixteen patients (7%) required emergent surgery for primary tumor obstruction or perforation, 10 patients (4%) required nonoperative intervention (stent or radiotherapy), whereas 213 (89%) never required any direct symptomatic management for their intact primary. Of those, 47 (20%) ultimately underwent elective colon resection at the time of metastasectomy and 8 (3%) during laparotomy for hepatic artery infusion pump placement. Neither use of bevacizumab, location of the primary tumor in the rectum, or metastatic disease burden were associated with increased intervention rate. In addition, when included as a time-varying covariate in a Cox regression model, the need for emergent intervention did not correlate with overall survival. Conclusions: Most patients with synchronous stage IV CRC who receive up-front modern combination chemotherapy never require palliative surgery for their intact primary. These data support the use of chemotherapy, without routine prophylactic resection, as the appropriate standard practice for patients with neither obstructed nor hemorrhaging primary colorectal tumors in the setting of metastatic disease. [Table: see text]

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Poultsides, George A., Elliot L. Servais, Leonard B. Saltz, Sujata Patil, Nancy E. Kemeny, Jose G. Guillem, Martin Weiser, Larissa K. F. Temple, W. Douglas Wong, and Phillip B. Paty. "Outcome of Primary Tumor in Patients With Synchronous Stage IV Colorectal Cancer Receiving Combination Chemotherapy Without Surgery As Initial Treatment." Journal of Clinical Oncology 27, no. 20 (July 10, 2009): 3379–84. http://dx.doi.org/10.1200/jco.2008.20.9817.

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Purpose The purpose of this study was to describe the frequency of interventions necessary to palliate the intact primary tumor in patients who present with synchronous, stage IV colorectal cancer (CRC) and who receive up-front modern combination chemotherapy without prophylactic surgery. Patients and Methods By using a prospective institutional database, we identified 233 consecutive patients from 2000 through 2006 with synchronous metastatic CRC and an unresected primary tumor who received oxaliplatin- or irinotecan-based, triple-drug chemotherapy (infusional fluorouracil, leucovorin, and oxaliplatin; bolus fluorouracil, leucovorin, and irinotecan; or fluorouracil, leucovorin, and irinotecan) with or without bevacizumab as their initial treatment. The incidence of subsequent use of surgery, radiotherapy, and/or endoluminal stenting to manage primary tumor complications was recorded. Results Of 233 patients, 217 (93%) never required surgical palliation of their primary tumor. Sixteen patients (7%) required emergent surgery for primary tumor obstruction or perforation, 10 patients (4%) required nonoperative intervention (ie, stent or radiotherapy), and 213 (89%) never required any direct symptomatic management for their intact primary tumor. Of those 213 patients, 47 patients (20%) ultimately underwent elective colon resection at the time of metastasectomy, and eight patients (3%) underwent this resection during laparotomy for hepatic artery infusion pump placement. Use of bevacizumab, location of the primary tumor in the rectum, and metastatic disease burden were not associated with increased intervention rate. Conclusion Most patients with synchronous, stage IV CRC who receive up-front modern combination chemotherapy never require palliative surgery for their intact primary tumor. These data support the use of chemotherapy, without routine prophylactic resection, as the appropriate standard practice for patients with neither obstructed nor hemorrhaging primary colorectal tumors in the setting of metastatic disease.

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Motoi, Fuyuhiko, and Michiaki Unno. "Adjuvant and neoadjuvant treatment for pancreatic adenocarcinoma." Japanese Journal of Clinical Oncology 50, no. 5 (February 21, 2020): 483–89. http://dx.doi.org/10.1093/jjco/hyaa018.

