Journal articles on the topic 'Imago relationship therapy (IRT)'

Marriage and family common factors are used to understand the curative elements in marriage and family therapy (MFT) models of treatment. Sprenkle, Davis, and Blow identified four common factors of well-established MFT treatment models. This article deconstructs Imago relationship therapy (IRT), a widely used model of couples therapy, for the purpose of determining whether IRT utilizes the four curative common factors of MFT in its theory and practice. The analysis indicates that IRT does utilize the four broad common factors of MFT shared by other well-established models of MFT in addition to its narrow model factors that make it unique.

Empathy is directly related to one’s satisfaction with a romantic partner, and therefore, most approaches to couples therapy explicitly address empathy as a means for creating positive relational change. Imago relationship therapy (IRT) is practiced extensively worldwide yet lacks research validating its effectiveness. Given IRT’s focus on developing empathy within the members of the romantic partnership, it is important to examine how empathy contributes to change in relationship satisfaction. This random and controlled study examined the impact of 12 weeks of IRT treatment on individual ( N = 60) empathy levels. Results showed a significant interaction between time and condition and found significant increases in treatment group empathy levels at each of three assessment points. These findings begin to emphasize the impact of IRT on couple empathy levels and highlight the potential benefits of using this particular therapeutic modality to promote positive relational change within romantic relationships. The research would have benefited from greater diversity within the sample and a greater understanding of the specific therapist interventions that impact client couple empathy levels.

289 Background: This clinical study assessed the potential of helical tomotherapy-based, image-guided radiotherapy (IGRT) to increase the accuracy of bladder irradiation using a plan of the day adaptive radiotherapy (ART) technique. Methods: Ten patients with stage T2b-T4- N0 M0, histologically proven bladder transitional cell carcinoma, who underwent bladder preservation with trimodality therapy in an ongoing trial, are reported. All patients received a dose of 64Gy/32# to the whole bladder. Seven of these also received a simultaneous integrated boost of 68Gy/32 fractions to tumor bed. The ART technique entailed the generation of six planning PTVs and thus six separate IMRT plans for each patient. All patients underwent daily pre and post treatment MVCT imaging to correct for positioning errors, choose the plan of the day, depending on deformation of the bladder, and verify intrafraction filling at the end of treatment. Margins needed to encompass the bladder wall in each direction during radiotherapy was determined in the following three scenarios: (a) centers with availability of daily IGRT and performing ART, (b) centers with IGRT not doing ART, and (c) centers without IGRT using electronic portal imaging for setup. Results: At a median follow-up of 12.2 months, all patients had a complete response in the bladder and one patient had a pelvic nodal recurrence. No patient developed treatment related grade 3 toxicity. Post treatment MVCT scans (n=315) were used to generate margins for centers with varying resources. Overall, the margin needed to encompass the anterior and superior walls 85 to 95% of the time was more than the other walls (Table, margins for six walls in cm). Maximum geographical miss in spite of IGRT was noted for the superior (13.8%) and anterior walls (10.3%). Conclusions: Plan of the day ART is a feasible and promising technique for optimal treatment and dose escalation in bladder cancer. [Table: see text] No significant financial relationships to disclose.

4131 Background: The purpose of this study is to determine the effect of image-guided radiotherapy on survival in adenocarcinoma of the biliary tract. Methods: Between 1995 and 2005, 43 pts with primary biliary tract (gallbladder or bile duct) neoplasms were treated with radiotherapy. 26 of the pts were female and 17 were male. Their average age at registration was 64, and ranged from 25 to 86. Twenty-five pts (58%) were Hispanic, while 18 (42%) were white. 31 pts (72%) underwent surgical treatment, most having cholecystecomy (50%). 29 pts (67%) had chemotherapy: 21 (72%) were given fluorouracil-based drugs, 2 (7%) received gemcitabine, and 6 (21%) received other agents. 23 pts (53%) received conventional radiation treatment using AP/PA, AP/PA with opposing lateral, or AP with opposing lateral fields. 20 pts (47%) received IG-IMRT using Nomos Peacock and daily ultrasound image guidance (BAT, Nomos, Cranberry, PA). For daily ultrasound-based image-guidance, sagittal and axial ultrasound images were acquired, and used to align pt anatomy through superimposition of CT derived organ and vascular guidance structures. Pts were treated using a boost technique to a reduced volume at gross disease after an initial dose to gross tumor and clinically evident microscopic disease. Results: Median dose to target was 54 Gy, with median conventional and IG-IMRT total doses of 48.6 and 60 Gy respectively (p=0.05). Treatment was well tolerated, with only two patients reporting RTOG grade 3 toxicity. All other patients exhibited Grade ≤2, with 23/43 reporting Grade ≤1 The median survival time from the date of registration for all patients was 8.7 months; conventional RT pts had a median survival of 6.1 months, while the IG-IMRT cohort had a median survival of 11.4 months (p = .02). Conclusions: Ultrasound-based image-guided IMRT is a feasible mechanism of delivering moderate dose escalation in conjunction with tighter safety margins, resulting in acceptable acute toxicities. Early survival data with this novel technique are encouraging and demonstrate a notable survival differential using image guided radiotherapy as component of multi-modaility regimens. No significant financial relationships to disclose.

