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Journal articles on the topic 'Dose intensity'

Author: Grafiati

Published: 9 March 2023

Last updated: 22 June 2025

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1

Ozols, R. F., J. T. Thigpen, J. Dauplat, et al. "Dose intensity." Annals of Oncology 4 (1993): S49—S56. http://dx.doi.org/10.1093/annonc/4.suppl_4.s49.

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2

SURBONE, ANTONELLA, and VINCENT T. DeVITA. "Dose Intensity." Annals of the New York Academy of Sciences 698, no. 1 Breast Cancer (1993): 279–88. http://dx.doi.org/10.1111/j.1749-6632.1993.tb17219.x.

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3

Coldman, A. J., and C. M. Coppin. "Calculating dose intensity." Journal of Clinical Oncology 9, no. 9 (1991): 1713–14. http://dx.doi.org/10.1200/jco.1991.9.9.1713.

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4

Piccart, M. J., L. Biganzoli, and A. Di Leo. "S34 Dose intensity and dose density." European Journal of Cancer 34 (February 1998): S8. http://dx.doi.org/10.1016/s0959-8049(97)89207-6.

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5

Portlock, C. S. "Dose density and dose intensity: where does CHOP go from here?" Annals of Oncology 13, no. 9 (2002): 1329–30. http://dx.doi.org/10.1093/annonc/mdf238.

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6

Tonkin, Katia, and Ian Tannock. "Dose Intensity in Chemotherapy." Journal of Clinical Oncology 3, no. 6 (1985): 891. http://dx.doi.org/10.1200/jco.1985.3.6.891.

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To the Editor: In a recent article, Hryniuk and Bush have established a strong correlation between dose intensity of CMF (cyclophosphamide, methotrexate, 5-fluorouracil) chemotherapy, and the rate of tumor response in patients with metastatic breast cancer. They also observed a significant correlation between rate of tumor response and median survival time (r = .66, P < .001). The authors were careful to avoid the conclusion that there was a direct correlation between dose intensity and median survival, but it is surprising that they did not examine this more important relationship directly. We have used data provided in their paper to test for correlation between median survival time and dose intensity for patients receiving CMF chemotherapy, and find little evidence for a direct relationship (r = .25, P = .27—two-tailed Student's t test). Moreover, if the studies are weighted according to the number of patients in them, the correlation coefficient is even lower (r = .14, P = .50—two-tailed Student's t test). Unfortunately, metastatic breast cancer is not cured by chemotherapy, and appropriate endpoints are those of palliation, namely quantity and quality of survival. Quality of survival cannot easily be addressed in a retrospective review, but increasing dose intensity has the capability both to improve quality of life by ameliorating symptoms of disease, and to decrease it by adding toxicity. Factors such as sites of metastases and performance status of patients are known to influence duration of survival and could mask a relationship with dose intensity. However, the data reviewed by Hryniuk and Bush do not provide evidence for a relationship between dose of chemotherapy and survival. A prospective randomized trial is in progress at our institution that addresses the relationship between dose intensity of CMF chemotherapy and both quantity and quality of survival for patients with metastatic breast cancer. In the absence of results from this and other prospective trials that address the dose-response effect of chemotherapy in palliation, one should not assume that more is better.

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7

Hryniak, William. "Dose Intensity…and Beyond." Cancer Investigation 22, no. 4 (2004): 648–49. http://dx.doi.org/10.1081/cnv-200027172.

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8

Meyer, R., M. Goodyear, and W. Hryniuk. "Dose intensity and lymphoma." Journal of Clinical Oncology 9, no. 8 (1991): 1511. http://dx.doi.org/10.1200/jco.1991.9.8.1511.

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9

Coldman, Andrew J., Christopher M. L. Coppin, and James H. Goldie. "Models for dose intensity." Mathematical Biosciences 92, no. 1 (1988): 97–113. http://dx.doi.org/10.1016/0025-5564(88)90007-7.

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10

Gianni, A. M., and M. J. Piccart. "Optimising chemotherapy dose density and dose intensity." European Journal of Cancer 36 (April 2000): 1–3. http://dx.doi.org/10.1016/s0959-8049(99)00258-0.

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11

Warde, Nick. "Does the dose intensity of BEP chemotherapy affect survival?" Nature Reviews Urology 7, no. 9 (2010): 477. http://dx.doi.org/10.1038/nrurol.2010.127.

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12

Dodwell, DJ, H. Gurney, and N. Thatcher. "Dose intensity in cancer chemotherapy." British Journal of Cancer 61, no. 6 (1990): 789–94. http://dx.doi.org/10.1038/bjc.1990.178.

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13

Cavaletti, G., L. Marzorati, G. Bogliun, et al. "Cisplatin-lnduced peripheral neurotoxicity is dependent on total-dose intensity and single-dose intensity." Cancer 69, no. 1 (1992): 203–7. http://dx.doi.org/10.1002/1097-0142(19920101)69:1<203::aid-cncr2820690133>3.0.co;2-1.

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14

Costabel, U., SD Nathan, L. Lancaster, et al. "Dose modifications and dose intensity during treatment with pirfenidone." Pneumologie 71, S 01 (2017): S1—S125. http://dx.doi.org/10.1055/s-0037-1598499.

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15

Livingston, Robert B. "Dose intensity and high dose therapy. Two different concepts." Cancer 74, S3 (1994): 1177–83. http://dx.doi.org/10.1002/1097-0142(19940801)74:3+<1177::aid-cncr2820741529>3.0.co;2-7.

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16

Levin, L., and W. M. Hryniuk. "Dose intensity analysis of chemotherapy regimens in ovarian carcinoma." Journal of Clinical Oncology 5, no. 5 (1987): 756–67. http://dx.doi.org/10.1200/jco.1987.5.5.756.