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Abstract The prognosis of pancreatic adenocarcinoma is dismal. Hence, advances in multidisciplinary treatment strategies, including surgery, are urgently needed. Early recurrence of distant organ metastases suggests that there are occult metastases even in cases with resectable disease. Several randomized controlled trials on adjuvant chemotherapy have been conducted to prolong survival after resection. CONKO-001 study was the first to demonstrate significant improvement in disease-free survival after surgery with gemcitabine administration. The JASPAC-01 study showed the superiority of adjuvant S1 over gemcitabine in survival after resection. Based on the results, adjuvant S1 therapy is the prescribed standard of care in Japan. Recently, the PRODIGE 24/CCTG PA.6 study showed that survival of patients treated with a modified FOLFIRINOX regimen as adjuvant therapy was significantly longer than those treated with adjuvant gemcitabine therapy. Although the evidence from these trials on adjuvant chemotherapy have been the gold-standard treatment for curatively resected and fully recovered patients, resectable disease at diagnosis is not the status, resected disease after curative resection. Currently, neoadjuvant therapy is considered to be a promising alternative to surgery for pancreatic cancer. Although there are many reports regarding neoadjuvant chemoradiotherapy, so far there has been no solid evidence proving the advantage of this strategy versus standard up-front surgery. Newly obtained results from the Prep-02/JSAP05 randomized phase II/III study, comparing neoadjuvant therapy with up-front surgery, revealed significant improvement in overall survival with neoadjuvant chemotherapy by intention-to-treat analysis. Thus, neoadjuvant intervention might become a new standard strategy in cases undergoing planned resection for pancreatic cancer.

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Polcz, Monica, Jesse Smith, and Philip Paty. "Evolving paradigms in locally advanced rectal cancer: Review of the non-operative approach and future directions." Acta chirurgica Iugoslavica 61, no. 2 (2014): 23–29. http://dx.doi.org/10.2298/aci1402023p.

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The standard treatment of locally advanced rectal cancer in the United States is neoadjuvant chemoradiation, surgical resection with total mesorectal excision, and adjuvant chemotherapy. In recent years, a non-operative approach has been suggested for patients achieving a complete clinical response with chemoradiation alone to avoid the morbidity that accompanies radical excision. This approach is justified by the observation that a significant proportion of patients (15-40%) have achieved a pathological complete response by the time of surgery. We review the most recent literature to determine if the oncologic outcomes are comparable. We also discuss future directions in management, including the consolidation of chemotherapy with neoadjuvant chemoradiation. Currently, distant recurrence rates exceed those of local recurrence and adjuvant chemotherapy is often delayed pending post-operative recovery. Offering chemotherapy up-front would simultaneously treat both the primary tumor and any micrometastatic disease without delay. A trial is currently underway at our center evaluating these treatment modalities.

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Canales, Miguel A., Javier de la Serna, Pilar Sabin, Joaquin Diaz-Mediavilla, Mariano Provencio, Rosa Ayala, Ricardo Perez, et al. "Up-Front Treatment of Diffuse Large-B Cell Lymphoma (DLBCL) in Elderly Patients with Rituximab in Combination with CHOP-Like Chemotherapy: A Multicenter Study on the Current Clinical Management." Blood 106, no. 11 (November 16, 2005): 4778. http://dx.doi.org/10.1182/blood.v106.11.4778.4778.