This paper compares the approaches to Sharon’s case presented in two articles that appear earlier in this module, my paper (Westerman, 2021a), which was based on Interpersonal Defense Theory, and the paper by Critchfield, Dobner-Pereira, and Stucker (2021a), which was based on Interpersonal Reconstructive Therapy (IRT). I begin by considering differences in general between the ways in which these two perspectives approach case formulation. I then turn to comparing the formulations of Sharon’s case based on the two perspectives. Among other things, this part of the paper contrasts IRT’s focus on copy processes and the Gift of Love with Interpersonal Defense Theory’s focus on functionalist processes that involve the temporal organization of the parts of noncoordinating defensive interpersonal patterns. The second half of the paper compares the treatment implications of the two approaches in general terms and as they relate to Sharon’s case in particular. Implications for treatment are discussed regarding both insight-oriented interventions and enacted interventions at the level of therapy relationship processes.

4622 Background: To evaluate the benefits of adjuvant intra-operative radiation therapy after curative resection in advanced pancreatic cancer (APC) patients, a multi-center phase III trial was conducted by 11 participating institutions in Japan. Methods: Eligibility included pts with potentially resectable APC (duct cell origin) by image diagnosis. Patients were randomized in a 1:1 ratio to adjuvant IORT or surgery alone less than a week before surgery. Stratification factors were tumor size (TS1/TS2,3,4), location (head/body and tail), and institution. Patients who were assigned to adjuvant IORT arm received IORT after curative resection before reconstruction. IORT consisted of 25Gy with electron beam energies of more than 6MeV and was delivered by the round shaped acrylic cylinder of 6–8cm diameter. The radiation field included the tumor bed and in most cases included the celiac axis, superior mesenteric artery, and the portal vein. The primary endpoint was overall survival. The secondary endpoint was local control rate at 2 years after surgery. Assuming 65 eligible pts in each arm, the study had 0,8 power to detect 20% difference in 2-year survival rate. Results: Between 05/2002 to 12/2006 198 pts were randomized and 153 pts underwent curative resection with assigned treatment. Among the 153 pts with curative resection, seven pts revealed ineligible by the histological examination. Finally full analysis sets were 144 pts. Seventy three pts were in the IORT arm and 71 pts in the surgery alone arm. There was only one hospital death in the IORT arm. Cause of the death was intraabdominal arterial bleeding due to pancreatic fistula. Conclusions: We now are collecting the final follow up data. The final analyses will be presented at the meeting. No significant financial relationships to disclose.

71 Background: The purpose of this study was to compare clinical outcomes in a cohort of intermediate- and high-risk prostate cancer patients treated with either dose-escalated adaptive IGRT or pelvic external beam RT with high-dose rate brachytherapy boost (EBRT+HDR). Methods: 1,520 patients with clinical stage T1-T3 N0 M0 prostate cancer were treated with either CT-based offline adaptive IGRT (n=1,037) or EBRT+HDR, n=438) at William Beaumont Hospital. For IGRT, the CTV included the prostate and proximal seminal vesicles only. Median dose (minimum to cl-PTV) delivered via 3D conformal RT or intensity-modulated RT was 75.6 Gy (range: 73.8-79.2 Gy). For EBRT+HDR, the whole pelvis was treated to 46 Gy + 2 HDR implants with a median of 10.5 Gy (8.75-11.5 Gy) per implant. 208 patients from each group were matched based on criteria of pretreatment PSA ± 4 ng/mL, same Gleason score, T stage ± 2 sublevels, and use of neoadjuvant androgen deprivation therapy (ADT). Results: Mean follow-up was 5.1 years for IGRT vs 7.0 years for EBRT+HDR. Mean pretreatment PSA was 9 for both groups. Mean Gleason was 7 for both groups. EBRT+HDR patients were younger (67 vs 71 years, p<0.01) with a higher percentage of positive biopsy cores (51% vs 39%, p<0.01). Intermediate risk patients comprised 78% and 76% for IGRT and EBRT+HDR, respectively (p=0.56). 42% in each treatment group received neoadjuvant or concurrent ADT. 5-year biochemical control (BC) based on the Phoenix definition was 91% for IGRT vs 87% for EBRT+HDR (p=0.60). For intermediate-risk, 5-year BC was 94% vs 87% (p=0.71) and was 86% vs 86% (p=0.83) for high-risk patients. No significant differences were noted between the 2 groups for local recurrence, distant metastasis, clinical failure, overall survival, and cause-specific survival. Conclusions: In this matched-pair analysis of 416 patients, treatment of intermediate and high-risk prostate cancer with either offline adaptive IGRT or EBRT+HDR yielded excellent clinical outcomes without significant differences. The omission of pelvic radiotherapy in the IGRT patients did not appear to be associated with poorer clinical outcomes with modern high-dose RT. No significant financial relationships to disclose.