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The relationship between outcome and dose intensity was analyzed for first-line chemotherapy of advanced ovarian cancer using a particular CHAP (cyclophosphamide, hexamethylmelamine, Adriamycin [Adria Laboratories, Columbus, OH], cisplatin) regimen as the standard. Previously described techniques were used to calculate the average dose intensity of regimens containing one, two, three, or all four drugs of CHAP, relative to the standard. The average relative dose intensity, especially the relative dose intensity of cisplatin, correlated significantly with clinical response and with median survival time (MST) of the entire group (not just the remitters). There was a distinct advantage for multiagent regimens over single alkylating agents and especially for multiagent regimens containing cisplatin. Survival correlated with response rate (of multiagent regimens). This analysis suggests that dose intensity is a determinant of treatment outcome. Prospective randomized trials would be required to test whether, and to what extent, dose intensity determines outcome independently of total amount of drug given, performance status, or other factors. If dose intensity does determine outcome, methods of increasing it should be tested in an attempt to improve treatment results.

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17

Winkelman, Chris, Abdus Sattar, Hasina Momotaz, et al. "Dose of Early Therapeutic Mobility: Does Frequency or Intensity Matter?" Biological Research For Nursing 20, no. 5 (2018): 522–30. http://dx.doi.org/10.1177/1099800418780492.

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Objective: Investigate the feasibility of a nurse-led mobility protocol and compare the effects of once- versus twice-daily episodes of early therapeutic mobility (ETM) and low- versus moderate-intensity ETM on serum biomarkers of inflammation and selected outcomes in critically ill adults. Design: Randomized interventional study with repeated measures and blinded assessment of outcomes. Setting: Four adult intensive care units (ICUs) in two academic medical centers. Subjects: Fifty-four patients with > 48 hr of mechanical ventilation (MV). Intervention: Patients were assigned to once- or twice-daily ETM via sealed envelope randomization at enrollment. Intensity of (in-bed vs. out-of-bed) ETM was administered according to protocolized patient assessment. Measurements: Interleukins 6, 10, 8, 15, and tumor necrosis factor-α were collected from serum before and after ETM; change scores were used in the analyses. Manual muscle and handgrip strength, delirium onset, duration of MV, and ICU length of stay (LOS) were evaluated as patient outcomes. Main Results: Hypotheses regarding the inflammatory biomarkers were not supported based on confidence intervals. Twice-daily intervention was associated with reduced ICU LOS. Moderate-intensity (out-of-bed) ETM was associated with greater manual muscle test scores and handgrip strength and reduced occurrence of delirium. Conclusion: Findings from this study suggest that nurses can provide twice-daily mobility interventions that include sitting on the edge of the bed once patients have a stable status without altering a pro-inflammatory serum biomarker profile.

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18

Band, Pierre R., Michele Deschamps, and Lucien Israël. "Retinoid Chemoprevention Timing and Dose Intensity." Cancer Investigation 7, no. 2 (1989): 205–10. http://dx.doi.org/10.3109/07357908909038286.

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19

Cohen, M. H. "What determines actual chemotherapy dose intensity?" Journal of Clinical Oncology 8, no. 11 (1990): 1926. http://dx.doi.org/10.1200/jco.1990.8.11.1926.

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20

Hryniuk, W. M., and M. Goodyear. "The calculation of received dose intensity." Journal of Clinical Oncology 8, no. 12 (1990): 1935–37. http://dx.doi.org/10.1200/jco.1990.8.12.1935.

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21

Heller, G., and N. K. Cheung. "Dose-intensity analysis and randomized trials." Journal of Clinical Oncology 9, no. 9 (1991): 1715–16. http://dx.doi.org/10.1200/jco.1991.9.9.1715.

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22

Ozols, Robert F. "Ovarian Cancer: Is Dose Intensity Dead?" Journal of Clinical Oncology 25, no. 27 (2007): 4157–58. http://dx.doi.org/10.1200/jco.2007.12.1723.

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23

Cox, J., D. Ball, C. Belani, et al. "Dose intensity in lung cancer treatment." Lung Cancer 10 (March 1994): S11—S13. http://dx.doi.org/10.1016/0169-5002(94)91661-6.

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24

Sanchis-Gomar, Fabian, Carmen Fiuza-Luces, and Alejandro Lucia. "Exercise Intensity, Dose, and Cardiovascular Disease." JAMA 315, no. 15 (2016): 1658. http://dx.doi.org/10.1001/jama.2016.0306.

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25

Gregory, S. A., and L. Trümper. "Chemotherapy dose intensity in non-Hodgkin's lymphoma: is dose intensity an emerging paradigm for better outcomes?" Annals of Oncology 16, no. 9 (2005): 1413–24. http://dx.doi.org/10.1093/annonc/mdi264.

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26

Simon, R., and E. L. Korn. "Selecting Drug Combinations Based on Total Equivalent Dose (Dose Intensity)." JNCI Journal of the National Cancer Institute 82, no. 18 (1990): 1469–76. http://dx.doi.org/10.1093/jnci/82.18.1469.

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27

Hryniuk, W., E. Frei, and F. A. Wright. "A single scale for comparing dose-intensity of all chemotherapy regimens in breast cancer: summation dose-intensity." Journal of Clinical Oncology 16, no. 9 (1998): 3137–47. http://dx.doi.org/10.1200/jco.1998.16.9.3137.