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Abstract Based on results of GELA study, rituximab in combination with CHOP chemotherapy, given for eight cycles, may be considered the new standard of care for patients older than 60 years diagnosed with DLBCL. However, the afraid of early toxicity and underlying co-morbid illness in elderly patients implies often adjustments in this scheme. The aim of this study was to analyze the routine clinical practice in the up-front treatment of elderly patients (>65 years) with DLBCL. We have enrolled onto this study 80 patients (48 females) with median age 74 years (range, 65 to 85 years) who have been treated with CHOP-like regimens in combination with rituximab as first-line therapy. The 75% of patients had ECOG 0-1, 81% had Ann-Arbor stage III-IV, 41% had B-symptoms, 59% had aIPI 2-3, 39% had bulky disease (> 7 cm) and 55% had elevated beta-2 microglobulin. The most of patients received as up-front therapy R-CHOP (89%); R-CNOP and R-CEOP (doxorubicin is substituted for mitoxantrone and epirubicin, respectively) were the alternative regimens administered. The 57.5% of patients received 6 courses of treatment; the 25% received less than 6 cycles and only the 6% of patients (5 out of 80 patients) received 8 courses of treatment. In 31 out of 80 patients the doses of chemotherapy was reduced; in 20 patients the doses of chemotherapy were reduced in all courses and 2 patients received reduced doses of chemotherapy in 5 out of 6 cycles. In the 40% of patients G-CSF have been administered. The overall response rate was 86% (72% CR/CRu, 14% PR). In the 22 patients who received the lower doses of chemotherapy the overall response rate was 82% (50% CR/CRu) versus 88% in the remaining patients (81% CR/CRu) (p<0.05). Adverse events were observed in the 47.5% of patients and neutropenia was the most frequent complication. In those patients who received reduced doses of chemotherapy less adverse events were observed (13.6% versus 60.3%, p<0.001). With a median follow-up of 15 months, the event-free survival in the assessable population has not been reached (60% at 2 years) and there was no significant difference in those patients who have received the reduced doses of chemotherapy (median 18.5 months versus not reached). The median overall survival has not been reached. At 2 years overall survival is 73% in the entire population and 51% in patients receiving the reduced doses of chemotherapy compared to 80% in the remaining patients but the difference was not statistically significant. In conclusion, in our current clinical practice, 6 courses of chemotherapy (CHOP-like) in combination with rituximab is the commonest regimen used for the treatment of elderly patients. The administration of reduced doses of chemotherapy is associated with both a significant decrease in adverse events and complete response rates and may be translated into a shorter event-free and overall survival. A longer follow-up may be necessary to reveal this difference. Logically, randomized trials are mandatory to address differences between 6 and 8 courses of immunochemotherapy in this population.

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Moiseenko, R. A., A. V. Filin, D. G. Akhaladze, S. R. Talypov, M. A. Rakov, E. V. Feoktistova, G. V. Tereshchenko, et al. "Hepatoblastoma relapses after front-line therapy according to SIOPEL protocols: clinical characteristics and outcome." Pediatric Hematology/Oncology and Immunopathology 19, no. 4 (December 22, 2020): 32–44. http://dx.doi.org/10.24287/1726-1708-2020-19-4-32-44.

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Hepatoblastoma (HB) is the most common primary malignant liver tumor in children. Relapses of HB are rare and make up no more than 12% of cases among patients who have achieved complete response after the first-line therapy. The aim of the study was to analyze the incidence, clinical characteristics and outcome of HB relapses in patients treated according to SIOPEL protocols. This study is supported by the Independent Ethics Committee and approved by the Academic Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology. 74 patients with HB were treated for the period 02.2012–12.2018 (82 months). Patients were stratified and treated according to SIOPEL protocols. Relapses were detected in 7/70 (10,0%) patients, who achieved complete response after front-line therapy. We analyzed demographic data, initial tumor characteristics, details of front-line therapy, characteristics of HB relapses and treatment of relapse. Median age at the time of diagnosis of HB was 13,3 (range 0,6–62,9) months. Male:female ratio – 1:0,4. The distribution by PRETEXT stages: II – 2 (28,6%), III – 1 (14,3%), IV – 4 (57,1%). 4 (57,1%) patients had distant metastases. Patients were stratified to standard-risk group – 2 (28,6%) and high-risk group – 5 (71,4%). 3 (42,8%) underwent liver transplantation (LT). Median age at the time of relapse was 33,5 (range 11,9–74,4) months. Median time from the completion of front-line therapy to relapse – 5,3 (range 3,2–19,1) months. Median AFP level at relapse – 35,0 (range 1,8–34160,4) ng/ml. Methods of relapse detection: routine follow-up – 5 (71,4%), clinical symptoms – 2 (28,6%). The latter 2 patients with initially AFP-secreting HB had normal AFP levels at relapse. Pattern of relapse: systemic – 5 (71,4%), combined – 2 (28,6%). The majority of patients received irinotecan-based chemotherapy – 5 (71,4%). Chemotherapy was combined with surgery in 6 (85,7%) cases. Median follow-up time from the moment of relapse was 22,4 (range 5,2–51,3) months. Outcomes: 5 (71,4%) alive (4/5 – with no evidence of disease, 1/5 – with active disease), 2 (28,6%) died of the disease. 3-year overall survival after relapse was 66,6 ± 19,2%. The main conclusion of the study was that combination of second-line chemotherapy with surgical resections allowed achieving long-lasting survival in some HB relapsed patients, including patients who had previously undergone LT.