302 Background: Our institution has reported a strategy of using neoadjuvant GTX (gemcitabine, docetaxel, and capecitabine) chemotherapy followed by 5FU-based intensity-modulated radiation therapy (IMRT) for borderline resectable pancreas cancer. We now report our early experience with induction chemotherapy followed by stereotactic body radiation therapy (SBRT). Methods: This retrospective review evaluates our initial 5 fraction SBRT experience in 15 patients following induction chemotherapy for borderline resectable pancreatic cancer. Staging included pancreatic protocol CT, endoscopic ultrasound, and PET/CT scan. Induction regimens consisted of GTX for 3 cycles in 12 patients and gemcitabine alone in 3. Daily SBRT was delivered to the pancreas at least 1 week after completing systemic chemotherapy. Endoscopically implanted fiducial markers and daily cone beam CT were used for image guidance. Treatment was delivered on a Varian Trilogy unit using 6-15 MV photons. Doses were selected based on dose painting the portion of tumor adjacent to the vasculature to a higher dose while meeting normal tissue constraints. The entire gross tumor received a dose of 5-6 Gy per fraction while the portion of the tumor adjacent to the vasculature resulting in the borderline designation received up to 8 Gy per fraction. Patients were re-imaged 3-4 weeks after SBRT for consideration of surgery. Results: There were no acute or late grade 3 toxicities. At the time of this analysis, not all treated patients have reached the restaging time point, but 9 of 15 (60%) were candidates for resection. Six patients have gone to resection with negative margins and without any increased complications. Two patients were found to have disease surrounding the vasculature preventing resection. One patient had cardiac issues at surgery and resection was aborted. One patient was explored and found to have liver metastases. Conclusions: Integration of SBRT in conjunction with systemic therapy is well-tolerated and appears to facilitate margin-negative resection in borderline resectable pancreatic cancer. No significant financial relationships to disclose.

Abstract Background: Solid tumor patients are at a heightened risk for developing therapy-related myeloid neoplasms (tMN). Recent studies show evidence of somatic mutations in leukemia-associated genes in normal healthy individuals, referred to as clonal hematopoiesis (CH). We and others have shown that clonal hematopoiesis (CH) is also frequent in cancer patients. A detailed characterization of the relationship between exposure to specific oncologic regimens, the molecular features of CH presentation and how these relate to tMN risk is warranted to inform treatment decisions, early detection and prevention strategies. Methods: To determine the relationship between CH and oncologic therapy, we performed a systematic interrogation of CH in a cohort of 17,478 solid tumor patients with clinical, outcome and molecular profiling by MSK-IMPACT. MSK-IMPACT is a targeted panel of cancer-associated mutations used to screen tumor samples against a blood control sample. Mutation detection was performed on blood derived sequencing data (median coverage at 600x) using the matched tumor as a comparator and accounted for background sequencing error rates. Results: Overall, 40% of the 17,478 patients were treatment naïve prior to IMPACT testing, 37% had received chemotherapy alone, 17% had received radiation therapy and 18% had received both. CH was identified in 4013 (23%) of patients, median VAF was 4% (range=1-80%). The vast majority (76%) had a single mutation whereas 9% had two and 5% had three or more. The number of mutations correlated with clone size (p-value=<0.001). The proportion of patients with CH greatly increased with each decade of life (p<0.001). In multivariate regression analyses adjusted by age, CH was more often found in former or current smokers (p=0.03) than in non-smokers and in Whites compared to Asians (p=0.005) and Hispanics (p=0.005). There were no significant differences by gender. Rates of CH varied greatly by solid tumor type but when limited to treatment naïve patients, no significant differences remained, suggesting that this was driven by different treatment exposures. As previously reported in healthy patient cohorts, CH in the DNA hydroxymethylation pathway predominated (52% of total CH mutations). There was a higher proportion of patients with mutations in the DNA repair/cell cycle pathway (including TP53, PPM1D and CHEK2) and among patients who received chemotherapy and radiation therapy prior to IMPACT testing compared to those who were treatment naïve (p<0.001). Exposure to prior cytotoxic chemotherapy (OR=1.2, 95%CI=1.0-1.3; p=0.03) and radiation therapy (OR=1.6, 95%CI=1.4-1.9, p<0.002) was associated with having CH while exposure to immunotherapy and targeted therapy was not. There was evidence of specific gene, treatment and dosage effects. To further examine the relationship between oncologic therapy and clonal evolution of CH mutations, we have collected 375 sequential samples collected at least 18 months apart. A subset of patients with CH were consented to germline testing for cancer predisposition genes (N=1835). We observe a lower rate of CH among patients with a germline mutation in the homologous recombination deficiency pathway (ie BRCA1, BRCA2) (OR=0.66, 95% CI: 0.43-0.99, p-value=0.05) and a higher rate of CH among patients with a germline mutation in the cell cycle/DNA repair pathway (i.e. CHEK2, TP53) when compared to patients without germline mutations (OR=1.6, 95% CI: 1.0-2.6, p-value=0.05). In analyses stratified by prior treatment, patients with germline mutations in the cell cycle/DNA repair pathway (i.e. CHEK2, TP53) with prior radiation therapy exposure were more likely to have CH compared to patients with no germline mutations who were exposed to radiation therapy (OR=4.1,95%CI=1.1-17.0, p-value for interaction=0.04). Conclusions: CH is frequent in solid tumor patients and can be reliably detected when a matched tumor normal targeted gene sequencing approach is performed. Beyond age, CH is strongly associated with race, smoking and importantly prior exposure to oncologic therapy with evidence of specific treatment effects. Taken together, we show that screening of CH in cancer cohorts is critical to the development of future clinical guidelines, the development of risk-adapted treatment decisions, surveillance programs and definition of patient subsets at highest risk for tMN. Disclosures Coombs: Incyte: Other: Travel fees; DAVA Oncology: Honoraria; Abbvie: Consultancy; H3 Biomedicine: Honoraria; AROG: Other: Travel fees. Tallman:Daiichi-Sankyo: Other: Advisory board; Cellerant: Research Funding; BioSight: Other: Advisory board; AROG: Research Funding; Orsenix: Other: Advisory board; AbbVie: Research Funding; ADC Therapeutics: Research Funding. Yabe:Y-mAbs Therapeutics: Consultancy. Levine:Celgene: Consultancy, Research Funding; Novartis: Consultancy; Gilead: Honoraria; Isoplexis: Equity Ownership; Epizyme: Patents & Royalties; Prelude: Research Funding; C4 Therapeutics: Equity Ownership; Janssen: Consultancy, Honoraria; Imago: Equity Ownership; Qiagen: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Research Funding; Loxo: Consultancy, Equity Ownership.