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PURPOSE To construct a single scale for comparing the dose-intensity of all chemotherapy regimens in breast cancer. MATERIALS AND METHODS First-line single-agent trials in metastatic disease were reviewed. The unit dose-intensity (UDI) that was required to produce a 30% complete response plus partial response (CR + PR) rate was determined for each drug. Randomized trials were then analyzed that prospectively tested dose-intensity. The dose-intensities of the drugs in each arm were expressed as fractions of their UDIs and added together. This yielded each arm's summation dose-intensity (SDI), which was then correlated with treatment outcomes. RESULTS In the single-agent trials, dose-response relationships were linear when the studies covered a range of dose-intensities. In the randomized trials that tested dose-intensity in metastatic disease, response rates and median survival correlated linearly with the SDIs of the treatment arms. An increment of one SDI unit increased CR + PR rate by approximately 30%, CR rate by 10%, and median survival by 3.75 months. Metastatic disease trials were negative if the difference between the arms was less than 0.54 SDI units. Adjuvant trials that tested a dose-intensity difference of less than 0.65 SDI units were also negative. CONCLUSION A single-agent dose-response database can be derived from historic literature that enables comparison of the dose-intensity of all combination regimens on one scale. The dose-intensity increase required to improve outcome can then be identified in earlier trials that tested that variable. SDI methodology should be tested prospectively in contemporary patients, and may be useful in guiding dosage increases beyond the conventional range.

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28

Zelinskiy, A. S., G. A. Yakovlev та D. E. Fil’trov. "Связь мощности дозы гамма-излучения с интенсивностью ливневых осадков". Вестник КРАУНЦ. Физико-математические науки, № 3 (22 листопада 2021): 189–99. http://dx.doi.org/10.26117/2079-6641-2021-36-3-189-199.

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Experimental and theoretical studies of the influence of the intensity, amount and duration of liquid atmospheric precipitation on the formation of γ-background in the surface layer of the atmosphere are presented. It was observed that precipitation causes an increase in the γ-radiation dose rate in the form of bursts. In this case, the total amount of precipitation in an event determines the magnitude of the burst of the dose rate, and the intensity of precipitation determines the rate of increase in the dose rate of γ-radiation. A mathematical model, which establishes a quantitative relationship between the dose rate of γ-radiation and the intensity (amount) of liquid atmospheric precipitation has been developed and verified (R2 = 0.93). Представлены экспериментальные и теоретические исследования влияния интенсивности, количества и продолжительности жидких атмосферных осадков на формирование γ-фона в приземном слое атмосферы. Было замечено, что осадки вызывают увеличение мощности дозы γ-излучения в виде всплесков. В этом случае общее количество осадков в событии определяет величину всплеска мощности дозы, а интенсивность осадков определяет скорость увеличения мощности дозы γ-излучения. Разработана и проверена математическая модель, устанавливающая количественную связь между мощностью дозы γ-излучения и интенсивностью (количеством) жидких атмосферных осадков (R2 = 0,93).

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29

Campbell, Patrick G., Ian B. Stewart, Anita C. Sirotic, and Geoffrey M. Minett. "Does exercise intensity affect wellness scores in a dose-like fashion?" European Journal of Sport Science 20, no. 10 (2020): 1395–404. http://dx.doi.org/10.1080/17461391.2019.1710264.

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30

Alghamdi, Mohammed Abdullah, Richard Lee-Ying, Mina Swiha, et al. "The effect of sorafenib (S) starting dose and dose intensity on survival in patients with advanced hepatocellular carcinoma (HCC)." Journal of Clinical Oncology 35, no. 4_suppl (2017): 400. http://dx.doi.org/10.1200/jco.2017.35.4_suppl.400.

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400 Background: The SHARP trial showed that S improves survival in advanced HCC. In clinical practice full dose (FD) of S at 400mg bid can be difficult to tolerate and so a reduced dose (RD) is often required. The purpose of this study was to determine whether starting dose or dose intensity of S affects survival in patients with HCC. Methods: All patients treated with S for HCC in Alberta, Canada from January 2008 to July 2016 were included in this study. Patient demographics, clinical, tumor characteristics, S starting dose and dose intensity were collected and analyzed. Patients were dichotomized into starting FD or RD of S. A mean dose intensity of > 75% and < / = 75% were considered normal and reduced, respectively. Survival outcomes were assessed with Kaplan-Meier curves and compared with the log-rank test. A Cox-proportional hazard model was constructed with starting dose, dose intensity and relevant clinical and pathologic factors to assess their impact on survival. Results: A total of 156 patients were included. Median age was 63, 78% were men, 34% were East Asian, 77% were Childs-Pugh A, and the most common causes of liver disease were hepatitis B (30%) and C (30%). Most patients had EGOG performance status of 0 and 1 prior to starting S (29% and 62%, respectively). S was started at FD in 58% of patients and 50% had a dose intensity > 75%. The median survival for both starting FD and RD was 10.3 months, and not significantly different (p = 0.14).The median survival for a dose intensity > 75% vs < / = 75% was 10.7 vs 9.5 months, respectively (p = 0.76). In multivariable models that adjusted for demographic, stage, performance status and liver function, starting dose (HR 0.8 95%CI 0.5-1.2) and dose intensity (HR0.9 95% CI 0.6-1.4) were not associated with survival. Conclusions: Starting S with a RD may be a reasonable strategy for HCC, since it does not appear to impact survival. Also, dose intensity did not impact survival, suggesting that additional dose modifications may not compromise effectiveness. Though limited by small numbers, we are planning to confirm these findings in a larger, pan-Canadian dataset.

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31

Lutfi, Forat, Rohit Boshnoi, Vikas Patel, et al. "Bleeding and Thrombotic Risk in Low Dose Heparin Infusion As Compared to Standard Dose Heparin Infusion." Blood 132, Supplement 1 (2018): 1251. http://dx.doi.org/10.1182/blood-2018-99-110232.