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Choi, Yunsuk, Sung-Doo Kim, Young-Hoon Park, Jae Seok Lee, Dae-Young Kim, Jung-Hee Lee, Kyoo-Hyung Lee, et al. "Up-Front Allogeneic Hematopoietic Cell Transplantation in Acute Myeloid Leukemia Arising from the Myelodysplastic Syndrome." Acta Haematologica 133, no. 2 (October 11, 2014): 183–92. http://dx.doi.org/10.1159/000362260.

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In patients with secondary acute myeloid leukemia (s-AML) arising from the myelodysplastic syndrome (MDS), treatment outcome is unsatisfactory. We compared up-front allogeneic hematopoietic cell transplantation (HCT) to induction chemotherapy (IC) as an initial treatment in patients with s-AML arising from MDS. This retrospective study included 85 patients who were diagnosed with s-AML arising from MDS; 11 patients proceeded to up-front HCT without IC (HCT group) and 74 received IC (IC group) as an initial treatment for s-AML, 28 of whom subsequently underwent HCT. In the IC group, 41.9% achieved complete remission (CR) compared to 81.8% in the HCT group (p = 0.013). The HCT group showed a significantly longer event-free survival (EFS) than the IC group (median 29.2 vs. 5.2 months, p = 0.042). Overall survival of the HCT group was higher than that of the IC group, but the difference was not statistically significant (median 34.6 vs. 7.6 months, p = 0.149). After adjustment for other clinical factors, outcome in the HCT group was significantly better than in the IC group in terms of CR rate (hazard ratio, HR, 11.195; p = 0.007) and EFS (HR, 0.384; p = 0.029). Up-front HCT is a viable option in s-AML arising from MDS if an appropriate donor is available. © 2014 S. Karger AG, Basel

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Cermak, Jaroslav, Antonin Vitek, Marketa Markova, and Petr Cetkovsky. "Combination Chemotherapy Leading In Advanced MDS Patients to a Rapid Clearence of Bone Marrow Blasts Prior Stem Cell transplantation (SCT) Is Superior to up-Front SCT Even with Intensified Conditioning for Long-Term Survival." Blood 116, no. 21 (November 19, 2010): 4020. http://dx.doi.org/10.1182/blood.v116.21.4020.4020.

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Abstract Abstract 4020 A retrospective analysis of influence of different clinical and laboratory parameters on disease outcome was performed in a cohort of 43 patients with advanced myelodysplasia (MDS)(RAEB > 10% blasts + RAEB-T according to the FAB classification) who underwent allogeneic stem cell transplantation (SCT) in our institute within past 20 years; 21 patients were transplanted with < 10% of bone marrow (BM) blasts after 1 or 2 courses of induction followed by 1 or 2 courses of consolidation chemotherapy (Group A), 22 patients were transplanted with > 10% BM blasts either prior treated with combination chemotherapy or transplanted up-front with intensified conditioning (Group B). Median survival of all transplanted patients was 35,5 months (+/− 53,9 months) with a significant difference between Group A and B (57,5+/−62,3 months v.s. 18,0 +/−36,7 months, p=0.017). Estimated 3 year and 10 year survival for all patients were 53,5% and 41,9%, respectively. Estimated 3 and 10 year survival also significantly differed between Group A and B (71,4% and 57,1% for Group A and 36,4% and 27,3% for Group B). Complete remission (CR) rate was 44,2%, 18,6% patients relapsed (14,3% in Group A and 22,7% in Group B). No difference in overall survival was observed between patients with > 10% BM blasts transplanted either after chemotherapy or up-front (median survival: 26,8+/− 41,4 v.s. 18,0+/−33,8 months, respectively, p=0.65). Univariate analysis using Kaplan-Meier curves and log-rank2 test revealed as significant variables affecting overall survival: achievement of CR (p=0.007), achievement of < 10% BM blasts prior SCT (p=0.011), SCT performed < 4 months after diagnosis (p=0.031) and absence of relapse (p=0.046). Independent variables for determining overall survival (identified by Cox regression multivariate analysis) were: SCT performed < 4 months after dg. (p=0.003,χ2= 8,798), achievement of CR (p=0.011,χ2= 6,457), and age < 50 years (p=0.044,χ2= 4,053). None independent variable determining occurrence of relapse was found. Neither the percentage of BM blasts at the time of dg. and initial transfusion dependency, nor the donor origin (related or unrelated) and number of consolidation courses affected survival. Conclusions: combination chemotherapy leading to a rapid clearance of BM blasts below 10% followed by immediate SCT represented the best treatment option for younger patients with MDS with > 10% BM blasts. Patients transplanted with > 10% BM blasts at the time of conditioning had significantly inferior outcome either transplanted after previous chemotherapy or up-front with intensified conditioning. In this subset of patients, a possible benefit of addition of hypomethylating agents to the treatment schedules prior SCT should be studied. The study was supported by scientific programme MZCR 00023736. Disclosures: No relevant conflicts of interest to declare.