Clonal hematopoiesis (CH), defined by expansion of clones in the hematopoietic system, has been linked to internal (aging) and external (smoking and oncologic therapy) factors in patients with advanced solid tumors. The effects of inherited variants, however, have yielded inconclusive results in few studies so far. While comparison of CH prevalence between monozygotic and dizygotic pairs failed to detect genetic predisposition to CH, others have shown associations with germline variants near TERT and TET2, and a potential link between pathogenic CHEK2 germline variants and CH has been proposed. Here, utilizing prospective tumor-blood paired sequencing data from a large institutional clinical cohort, we link inherited pathogenic variants in cancer predisposition genes to CH and show interactions between germline and somatic mutations in DNA damage repair (DDR) genes. We analyzed sequencing data from 32,748 cancer patients who have undergone MSK-IMPACT testing using paired tumor and blood samples to study the associations between CH and rare pathogenic and likely-pathogenic (P/LP) germline variants. P/LP germline mutations were identified in the blood using an in-house developed random forest algorithm, trained using known P/LP mutations. Following joint anonymization of P/LP germline mutations and CH variants, linear regression models by gene were used to test for associations, accounting for known CH confounders. In our cohort, 9,697 patients (29.6%) harbored at least one CH mutation, while P/LP germline variants were detected in 1,793 of these CH patients. P/LP germline variants in CHEK2 (OR=1.29, p=4.49x10-2) were found to be significantly associated with CH in a pan-cancer analysis. Interestingly, germline P/LP and CH co-mutations in CHEK2 were very rare; we identified only one patient with CH and germline mutations in CHEK2 out of 161 patients with germline CHEK2 mutations, compared to 304 patients with CH CHEK2 mutation when CHEK2 is wild-type in the germline. In contrast, ATM and TP53 showed increased number of patients with co-mutations in P/LP germline and CH mutations in the same gene, with 14 out of 84 patients with germline mutations in ATM compared to 254 when not mutated (OR=7.05, p=2.08x10-7) , and 3 out of 16 compared to 387 for TP53 (OR=10.94, p=5.44x10-3). Further, we found mutual exclusivity between CHEK2 P/LP germline variants and CH mutations in PPM1D (OR=0.18, p=1.79x10-2). This relationship was replicated by comparing CHEK2 germline mutations and somatic PPM1D mutations in the solid tumor samples within the same cohort and same pattern of mutual exclusivity also persisted in comparisons of other DDR pathway genes (i.e. ATM vs PPM1D and TP53 vs PPM1D). When studying specific cancer types, a significant association between CHEK2 P/LP germline variants and CH in breast cancer patients was also identified (OR=2.33, p=2.64x10-3). Furthermore, trends between germline mutations in ATM and CH rates in breast cancer (OR=1.84, p=9.82x10-2) and lung adenocarcinoma (OR=2.22, p=8.91x10-2) patients were observed. Our results support the already reported link between rare pathogenic germline mutations in CHEK2 with CH in cancer patients, with stronger association among breast cancer patients (Comen E. et al, 2019). Moreover, this study suggests a close relationship between inherited variants and CH mutations within the DDR genes in solid tumor patients and points out to interesting mutual exclusivity patterns between these same genes. Intriguingly, hematopoietic stem cells have been largely related to proficient DDR systems in order to regulate HSC maintenance and tissue homeostasis in the hematopoietic system. All in all, associations identified in this study might translate into enhanced clinical surveillance for CH and associated comorbidities cancer patients harboring these germline mutations. Disclosures Bolton: GRAIL: Research Funding. Papaemmanuil:Novartis: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Illumina: Consultancy, Honoraria; Prime Oncology: Consultancy, Honoraria; Isabl: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; Kyowa Hakko Kirin: Consultancy, Honoraria; MSKCC: Patents & Royalties. Levine:Prelude Therapeutics: Research Funding; Qiagen: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy; Astellas: Consultancy; Morphosys: Consultancy; Novartis: Consultancy; Amgen: Honoraria; Gilead: Honoraria; Roche: Consultancy, Honoraria, Research Funding; Lilly: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; C4 Therapeutics: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; Loxo: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; Isoplexis: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; Imago: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees. Berger:Illumina: Research Funding; Grail: Research Funding; Roche: Consultancy. Zehir:Illumina: Honoraria; Memorial Sloan Kettering Cancer Center: Current Employment.