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Abstract Introduction: At our institution, therapeutic use of unfractionated heparin (UFH) is administered by standard (target anti-Xa activity level 0.30 to 0.70 IU/mL) and low intensity (target anti-Xa activity level 0.25 to 0.35 IU/mL) protocols. In patients deemed high-risk for hemorrhage, the low intensity protocol is often employed. However, to date, there has been little study of differences in adverse events, namely hemorrhage, and efficacy between intensity protocols. Furthermore, identifying the effect of patient specific factors (e.g. age, indication for UFH, anticoagulant and antiplatelet use, medical, and surgical history) on outcomes has the potential to assist in determining the most optimal protocol. Methods: A total of 377 adult patients receiving therapeutic UFH from July 2011 to July 2017 at a single institution were retrospectively studied. Patients receiving UFH by acute coronary syndrome protocol and those receiving thrombolytics were excluded. IRB approval was obtained prior to collection of data. Results: Of the 377 patients, 42.0% (158/377) and 58.0% (219/377) were on low and standard intensity protocols, respectively. The majority of patients 76.1% (287/377) received an initial bolus. Patients were predominately Caucasian 74.0% (279/377), with median age of 63 years-old, and near equal gender distribution. The main indications for therapeutic UFH were venous thromboembolism VTE 46.9% (177/377) and atrial fibrillation 18.6% (70/377.) The indication for UFH was comparable between both groups with the exception of a higher percentage of those on full intensity protocol being treated for VTE (53.4% vs 38.0%.) Many patients were on home antiplatelet 35.0% (132/377) and anticoagulant 33.2% (125/377) therapy. The percentage of patients on aspirin, antiplatelet, and injectable anticoagulants was similar in both groups. A higher percentage of patients on low intensity protocol were on oral anticoagulants (36.1% vs 24.2%.) The median HAS-BLED score was two in both groups. Low intensity protocol patients were more likely to have had a history of previous bleeding (24.1% vs 12.8%) and had higher incidence of bleeding (10.8% vs 7.8%) than patients receiving standard intensity protocol. Transfusion requirement was greater in the low intensity protocol (29.7% vs 16.4%.) Both groups had similar risk of developing new thrombi (3.2% vs 3.7%) during the study period. All-cause mortality at three-months was higher in the low intensity group (19.6% vs 15.1%.) However, only 3.1% (2/64) of deaths within three-months were due to hemorrhage while on UFH and both were on the standard intensity protocol. Conclusion: Low intensity UFH infusion is used in patients in whom there is clinical concern for increased risk of bleeding. Bleeding rates with both low and standard intensity protocols was comparable (10.8% vs 7.8%), although patients on the low intensity protocol had notably higher transfusion rates (29.7% vs 16.4%.) Rates of new or worsening thrombi were comparable (3.2% vs 3.7%.) Initial analysis of our data suggests that there is not a clinically significant difference in studied outcomes between standard and low intensity protocols. Furthermore, in patients where this is high clinical risk of bleeding, a low intensity protocol can be utilized with similar therapeutic efficacy as a standard intensity protocol. Table Table. Disclosures No relevant conflicts of interest to declare.

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32

Leavey, Patrick J., Elpis Mantadakis, and Gerhard Maale. "VARIABILITY IN DOSE INTENSITY OF HIGH-DOSE METHOTREXATE FOR NONMETASTATIC OSTEOSARCOMA." Pediatric Hematology and Oncology 19, no. 7 (2002): 483–89. http://dx.doi.org/10.1080/08880010290097305.

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33

Dembo, A. J. "Time-dose factors in chemotherapy: expanding the concept of dose-intensity." Journal of Clinical Oncology 5, no. 5 (1987): 694–96. http://dx.doi.org/10.1200/jco.1987.5.5.694.

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34

Meyer, R. M., W. M. Hryniuk, and M. D. Goodyear. "The role of dose intensity in determining outcome in intermediate-grade non-Hodgkin's lymphoma." Journal of Clinical Oncology 9, no. 2 (1991): 339–47. http://dx.doi.org/10.1200/jco.1991.9.2.339.

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To determine whether the dose intensity of chemotherapeutic regimens correlates with the complete remission rate in adult patients with advanced-stage intermediate-grade lymphoma, reports of comparative trials of therapy were reviewed. Reports were identified using MEDLINE, through references from review articles, and through review of selected abstracts. Twenty-two studies including 14 randomized and eight cohort trials were analyzed to assess projected dose intensity. Four other studies were analyzed to assess the role of received dose intensity. Dose intensities were calculated using described methods and correlated with complete remission rates. Individual trials were assessed using "levels of evidence." A metaanalysis of randomized trials and a cross-trial analysis of all comparative trials using a weighted least squares linear regression were performed. Using levels of evidence, support was obtained for the hypothesis that dose intensity correlates with the remission rate from two trials in which dose intensity was "indirectly" tested. As these studies did not "directly" test dose intensity, confounding variables, including those arising from the assumptions made in calculating dose intensity, cannot be excluded. Metaanalysis showed a relative probability of achieving complete remission of 1.34 (95% confidence interval, 1.13 to 1.58) favoring the pooled arm of high dose intensity. Cross-trial analysis showed a relatively weak association between dose intensity and remission rate (r = .49, P = .0001). Two of four reports retrospectively assessing received dose intensity suggested that increased dose intensity is associated with superior remission rates. These analyses suggest that dose intensity may correlate with the remission rate in advanced-stage intermediate-grade lymphoma. However, properly designed trials directly testing dose intensity have not been performed and are needed to confirm this hypothesis.

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35

Jensen, Randy L., Merideth M. Wendland, Shyh-Shi Chern, and Dennis C. Shrieve. "NOVALIS INTENSITY-MODULATED RADIOSURGERY." Neurosurgery 62, suppl_5 (2008): A2—A10. http://dx.doi.org/10.1227/01.neu.0000325931.26531.45.