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Kennedy, Vanessa E., Theresa Keegan, Qian Li, Fran Maguire, and Lori S. Muffly. "Treatment Patterns, Type of Front-Line Regimen, and Outcomes Among Older Adults with Acute Myeloid Leukemia: A Population-Based Analysis in the Modern Era." Blood 136, Supplement 1 (November 5, 2020): 15–16. http://dx.doi.org/10.1182/blood-2020-140603.

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Background: Traditionally, intensive induction chemotherapy has been the primary front-line treatment for AML; however, older adults are often poor chemotherapy candidates and as of 2009, nearly 50% of older AML patients did not receive any treatment (Mederios, Ann Hematol 2015). Recently, several non-traditional front-line AML regimens have emerged, including hypomethylating agents (HMA), the BCL-2 inhibitor venetoclax, liposomal anthracycline and cytarabine, and targeted therapies. These non-traditional agents may offer less intense side effects and provide novel front-line options for older adults. We hypothesized the advent of non-traditional options has allowed a greater proportion of older adults to receive effective treatment, thereby improving survival for this population. Using a population-based approach, we evaluated front-line treatment patterns and outcomes of older adults with AML in the modern era. Methods: Patients ≥ 60 years with a first diagnosis of AML in the California Cancer Registry (CCR) between 2014-2017 were included. Front-line regimen was manually abstracted from unstructured free-text fields in the CCR. The CCR was linked with California's Patient Discharge Database (PDD) to obtain hematopoietic cell transplantation (HCT) information. Multivariable logistic regression examined factors associated with front-line treatment regimen and multivariable Cox proportional hazards regression examined factors associated with survival. Results: Of the 4,086 patients identified, 3,068 (75%) had sufficient treatment information to classify front-line regimen and are included; 34% were 60-69 years at diagnosis, 39% were 70-79, and 27% were ≥ 80. Thirty-three percent received front-line therapy at an NCI-designated cancer center and 12% received HCT. The median follow-up time was 121 days. Across the time period studied, 36% received traditional cytotoxic chemotherapy, 42% received non-traditional therapy, and 22% received no treatment. Of the patients receiving traditional therapy, 84% received cytarabine plus anthracycline. Of those receiving non-traditional therapy, 85% received HMA monotherapy, 8% HMA plus venetoclax, and 3% liposomal cytarabine plus anthracycline. Use of both non-traditional therapy and HCT increased over time, with 38% of patients receiving non-traditional therapy in 2014 vs 47% in 2017 (p < 0.001) and 8.4% of patients receiving HCT in 2014 compared to 11.1% in 2017 (p < 0.001.) The proportion of patients not receiving treatment did not change significantly over time, with 23% in 2014 vs 24% in 2017 (p = 0.20). Multivariable analyses (MVA) revealed receipt of treatment was significantly associated with age < 80 (p < 0.001), < 2 comorbidities (p < 0.001), and receipt of front-line therapy at an NCI-designated cancer center (p < 0.001). Compared to traditional chemotherapy, non-traditional frontline therapy was associated with age ≥ 80 (p < 0.001) and ≥ 2 comorbidities (p = 0.001). Race/ethnicity, socioeconomic status, and type of insurance were not associated with receipt of treatment or type of front-line regimen. One-year overall survival (OS) of the full cohort was 25% (CI: 23.6 - 26.5%). One-year OS was 44% (CI: 40.8 - 47.1%) for patients receiving traditional chemotherapy, 31.4% (CI: 40.8 - 47.13%) for patients receiving non-traditional therapy, and 4.38% (CI: 2.73 - 6.04%) for patients who were not treated. The MVA for OS demonstrated age ≥ 80 (HR 1.19, CI 1.04 - 1.36), ≥ 2 comorbidities (HR 1.33, CI 1.19 - 1.49), and not receiving front-line therapy at an NCI cancer center (HR 1.49, CI 1.34 - 1.65) to be independently associated with inferior OS; receipt of traditional chemotherapy (HR 0.22, CI 0.19 - 0.25) and HCT (HR 0.75, CI 0.6 - 0.93) were associated with superior OS. Conclusion Using a population-based approach, we show the patterns of care for AML treatment in older adults is changing, with an increasing proportion of patients receiving both initial treatment and HCT relative to historical reports and a significant increase in the use of newer, non-traditional therapies. Similarly, survival estimates are improving over time for patients who receive therapy. During our study period, a significant proportion of older adults with AML remain untreated, which is strikingly impacted by location of front-line care. At the population level, there remain opportunities to increase access to therapy for older adults with AML. Disclosures Muffly: Amgen: Consultancy; Servier: Research Funding; Adaptive: Research Funding.