Background: Although ~60% of patients with DLBCL are cured with frontline therapy, outcomes for those with relapsed/refractory disease remain poor. Tumour cells exploit immune checkpoint pathways, including the PD1/PDL1 axis, to evade and inhibit host anti-tumour immune responses. PD1/PDL1 expression and cytogenetic 9p24 alterations in some DLBCL subtypes provide additional rationale for PDL1 inhibition (PD-L1i) in DLBCL. Though single agent PD1i yields a disappointing ORR of 10-30% in heavily pre-treated DLBCL, some responses are durable.1 Radiotherapy (RT) is an established mechanism of stimulating anti-tumour immunity via increased circulating tumour antigen, immunogenic cell death and T-cell recruitment and activation in the tumour microenvironment. Synergy between concomitant immune checkpoint inhibition (ICI) and RT has been demonstrated in preclinical studies2 and solid tumours; a recent study in non-small cell lung cancer demonstrated an ORR of 36% with pembrolizumab + RT compared with 18% with pembrolizumab alone.3 RT hypofractionation appears critical to the abscopal effect when used with ICI,4 and concurrent RT and PD-L1i is more successful than sequential treatment.5 RT to multiple sites may broaden the spectrum of tumour antigen released and overcome clonal variation between disease sites; a dose-response relationship between RT and antigen release has yet to be established. This phase I study aims to determine the safety profile of escalating dose and number of sites of RT in combination with Durvalumab (MEDI4736), an anti-PD-L1 monoclonal antibody, in relapsed/refractory DLBCL, including primary refractory DLBCL and transformed follicular lymphoma. Study Design and Methods: RaDD (NCT03610061) includes eligible pts who have received ≥1 prior line of therapy and are ineligible for or relapsed after autologous stem cell transplantation (SCT). Pts with active autoimmune disease, CNS involvement, prior allogeneic SCT or chronic steroid use are excluded. Treatment comprises external beam RT to target site(s) daily for 5 days (Fig 1). Durvalumab 1500mg IV commences on day 2 of RT and continues 4-weekly until disease progression. Pts can continue until a second radiological progression if clinical benefit is ongoing. The primary endpoint is the toxicity, drug pharmacokinetics, maximum tolerated dose (MTD) and recommended phase two dose (RP2D) of simultaneous RT plus durvalumab. Secondary endpoints are response rates; progression free survival; and overall survival. An exploratory PET substudy will employ novel tracers to characterise the local and systemic immune response via assessment of the biodistribution of durvalumab (with 89Zr-Durvalumab) and CD8+ T cells (with 89Zr -Df-IAB22M2C). Biomarker sample collection is synchronised with PET response assessment. A comprehensive translational substudy will apply high throughput technologies to tissue and sequential blood samples to characterise the tumour-immune system interaction and correlate novel host, tumour and tumour microenvironment factors with treatment responses and toxicity. Findings may inform the RP2D. RT dose and site escalation will proceed according to a 3+3 design with 5 dose levels (cohorts 1-5, Fig 2). The dose limiting toxicity assessment window is the first 28 days. Projected enrolment for determination of MTD and RP2D is 6-30 pts pending toxicity. Recruitment will continue to a total of 36 pts to allow for secondary endpoint analysis. 5 pts have been enrolled to date. Acknowledgements: Victorian Cancer Agency (funding), Astra Zeneca (durvalumab and funding), Celgene (funding), Imaginab (89Zr -Df-IAB22M2C) References: 1. Ansell SM et al. Nivolumab for Relapsed/Refractory Diffuse Large B-Cell Lymphoma in Patients Ineligible for or Having Failed Autologous Transplantation. J Clin Oncol. 2. Deng L et al. Irradiation and anti-PD-L1 treatment synergistically promote antitumor immunity in mice. J Clin Invest. 3. Theelen W et al. Effect of Pembrolizumab After Stereotactic Body Radiotherapy vs Pembrolizumab Alone on Tumor Response in Patients With Advanced Non-Small Cell Lung Cancer. JAMA oncology. 4. Golden EB et al. An abscopal response to radiation and ipilimumab in a patient with metastatic non-small cell lung cancer. Cancer Immunol Res. 5. Sharabi AB et al. Radiation and checkpoint blockade immunotherapy: radiosensitisation and potential mechanisms of synergy. Lancet Oncology. Disclosures Hawkes: Janssen-Cilag: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck Sharp & Dohme: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Research Funding, Speakers Bureau; Roche: Research Funding; Takeda: Speakers Bureau; Astra Zeneca: Research Funding; Merck KgA: Research Funding; Mundi pharma: Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche/Genentech: Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses, Speakers Bureau. Manos:Janssen: Honoraria; Novo Nordisk Pharmaceuticals: Other: Travel. Chong:Merck Serono: Research Funding; Hutchison Medipharma: Research Funding; Pharmacyclics: Research Funding; Novartis: Research Funding; Bayer: Research Funding; BMS: Research Funding. MacManus:National Health and Medical Research Council Australia: Research Funding. Keane:MSD: Consultancy; Celgene: Consultancy; Gilead: Consultancy; BMS: Research Funding; Roche: Consultancy, Other: Travel Grant. Scott:Cancer Council Victoria: Research Funding; Cancer Australia: Research Funding; Avipep: Consultancy; IBA: Consultancy; Paracrine Therapeutics: Equity Ownership, Patents & Royalties; Life Science Pharmaceuticals: Equity Ownership; NHMRC: Research Funding; Abbvie: Consultancy, Patents & Royalties; Cure Brain Cancer: Research Funding; Medimmune: Consultancy; Humanigen: Patents & Royalties. Shortt:Celgene: Consultancy, Speakers Bureau; BMS: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Astex: Research Funding; Amgen: Research Funding; Gilead: Speakers Bureau; Takeda: Speakers Bureau. Ritchie:Amgen: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy; BMS: Research Funding; Takeda: Research Funding; Beigene: Research Funding; Imago: Research Funding; Novartis: Honoraria; Sanofi: Honoraria. Lee:Australian Nuclear Science and Technology Organisation: Membership on an entity's Board of Directors or advisory committees. Koldej:NanoString Technologies: Other: Travel grant. OffLabel Disclosure: Durvalumab is an anti-PD-L1 monoclonal antibody.