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ABSTRACT OBJECTIVE The Novalis stereotactic radiotherapy system (BrainLAB, Heimstetten, Germany) allows for precise treatment of cranial base tumors with single-fraction radiosurgery. In some cases, however, proximity of the optic nerve and chiasm is a concern. In these cases, intensity-modulated stereotactic radiosurgery (IMRS) can be used to limit the dose to these structures. IMRS planning can be labor intensive, which poses a problem when it is performed on the day of treatment. We describe our methods and results of preprocedure planning for IMRS for patients with lesions in the cavernous sinus or parasellar regions in whom the dose to the optic nerve or chiasm might exceed our acceptable tolerance dose (8 Gy). METHODS Patients whose lesions were more than 4 mm from the optic nerve and chiasm on standard magnetic resonance imaging scans but who were questionable candidates for radiosurgery because of concerns of dose to the optic nerve or chiasm were considered for IMRS. Preprocedure imaging (computed tomography and magnetic resonance imaging) was fused and analyzed using the BrainLAB BrainScan 5.3 treatment planning system. Dynamic conformal arc plans for stereotactic radiosurgery and IMRS were evaluated. Doses to the planning target volume and optic apparatus were assessed by dose-volume histograms and conformality index calculated to characterize the quality of the different plans. When IMRS was used, the preplan allowed for a rapid recalculation on the treatment day, minimizing the time patients were in the head frame before treatment. RESULTS We describe three patients with recurrent pituitary tumors and three with meningiomas. Doses were 1500 to 2000 cGy prescribed to the 80 to 96% isodose line delivered by eight to 22 fields. Tumor volumes ranged from 2.70 to 8.82 cm3 (mean, 5.7 cm3). In five of the six patients, the dynamic conformal arc plan precluded delivery of therapeutic dose without exceeding optic nerve tolerance. On the basis of 95% coverage of target volume, maximum prescription doses of 7.7 to 20.64 Gy were possible with the dynamic conformal arc plans without exceeding 8 Gy to the optic apparatus. IMRS allowed maximum doses of 20 to 31 Gy using the same optic apparatus dose restriction. No complications have occurred, and all tumors have remained stable since treatment (mean follow-up period, 30 mo). CONCLUSION We believe this pretreatment technique streamlines the process for IMRS, allowing for better patient comfort and efficient physician time use.

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36

Smith, Malcolm, Jeffrey Abrams, Edward L. Trimble, and Richard S. Ungerleider. "Dose Intensity of Chemotherapy for Childhood Cancers." Oncologist 1, no. 5 (1996): 293–304. http://dx.doi.org/10.1634/theoncologist.1-5-293.

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37

de Vries, E. G. E., T. C. Hamilton, M. Lind, J. Dauplat, J. P. Neijt, and R. F. Ozols. "Drug resistance, supportive care and dose intensity." Annals of Oncology 4 (1993): S57—S62. http://dx.doi.org/10.1093/annonc/4.suppl_4.s57.

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38

Thigpen, J. T. "Dose-intensity in ovarian carcinoma: hold, enough?" Journal of Clinical Oncology 15, no. 4 (1997): 1291–93. http://dx.doi.org/10.1200/jco.1997.15.4.1291.

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39

Cohen, M. H. "MOPP dose intensity and survival: flawed analysis." Journal of Clinical Oncology 8, no. 4 (1990): 756–57. http://dx.doi.org/10.1200/jco.1990.8.4.756.

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40

Anderson, J. R., and P. F. Coccia. "Is more better? Dose intensity in neuroblastoma." Journal of Clinical Oncology 9, no. 6 (1991): 902–4. http://dx.doi.org/10.1200/jco.1991.9.6.902.

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41

Eijsvogels, Thijs M. H., and Paul D. Thompson. "Exercise Intensity, Dose, and Cardiovascular Disease—Reply." JAMA 315, no. 15 (2016): 1659. http://dx.doi.org/10.1001/jama.2016.0312.

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Alghamdi, Mohammed Abdullah, Richard Lee-Ying, Hao-Wen Sim, et al. "Effect of sorafenib (S) starting dose and dose intensity on survival in patients with hepatocellular carcinoma (HCC): Results from a Canadian multicenter HCC database." Journal of Clinical Oncology 35, no. 15_suppl (2017): 4084. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.4084.

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4084 Background: The SHARP trial showed that S improves survival in advanced HCC. Full dose (FD) S at 400mg bid can be difficult to tolerate, so some clinicians begin with a reduced dose (RD) & escalate as tolerated to maximum dose. The purpose of this study was to determine whether starting dose or dose intensity of S affects survival. Methods: All patients treated with S for HCC from 01/2008 to 06/2016 in British Columbia, Alberta, Ontario (Princess Margaret Cancer Centre & Sunnybrook Odette Cancer Centre), were included. Patient demographics, clinical, tumor characteristics, S starting dose & mean dose intensity were collected & analyzed. Patients were dichotomized into starting FD or RD of S. Mean dose intensity was categorized into > 75%, 50-75% & < 50%. Survival outcomes were assessed with Kaplan-Meier curves & compared with the log-rank test. A Cox-proportional hazard model was constructed with starting dose, dose intensity & relevant clinical & pathologic factors to assess their impact on survival. Results: We included 681 patients. Median age 64 years, 80% men, 37% East Asian, & most frequent causes of liver disease were hepatitis B (33%) & C (29%). ECOG performance status prior to starting S was 0 in 30% & 1 in 60%. Most patients were Childs-Pugh A (86%) at start of S. Overall median survival was 9.1 months (m). S was started at FD in 42% of patients & 31% had a dose intensity > 75%. The median survival for starting FD & RD was 9.4 m & 8.9 m, respectively (p = 0.15). The median survival for a dose intensity > 75% was 9.5 m, 50-75% was 12.9 m & < 50% was 7.1 m (p = 0.005). In multivariate models that adjusted for demographic, stage, performance status, AFP, prior treatment, toxicity & liver function, starting dose (HR 1.1, 95%CI 0.86-1.3, p = 0.51) & dose intensity (50-75% HR 0.93, 95% CI 0.73-1.2; < 50% HR 0.89, 95% CI 0.69-1.1, p = 0.65) were not predictors of survival. Conclusions: Based on our multi-center database, starting HCC patients on a RD of S may be a reasonable since it does not appear to compromise survival. Patients receiving a dose intensity of S at 50-75% appear to have a superior median survival, though this is not significant after controlling for baseline characteristics.