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Hu, Jiong, Yuan-Fang Liu, Yong-Mei Zhu, Zhan-Zhong Shi, Jun-Min Li, Li Wang, Yu Chen, and Zhi-Xiang Shen. "A 3-Year Follow-Up of All-Trans Retinoic Acid (ATRA) and Arsenic Trioxide (As2O3) as Front Line Therapy for Newly Diagnosed Acute Promyelocytic Leukemia (APL)." Blood 106, no. 11 (November 16, 2005): 886. http://dx.doi.org/10.1182/blood.v106.11.886.886.

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Abstract PURPOSE: To confirm the potential benefit of front-line use of all-trans retinoic acid (ATRA) combined with arsenic trioxide (As2O3) in patients with newly diagnosed acute promyelocytic leukemia (APL) with prolonged follow-up to median of 3-year and compared with historical control. PATIENTS AND METHODS: Two groups of newly diagnosed patients with APL were included in the analysis. The study group received combination therapy of ATRA and As2O3 includes 56 patients since April 2001. The historical control groups included 56 patients from May 1998 to March 2001. No statistically significant differences of clinical characteristics such as sex, age and hematological data were documented between two groups. For the study group groups, all patients received 25mg/m2 ATRA orally and 0.16mg/kg As2O3 intravenously per day till CR. Once CR achieved, they were given 3 courses of consolidation chemotherapy and then 5 cycles of sequential treatment of ATRA, As2O3 and 6-MP/MTX. For the historical group, the induction therapy was ATRA given at 25mg/m2 daily till CR and chemotherapy was added in case of leukocytosis. The post-remission therapy consists of chemotherapy with ATRA. RESULT: In study group, 52 (92.9%) patients achieved CR and the time to CR was 26.4±4.5 days. At last follow-up at February 2005, only two patients underwent extramedullary relapse and one died from CNS leukemia while all other patients were alive and remained in hematological remission. With a median follow-up of 34 months (21 to 46 months), the 3-year OS and EFS were estimated as 97.4% and 93.5%. For the historical control groups, the median follow-up was 56 months (12 to 79 months). The 3-year estimated OS and EFS was 83.2% and 57.7% (P=0.069 and 0.00001 respectively). Of notice, in the last follow-up, all evaluable patients in clinical remission maintained a complete molecular response (undetectable PML-RARa via both regular and real-time RT-PCR). CONCLUSION: Our 3-year follow-up data demonstrate a solid clinical benefit of front-line combination of ATRA and As2O3 in terms of EFS. There was also a trend toward improvement in OS which might translate into better chance of curing the disease.