Background Stably acquired mutations in hematopoietic cells represent substrates of selection that may lead to clonal hematopoiesis (CH), a common state in cancer patients that is associated with a heightened risk of leukemia development. Owing to technical and sample size limitations most CH studies have characterized gene mutations or mosaic chromosomal alterations (mCAs) individually. The relationship between acquired gene mutations and mCAs in CH and their joint roles in leukemia development have not been systematically investigated. Methods We developed a method to reliably map mCAs at low cell fractions from deep targeted sequencing data. We applied this method in a cohort of 32,442 solid tumor patients who have undergone prospective clinical sequencing (MSK-IMPACT). We characterized gene mutations in our patient cohort using an established variant calling procedure from our previous studies. Results We jointly characterized 383 mCA events (median aberrant cell fraction 32%, range 10%-90%) and 14,789 mutations across 457 genes. mCA was significantly associated with age (OR=1.8, P&lt;0.001), male gender (OR=1.4, P=0.012), white race (OR=1.5, P=0.033) and prior receipt of external beam radiation therapy (OR=1.7, P=0.022). 217 (63%) mCAs co-occurred with at least one gene mutation, while 129 (37%) did not (OR=3.9, P&lt;0.001). mCA was especially enriched in CH cases with high mutation number and VAF, detectable in 5.8% of subjects with ≥3 gene mutations and 4.8% of those with mutations at &gt;20% VAF, compared to 1% of the general cohort. We identify co-mutational patterns characteristic of diverse mechanisms of clonal selection. We observe that mutations in DNMT3A, TET2, JAK2, MPL, EZH2, TP53 and ATM form recurrent double-hits with deletions or CNLOHs, resulting in either oncogene mutant dosage adjustment or inactivation of tumor suppressors. Notably, certain mCA events were highly directed events acting on previously acquired gene mutations in the corresponding loci. Of six events of 7qCNLOH, all six co-localized with an EZH2 (7q36.1) mutation (q&lt;0.001). Of 12 cases with 9pCNLOH, 11 (92%, q &lt;0.001) co-localized with a JAK2 V617F mutation. 4 out of 9 (44%, q &lt;0.001) 1pCNLOH events co-localized with a MPL (1p34.2) mutation. In addition, we observe recurrent composite genotypes (4q24-/SRSF2, 7qCNLOH/ASXL1, 20q-/U2AF1) indicative of co-operating or epistatic interactions as well as loss of gatekeeper function (i.e. TP53) presenting with multiple chromosomal aneuploidies (5-, 7-, 3+). In total, these recurrent composite genotypes resembling known genetic interactions in leukemia genomes underlie 23% of all detected autosomal mCAs. During patient follow-up, the 3-year cumulative incidence of leukemias was significantly higher in patients with composite CH genotypes (14.6%, CI: 7-22%) as compared to patients with either mCA, gene mutation alone or no CH, of which all had a 3-year cumulative incidence of &lt;1% (Figure 1). We performed a multivariable cause-specific Cox regression model and showed that mCA was independently predictive of subsequent leukemia diagnosis (HR=14, 95% CI: 6-33, P=1.2e-09) after adjusting for number of gene mutations and VAF in putative drivers. Conclusions Our joint characterization of gene mutations and mCAs in a large prospective sequencing cohort reveals a previously unrecognized layer of complexity in the evolutionary dynamics of clonal hematopoiesis that converges towards characteristic genotypes associated with distinct leukemia subtypes. This puts mCAs in the context of the continuous evolutionary process of oncogenesis that can often span years and sheds new lights on its patterns of acquisition and progression. We demonstrate that the integration of chromosomal aberrations provides additional resolution to risk stratification as well as interpretation of clinical phenotypes and that mCAs should be screened in conjunction with gene mutations to improve existing CH surveillance programs in cancer patients. Disclosures Bolton: GRAIL: Research Funding. Medina:Isabl: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees. Mantha:MJH Associates: Honoraria; Physicians Education Resource: Honoraria. Solit:Pfizer: Honoraria; Loxo Oncology: Honoraria; Lilly Oncology: Honoraria; Illumina: Honoraria; Vivideon Therapeutics: Honoraria. Diaz:Neophore: Consultancy, Current equity holder in private company; Merck: Consultancy; Johns Hopkins University: Patents & Royalties; Jounce Therapeutics: Current equity holder in private company; Thrive Earlier Detection: Current equity holder in private company; Personal Genome Diagnostics: Consultancy, Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees. Berger:Illumina: Research Funding; Roche: Consultancy; Grail: Research Funding. Levine:Lilly: Consultancy, Honoraria; Janssen: Consultancy; Roche: Consultancy, Honoraria, Research Funding; Loxo: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; Imago: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; C4 Therapeutics: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; Isoplexis: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Research Funding; Prelude Therapeutics: Research Funding; Gilead: Honoraria; Amgen: Honoraria; Morphosys: Consultancy; Novartis: Consultancy; Astellas: Consultancy; Qiagen: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees. Zehir:Memorial Sloan Kettering Cancer Center: Current Employment; Illumina: Honoraria. Papaemmanuil:Celgene: Consultancy, Honoraria, Research Funding; Prime Oncology: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Illumina: Consultancy, Honoraria; Kyowa Hakko Kirin: Consultancy, Honoraria; Isabl: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; MSKCC: Patents & Royalties.