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Stewart, Clinton F. "Pharmacodynamics and Cancer: Practical Aspects of Dose Intensity for Pharmacists." Journal of Pharmacy Practice 4, no. 1 (1991): 11–19. http://dx.doi.org/10.1177/089719009100400103.

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Recent clinical studies have suggested that dose or dose intensity may be a critical factor in achieving an optimal effect from cancer chemotherapy in tumors that are chemosensitive. This article reviews the rationale for the importance of drug dose in cancer chemotherapy and methods of expressing dose intensity. Several clinical studies that provide evidence of the importance of dose intensity are reviewed. The concept of systemic intensity of cancer chemotherapy is discussed. Finally, the practical aspects of dose intensity for the pharmacist are addressed, including dosage calculation, drug preparation and administration, and compliance. The pharmacist plays an integral role in assuring the patient with cancer receive the appropriate dose of cancer chemotherapy.

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Ang, P. T., A. U. Buzdar, T. L. Smith, S. Kau, and G. N. Hortobagyi. "Analysis of dose intensity in doxorubicin-containing adjuvant chemotherapy in stage II and III breast carcinoma." Journal of Clinical Oncology 7, no. 11 (1989): 1677–84. http://dx.doi.org/10.1200/jco.1989.7.11.1677.

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Three hundred thirty-six patients with stage II or stage III breast cancer were treated on an adjuvant protocol containing fluorouracil, doxorubicin, cyclophosphamide, vincristine, and prednisone (FACVP). Depending on the estrogen-receptor (ER) status, the patients were subdivided to receive maintenance chemotherapy with or without tamoxifen. The administered dose intensity of fluorouracil, doxorubicin, and cyclophosphamide (FAC) (mg/m2/wk) relative to the projected dose intensity (based on planned dose) was computed for each patient. The relative dose intensity of the first six cycles of chemotherapy (RDI6) was compared with disease-free survival (DFS). Of the 299 patients who completed at least six cycles of therapy, 83% received dose intensities within 20% of standard intensity (.8 less than or equal to RDI6 less than or equal to 1.2). The group with the highest dose intensity (RDI6 greater than or equal to 1.13) had the longest DFS, though there was not a clear trend of linear association between dose intensity and DFS after adjustment for prognostic factors (P = .16). The patients who received at least standard dose intensity (RDI6 greater than or equal to 1.0) had longer DFS than those whose therapy did not reach standard intensity (RDI6 less than 1.0). This difference was significant in patients with stage III disease (P = .01). The 37 patients who completed fewer than six cycles of chemotherapy had the shortest DFS (5-year DFS of 48% v 65% in the others). This retrospective analysis, in a heterogeneously treated group of patients, did not show the differences in outcome associated with dose intensity as demonstrated in the earlier studies comparing projected dose intensity of various cyclophosphamide, methotrexate-, and fluorouracil (CMF)-containing adjuvant trials. Improved DFS was noted in the stage III patients receiving higher dose intensity. Our failure to demonstrate the differences in stage II patients may be due to the narrow range of dose intensity in this study or to a difference in the dose-response curves depending on the stage of disease.

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Murthy, Vedang, Shirley Lewis, Mayur Sawant, Siji N. Paul, Umesh Mahantshetty, and Shyam Kishore Shrivastava. "Incidental Dose to Pelvic Nodal Regions in Prostate-Only Radiotherapy." Technology in Cancer Research & Treatment 16, no. 2 (2016): 211–17. http://dx.doi.org/10.1177/1533034616661447.

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Objectives: Pelvic lymph nodal regions receive an incidental dose from conformal treatment of the prostate. This study was conducted to investigate the doses received by the different pelvic nodal regions with varying techniques used for prostate radiotherapy. Methods and Materials: Twenty patients of high-risk node-negative prostate cancer treated with intensity-modulated radiotherapy to the prostate alone were studied. Replanning was done for intensity-modulated radiotherapy, 3-dimensional conformal treatment, and 2-dimensional conventional radiotherapy with additional delineation of the pelvic nodal regions, namely, common iliac (upper and lower), presacral, internal iliac, obturator, and external iliac. Dose–volume parameters such as Dmean, D100%, D66%, D33%, V40, and V50 to each of the nodal regions were estimated for all patients. Results: The obturator nodes received the highest dose among all nodal regions. The mean dose received by obturator nodal region was 44, 29, and 22 Gy from 2-dimensional conventional radiotherapy, 3-dimensional conformal treatment, and intensity-modulated radiotherapy, respectively. The mean dose was significantly higher when compared between 2-dimensional conventional radiotherapy and 3-dimensional conformal treatment ( P < .001), 2-dimensional conventional radiotherapy and intensity-modulated radiotherapy ( P < .001), and 3-dimensional conformal treatment and intensity-modulated radiotherapy ( P < .001). The D33% of the obturator region was 64, 39, and 37 Gy from 2-dimensional conventional radiotherapy, 3-dimensional conformal treatment, and intensity-modulated radiotherapy, respectively. The dose received by all other pelvic nodal regions was low and not clinically relevant. Conclusion: The incidental dose received by obturator regions is significant especially with 2-dimensional conventional radiotherapy and 3-dimensional conformal treatment techniques as used in the trials studying elective pelvic nodal irradiation. However, with intensity-modulated radiotherapy, this dose is lower, making elective pelvic irradiation more relevant. Advances in Knowledge: This study highlights that incidental dose received by obturator regions is significant especially with 2-dimensional conventional radiotherapy and 3-dimensional conformal treatment techniques.