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Dizon, Don S., Martee L. Hensley, Elizabeth A. Poynor, Paul Sabbatini, Carol Aghajanian, Amanda Hummer, Ennapadam Venkatraman, and David R. Spriggs. "Retrospective Analysis of Carboplatin and Paclitaxel as Initial Second-Line Therapy for Recurrent Epithelial Ovarian Carcinoma: Application Toward a Dynamic Disease State Model of Ovarian Cancer." Journal of Clinical Oncology 20, no. 5 (March 1, 2002): 1238–47. http://dx.doi.org/10.1200/jco.2002.20.5.1238.

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PURPOSE: The majority of patients with epithelial ovarian cancer (EOC) who achieve a complete remission with front-line chemotherapy develop recurrent disease. Carboplatin and paclitaxel are used for patients with platinum-sensitive recurrent disease, although there is little information regarding the response and survival in unselected patients treated with this strategy. We sought to determine the outcomes for patients with EOC treated with carboplatin and paclitaxel at the time of first recurrence. In addition, we sought to define a new paradigm for disease transition in patients with EOC. PATIENTS AND METHODS: Eighty-nine patients were identified who had a complete response to front-line platinum-based chemotherapy for EOC, relapsed 6 months after completion of front-line chemotherapy, and were treated with carboplatin and paclitaxel as second-line therapy. RESULTS: Eighty-four cases were available for analysis of survival end points, and 66 were assessable for response. The median follow-up was 27 months. The overall response rate was 70%. The median progression-free interval for the cohort was 13 months (95% confidence interval [CI], 10.7 to 13.8 months). The 3-year survival rate was 72% (95% CI, 59.4 to 86.1%). Toxicity was limited, and no deaths from treatment were observed. Using this data, it is possible to construct a disease states model of EOC, which provides risk estimates for transitions between clinically distinct categories. CONCLUSION: Re-treatment with carboplatin and paclitaxel is effective as initial therapy in recurrent EOC. This should form the basis of a randomized trial to determine the best agents for initial treatment of relapse from EOC in potentially platinum-sensitive patients.

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Bush, Nancy Ann Oberheim, Jacob S. Young, Yalan Zhang, Cecilia L. Dalle Ore, Annette M. Molinaro, Jennie Taylor, Jennifer Clarke, et al. "A single institution retrospective analysis on survival based on treatment paradigms for patients with anaplastic oligodendroglioma." Journal of Neuro-Oncology 153, no. 3 (June 14, 2021): 447–54. http://dx.doi.org/10.1007/s11060-021-03781-z.

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Abstract Introduction Anaplastic oligodendrogliomas are high-grade gliomas defined molecularly by 1p19q co-deletion. There is no curative therapy, and standard of care includes surgical resection followed by radiation and chemotherapy. However, the benefit of up-front radiation with chemotherapy compared to chemotherapy alone has not been demonstrated in a randomized control trial. Given the potential long-term consequences of radiation therapy, such as cognitive impairment, arteriopathy, endocrinopathy, and hearing/visual impairment, there is an effort to balance longevity with radiation toxicity. Methods We performed a retrospective single institution analysis of survival of patients with anaplastic oligodendroglioma over 20 years. Results 159 patients were identified as diagnosed with an anaplastic oligodendroglioma between 1996 and 2016. Of those, 40 patients were found to have AO at original diagnosis and had documented 1p19q co-deletion with a median of 7.1 years of follow-up (range: 0.6–16.7 years). After surgery, 45 % of patients were treated with radiation and chemotherapy at diagnosis, and 50 % were treated with adjuvant chemotherapy alone. The group treated with chemotherapy alone had a trend of receiving more cycles of chemotherapy than patients treated with radiation and chemotherapy upfront (p = 0.051). Median overall survival has not yet been reached. The related risk of progression in the upfront, adjuvant chemotherapy only group was almost 5-fold higher than the patients who received radiation and chemotherapy (hazard ratio = 4.85 (1.74–13.49), p = 0.002). However, there was no significant difference in overall survival in patients treated with upfront chemotherapy compared to patients treated upfront with chemotherapy and radiation (p = 0.8). Univariate analysis of age, KPS, extent of resection, or upfront versus delayed radiation was not associated with improved survival. Conclusions Initial treatment with adjuvant chemotherapy alone, rather than radiation and chemotherapy, may be an option for some patients with anaplastic oligodendroglioma, as it is associated with similar overall survival despite shorter progression free survival.