Background and Objective: Suicide attempts are 10-20X more common than completed suicide and an important risk factor for death by suicide, yet most people who attempt suicide do not die by suicide. The process of recovering after a suicide attempt has not been well studied. The Reasons to go on Living (RTGOL) Project, a narrative web-based study, focuses on experiences of people who have attempted suicide and made the decision to go on living, a process not well studied. Narrative research is ideally suited to understanding personal experiences critical to recovery following a suicide attempt, including the transition to a state of hopefulness. Voices from people with lived experience can help us plan and conceptualize this work. This paper reports on a secondary research question of the larger study: what stories do participants tell of the positive role/impact of the mental health system. Material and Methods: A website created for The RTGOL Project (www.thereasons.ca) enabled participants to anonymously submit a story about their suicide attempt and recovery, a process which enabled participation from a large and diverse group of participants. The only direction given was “if you have made a suicide attempt or seriously considered suicide and now want to go on living, we want to hear from you.” The unstructured narrative format allowed participants to describe their experiences in their own words, to include and emphasize what they considered important. Over 5 years, data analysis occurred in several phases over the course of the study, resulting in the identification of data that were inputted into an Excel file. This analysis used stories where participants described positive involvement with the mental health system (50 stories). Results: Several participants reflected on experiences many years previous, providing the privilege of learning how their life unfolded, what made a difference. Over a five-year period, 50 of 226 stories identified positive experiences with mental health care with sufficient details to allow analysis, and are the focus of this paper. There were a range of suicidal behaviours in these 50 stories, from suicidal ideation only to medically severe suicide attempts. Most described one or more suicide attempts. Three themes identified included: 1) trust and relationship with a health care professional, 2) the role of friends and family and friends, and 3) a wide range of services. Conclusion: Stories open a window into the experiences of the period after a suicide attempt. This study allowed for an understanding of how mental health professionals might help individuals who have attempted suicide write a different story, a life-affirming story. The stories that participants shared offer some understanding of “how” to provide support at a most-needed critical juncture for people as they interact with health care providers, including immediately after a suicide attempt. Results of this study reinforce that just one caring professional can make a tremendous difference to a person who has survived a suicide attempt. Key Words: web-based; suicide; suicide attempt; mental health system; narrative research Word Count: 478 Introduction My Third (or fourth) Suicide AttemptI laid in the back of the ambulance, the snow of too many doses of ativan dissolving on my tongue.They hadn't even cared enough about meto put someone in the back with me,and so, frustrated,I'd swallowed all the pills I had with me— not enough to do what I wanted it to right then,but more than enough to knock me out for a good 14 hours.I remember very little after that;benzodiazepines like ativan commonly cause pre- and post-amnesia, says Google helpfullyI wake up in a locked rooma woman manically drawing on the windows with crayonsthe colors of light through the glassdiffused into rainbows of joy scattered about the roomas if she were coloring on us all,all of the tattered remnants of humanity in a psych wardmade into a brittle mosaic, a quilt of many hues, a Technicolor dreamcoatand I thoughtI am so glad to be able to see this. (Story 187)The nurse opening that door will have a lasting impact on how this story unfolds and on this person’s life. Each year, almost one million people die from suicide, approximately one death every 40 seconds. Suicide attempts are much more frequent, with up to an estimated 20 attempts for every death by suicide.1 Suicide-related behaviours range from suicidal ideation and self-injury to death by suicide. We are unable to directly study those who die by suicide, but effective intervention after a suicide attempt could reduce the risk of subsequent death by suicide. Near-fatal suicide attempts have been used to explore the boundary with completed suicides. Findings indicated that violent suicide attempters and serious attempters (seriousness of the medical consequences to define near-fatal attempts) were more likely to make repeated, and higher lethality suicide attempts.2 In a case-control study, the medically severe suicide attempts group (78 participants), epidemiologically very similar to those who complete suicide, had significantly higher communication difficulties; the risk for death by suicide multiplied if accompanied by feelings of isolation and alienation.3 Most research in suicidology has been quantitative, focusing almost exclusively on identifying factors that may be predictive of suicidal behaviours, and on explanation rather than understanding.4 Qualitative research, focusing on the lived experiences of individuals who have attempted suicide, may provide a better understanding of how to respond in empathic and helpful ways to prevent future attempts and death by suicide.4,5 Fitzpatrick6 advocates for narrative research as a valuable qualitative method in suicide research, enabling people to construct and make sense of the experiences and their world, and imbue it with meaning. A review of qualitative studies examining the experiences of recovering from or living with suicidal ideation identified 5 interconnected themes: suffering, struggle, connection, turning points, and coping.7 Several additional qualitative studies about attempted suicide have been reported in the literature. Participants have included patients hospitalized for attempting suicide8, and/or suicidal ideation,9 out-patients following a suicide attempt and their caregivers,10 veterans with serious mental illness and at least one hospitalization for a suicide attempt or imminent suicide plan.11 Relationships