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Komuro, Ayumi, Sachiko Seo, Nobuo Mochizuki, Yosuke Minami, and Toshikatu Kawasaki. "Impact of Total Dose Intensity and Relative Dose Intensity (RDI) of R-CHOP on Survival in Patients with DLBCL." Blood 132, Supplement 1 (2018): 4218. http://dx.doi.org/10.1182/blood-2018-99-114227.

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Abstract Background: The standard chemotherapy for diffuse large B-cell lymphoma (DLBCL) is CHOP combined with rituximab (R-CHOP). The guidelines (e.g. NCCN or ESMO) recommend six to eight courses of R-CHOP and the optimal number of courses is still unclear. The relative dose intensity (RDI) was proposed as an indicator for both dose intensity and interval. The previous studies have reported the relation between RDI of CHOP or R-CHOP and treatment outcomes. However, little is known about the low threshold of RDI that affects survival and few studies have compared between RDI and total dose of R-CHOP in the effect on survival. In this study, we evaluated the effect of total dose and RDI of R-CHOP on survival in patients with DLBCL. Patients and methods: We retrospectively analyzed 190 patients with newly diagnosed DLBCL who completed more than 6 courses of R-CHOP between January 2013 and December 2016 at our center. Dose reduction of the CHOP regimen was considered in patients over 70 years of age. RDI was calculated as the ratio of delivered dose intensity (mg/m2/week) to the planned dose intensity (mg/m2/week) and was shown as a percentage. The average of RDI in each drug of R-CHOP was used for the analyses. Risk factors for overall mortality were analyzed using Cox proportional hazards models. Results: Among the 190 patients, median age was 70.0 years (range, 34-91). The numbers of patients were 15, 55, 46, and 66 in low, low-intermediate, high-intermediate, and high risk groups based on the International Prognostic Index (IPI), respectively. Three-year overall survival (OS) was 88%, 100%, and 83% in the patients with 6 (N=64), 7 (N=3), and 8 (N=123) courses of R-CHOP, respectively (p = 0.55). Median RDI was 92% (range, 32 to 117) and the lower quartile of RDI was 72%. Probabilities of OS by the quartile of RDI were shown in Figure 1 and OS was significantly worse in the patients with <72% of RDI than those with ≥72% of RDI (3-year OS, 66% vs 90%; p = 0.001). Subgroup analysis by age (<70 or ≥70 years) showed the similar trend toward worse survival in patients with <72% of RDI in both age groups (<70 years, p=0.001; ≥70 years, p = 0.054). In multivariable analysis, RDI less than 72% (HR, 2.94; 95% CI, 1.25-6.90, p = 0.014) was a significantly important risk factor for mortality, while IPI (HR, 3.2; 95% CI, 0.9-11.4, p = 0.07) or the number of courses of R-CHOP (HR, 1.66; 95% CI, 0.59-4.64, p = 0.34) was not. When analyzing RDI as a continuous variable, RDI (HR, 1.03; 95% CI, 1.01-1.05, p = 0.009) and IPI (HR, 1.49; 95% CI, 1.05-2.12, p = 0.027) were identified as significant risk factors for mortality. Similarly, patients with <72% of RDI had significantly worse progression-free survival (PFS) than those with ≥72% of RDI (Figure 2, 3-year PFS, 59% vs 80%; p = 0.001). However, RDI was not a significantly important risk factor for PFS after adjusting for several factors. Among 190 patients in our cohort, 24 patients died and 17 patients died from recurrence of DLBCL. There is no difference in the number of recurrence between the patients with <72% (N=6) and ≥72% (N=11) of RDI (p = 0.18). Conclusions: Higher RDI of R-CHOP was significantly associated with a higher survival rate in patients with DLBCL, although it did not reach statistical significance in patients over 70 years of age. More than 72% of RDI should be maintained to obtain better OS and PFS. Increase of total dose of R-CHOP was not related to better survival, resulting from the analysis using the number of treatment courses. We conclude that 6 courses of R-CHOP therapy with higher RDI would be recommended for all ages. Further studies are needed to validate our findings. Disclosures Minami: Novartis Pharma K.K.: Consultancy; Takeda Pharmaceutical Company Limited.: Consultancy; ONO PHARMACEUTICAL CO., LTD: Research Funding.

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LeVasseur, N., and S. K. Chia. "Sequential versus concurrent chemotherapy for adjuvant breast cancer: does dose intensity matter?" British Journal of Cancer 117, no. 2 (2017): 157–58. http://dx.doi.org/10.1038/bjc.2017.176.

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Lin, Ruihe, Jie Shan, Taize Yuan, and Chaonan Qian. "Dosimetric comparison of intensity-modulated proton radiotherapy versus intensity-modulated photon-based radiotherapy for breast cancer." Visualized Cancer Medicine 2 (2021): 5. http://dx.doi.org/10.1051/vcm/2021002.