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Corradini, P., C. Tarella, F. Zallio, A. Dodero, M. Zanni, P. Valagussa, A. M. Gianni, A. Rambaldi, T. Barbui, and S. Cortelazzo. "Long-term follow-up of patients with peripheral T-cell lymphomas treated up-front with high-dose chemotherapy followed by autologous stem cell transplantation." Leukemia 20, no. 9 (July 27, 2006): 1533–38. http://dx.doi.org/10.1038/sj.leu.2404306.

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Martelli, Maurizio, Filippo Gherlinzoni, Amalia De Renzo, Pier Luigi Zinzani, Antonio De Vivo, Maria Cantonetti, Brunangelo Falini, et al. "Early Autologous Stem-Cell Transplantation Versus Conventional Chemotherapy as Front-Line Therapy in High-Risk, Aggressive Non-Hodgkin’s Lymphoma: An Italian Multicenter Randomized Trial." Journal of Clinical Oncology 21, no. 7 (April 1, 2003): 1255–62. http://dx.doi.org/10.1200/jco.2003.01.117.

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Purpose: To evaluate the role of early intensification with high-dose therapy (HDT) and autologous stem-cell transplantation (ASCT) as front-line chemotherapy for patients with high-risk, histologically aggressive non-Hodgkin’s lymphoma (NHL). Patients and Methods: We planned a multicenter, randomized trial to compare a conventional chemotherapy regimen of methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B; arm A) with an abbreviated regimen of MACOP-B (8 weeks) followed by HDT and ASCT (arm B) for intermediate-high-risk/high-risk patients (according to the age-adjusted International Prognostic Index). From September 1994 to April 1998, 150 patients with aggressive lymphoma were enrolled onto the trial. Seventy-five patients were randomly assigned to arm A and 75 patients were randomly assigned to arm B. In both arms, involved-field radiation therapy (36 Gy) was delivered to the site of bulky disease. Results: The rate of complete response was 68% in arm A and 76% in arm B (P = not significant [NS]). Three toxic deaths (4%) occurred in arm B and one (1%) occurred in arm A (P = NS). In arm B, 30 patients (40%) did not undergo HDT and ASCT. According to the intention-to-treat analysis at a median follow-up of 24 months, 5-year overall survival probability in arms A and B was 65% and 64% (P = .95), 5-year progression-free survival was 49% and 61% (P = .21), and 5-year relapse-free survival was 65% and 77% (P = .22), respectively. Conclusion: Abbreviated chemotherapy followed by intensification with HDT-ASCT is not superior to conventional chemotherapy in patients with high-risk, aggressive NHL. Additional randomized trials will clarify whether HDT-ASCT as front-line therapy after a complete course of conventional chemotherapy improves survival in this group of patients.

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Frenay, M., C. Lebrun, M. Lonjon, P. Y. Bondiau, and M. Chatel. "Up-front chemotherapy with fotemustine (F)/cisplatin (CDDP)/etoposide (VP16) regimen in the treatment of 33 non-removable glioblastomas." European Journal of Cancer 36, no. 8 (May 2000): 1026–31. http://dx.doi.org/10.1016/s0959-8049(00)00048-4.

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Ma, Wei-Li, Chia-Chi Lin, Feng-Ming Hsu, Jang-Ming Lee, Jin-Shing Chen, Min-Shu Hsieh, Yih-Leong Chang, Ying-Ting Chao, Chin-Hao Chang, and James Chih-Hsin Yang. "Clinical Outcomes of Up-front Surgery Versus Surgery After Induction Chemotherapy for Thymoma and Thymic Carcinoma: A Retrospective Study." Clinical Lung Cancer 20, no. 6 (November 2019): e609-e618. http://dx.doi.org/10.1016/j.cllc.2019.06.011.

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