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Purpose: This study aims to compare the dosimetric differences in intensity-modulated proton therapy (IMPT) using pencil beam scanning technology and intensity-modulated photon-based radiotherapy (IMRT) in hypofractionated whole-breast irradiation (HF-WBI) and find out the more beneficial technique. Methods and Materials: Eight breast cancer (BC) patients with pathological stage T1 ~ 2N0M0 were immobilized and underwent 4D-CT scanning used deep inspiration breath-hold (DIBH) technology. The IMPT and IMRT plans were designed for each patient. The IMPT plans used two en-face beam angles. IMRT plans were designed using the field in field technique. The optimization constraints of the two types of plans were identical. Prescription dose and regimen was 40.05 Gy (relative biological effect [RBE])/15 fx with a 10 Gy (RBE)/5 fx boost, five fractions a week. A dose of 95% of the target volume should not be less than the prescribed dose. The target coverage was evaluated using D1, D2, D50, D95, D98, and D99. The target dose distribution and conformity were evaluated using the Conformity index (CI) and the homogeneity index (HI). The Organs at risk (OARs) were evaluated using mean dose (Dmean) and maximum dose (Dmax). Ipsilateral Lung and Contralateral Lung were evaluated additionally using V5, V10, V20, V30. Results: The mean dose (Dmean) of the Heart (P = 0.012), Ipsilateral Lung (P = 0.036), Contralateral Lung (P = 0.012), and Spinal Cord (P = 0.012) were significantly reduced in IMPT plans. The IMPT also showed a tendency to reduce the V20 (P = 0.05) and V30 (P = 0.05) of the Ipsilateral Lung. But there was no significant difference in target coverage, homogeneity, and conformity between the IMRT and IMPT plans. Conclusion: Compared to IMRT, the IMPT using pencil beam scanning technology can spare OARs without compromising target coverage in BC patients undergoing HF-WBI, which potentially reduce the incidence of radiation-related adverse effects and thus may positively impact long-term survival.

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Lewis, Ian J., Simon Weeden, David Machin, Dan Stark, and Alan W. Craft. "Received Dose and Dose-Intensity of Chemotherapy and Outcome in Nonmetastatic Extremity Osteosarcoma." Journal of Clinical Oncology 18, no. 24 (2000): 4028–37. http://dx.doi.org/10.1200/jco.2000.18.24.4028.

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PURPOSE: To examine the relationship between received dose, received dose-intensity (RDI), and survival in patients with osteosarcoma. PATIENTS AND METHODS: Between 1983 and 1993, the European Osteosarcoma Intergroup (EOI) conducted two randomized trials involving patients with high-grade, nonmetastatic, biopsy-proven osteosarcoma of the extremity. These trials shared a common treatment arm of doxorubicin (DOX) 75 mg/m2 and cisplatin (CDDP) 100 mg/m2 planned for six cycles at 3-week intervals. Definitive surgery was scheduled at week 9, after three cycles. Survival time was calculated from 122 days, the scheduled end of chemotherapy. RESULTS: A total of 287 patients randomized to DOX/CDDP received at least one cycle of chemotherapy, and 232 (81%) received all six cycles. On average, 79% of the intended dose of DOX and 80% of the intended dose of CDDP was given. Mean time to completion of chemotherapy was 1.27 times that specified by the protocol. Mean RDI was 0.64 for DOX (SD = 0.19) and 0.65 for CDDP (SD = 0.18). Progression-free survival was lower for those who received one to five cycles compared with those who completed all six cycles (hazards ratio, 1.69; 95% confidence interval, 1.03 to 2.78). Survival and progression-free survival were lowest for patients with RDI less than 0.6, although these differences were not statistically significant at the 5% level. There was no clear evidence of preoperative dose or dose-intensity influencing histologic response. CONCLUSION: This analysis did not establish a clear survival benefit for increasing received dose or dose-intensity in the context of this two-drug regimen. The hypothesis that increasing dose-intensity may improve survival in osteosarcoma requires prospective evaluation.

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Meyer, R. M., G. P. Browman, M. L. Samosh, et al. "Randomized phase II comparison of standard CHOP with weekly CHOP in elderly patients with non-Hodgkin's lymphoma." Journal of Clinical Oncology 13, no. 9 (1995): 2386–93. http://dx.doi.org/10.1200/jco.1995.13.9.2386.

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PURPOSE To determine whether modifying the standard regimen of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) from full doses given every 3 weeks to one-third doses given weekly (chop) increases the received chemotherapy dose-intensity in elderly patients with advanced-stage intermediate-grade lymphoma. PATIENTS AND METHODS Consenting patients, age > or = 65 years who had acceptable cardiac, renal, and liver function and an Eastern Cooperative Oncology Group (ECOG) performance status less than 4, were stratified by bone marrow and performance status and randomized to receive standard CHOP or weekly chop. Drug doses were attenuated or escalated according to a defined dose-modification schedule. The primary outcome was average relative received dose-intensity. Secondary outcomes included response, progression-free and overall survival, toxicity, and performance status. RESULTS Nineteen patients were allocated to each group. No difference in received dose-intensity was seen. When dose-intensity was calculated for the first six cycles of therapy, average relative received dose-intensity was .92 with CHOP versus .89 with weekly chop (P = .5); when calculated for the first 18 weeks of therapy, values were .88 with CHOP versus .89 with weekly chop (P = .8). The complete response rate was 68% with CHOP versus 74% with weekly chop (P = .9). At 2 years, the progression-free survival rate was 57% with CHOP versus 46% with weekly chop (P = .16) and the survival rate was 74% with CHOP versus 51% with weekly chop (p = .05). More myelotoxicity was seen with CHOP. CONCLUSION We conclude that CHOP can be given in sufficient doses to elderly patients and that weekly chop does not increase received dose-intensity. Progression-free and overall survival are unlikely to be superior with weekly chop, and may be worse. CHOP should remain the standard against which new therapies for elderly patients with intermediate-grade lymphoma are compared.

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