were a consistent theme in these studies. Interpersonal relationships and an empathic environment were perceived as therapeutic and protective, enabling the expression of thoughts and self-understanding.8 Given the connection to relationship issues, the authors suggested it may be helpful to provide support for the relatives of patients who have attempted suicide. A sheltered, friendly environment and support systems, which included caring by family and friends, and treatment by mental health professionals, helped the suicidal healing process.10 Receiving empathic care led to positive changes and an increased level of insight; just one caring professional could make a tremendous difference.11 Kraft and colleagues9 concluded with the importance of hearing directly from those who are suicidal in order to help them, that only when we understand, “why suicide”, can we help with an alternative, “why life?” In a grounded theory study about help-seeking for self-injury, Long and colleagues12 identified that self-injury was not the problem for their participants, but a panacea, even if temporary, to painful life experiences. Participant narratives reflected a complex journey for those who self-injured: their wish when help-seeking was identified by the theme “to be treated like a person”. There has also been a focus on the role and potential impact of psychiatric/mental health nursing. Through interviews with experienced in-patient nurses, Carlen and Bengtsson13 identified the need to see suicidal patients as subjective human beings with unique experiences. This mirrors research with patients, which concluded that the interaction with personnel who are devoted, hope-mediating and committed may be crucial to a patient’s desire to continue living.14 Interviews with individuals who received mental health care for a suicidal crisis following a serious attempt led to the development of a theory for psychiatric nurses with the central variable, reconnecting the person with humanity across 3 phases: reflecting an image of humanity, guiding the individual back to humanity, and learning to live.15 Other research has identified important roles for nurses working with patients who have attempted suicide by enabling the expression of thoughts and developing self-understanding8, helping to see things differently and reconnecting with others,10 assisting the person in finding meaning from their experience to turn their lives around, and maintain/and develop positive connections with others.16 However, one literature review identified that negative attitudes toward self-harm were common among nurses, with more positive attitudes among mental health nurses than general nurses. The authors concluded that education, both reflective and interactive, could have a positive impact.17 This paper is one part of a larger web-based narrative study, the Reasons to go on Living Project (RTGOL), that seeks to understand the transition from making a suicide attempt to choosing life. When invited to tell their stories anonymously online, what information would people share about their suicide attempts? This paper reports on a secondary research question of the larger study: what stories do participants tell of the positive role/impact of the mental health system. The focus on the positive impact reflects an appreciative inquiry approach which can promote better practice.18 Methods Design and Sample A website created for The RTGOL Project (www.thereasons.ca) enabled participants to anonymously submit a story about their suicide attempt and recovery. Participants were required to read and agree with a consent form before being able to submit their story through a text box or by uploading a file. No demographic information was requested. Text submissions were embedded into an email and sent to an account created for the Project without collecting information about the IP address or other identifying information. The content of the website was reviewed by legal counsel before posting, and the study was approved by the local Research Ethics Board. Stories were collected for 5 years (July 2008-June 2013). The RTGOL Project enabled participation by a large, diverse audience, at their own convenience of time and location, providing they had computer access. The unstructured narrative format allowed participants to describe their experiences in their own words, to include and emphasize what they considered important. Of the 226 submissions to the website, 112 described involvement at some level with the mental health system, and 50 provided sufficient detail about positive experiences with mental health care to permit analysis. There were a range of suicidal behaviours in these 50 stories: 8 described suicidal ideation only; 9 met the criteria of medically severe suicide attempts3; 33 described one or more suicide attempts. For most participants, the last attempt had been some years in the past, even decades, prior to writing. Results Stories of positive experiences with mental health care described the idea of a door opening, a turning point, or helping the person to see their situation differently. Themes identified were: (1) relationship and trust with a Health Care Professional (HCP), (2) the role of family and friends (limited to in-hospital experiences), and (3) the opportunity to access a range of services. The many reflective submissions of experiences told many years after the suicide attempt(s) speaks to the lasting impact of the experience for that individual. Trust and Relationship with a Health Care Professional A trusting relationship with a health professional helped participants to see things in a different way, a more hopeful way and over time. “In that time of crisis, she never talked down to me, kept her promises, didn't panic, didn't give up, and she kept believing in me. I guess I essentially borrowed the hope that she had for me until I found hope for myself.” (Story# 35) My doctor has worked extensively with me. I now realize that this is what will keep me alive. To be able to feel in my heart that my doctor does care about me and truly wants to see me get better.” (Story 34). The writer in Story 150 was a nurse, an honours graduate. The 20 years following graduation included depression, hospitalizations and many suicide attempts. “One day after supper I took an entire bottle of prescription pills, then rode away on my bike. They found me late that night unconscious in a downtown park. My heart threatened to stop in the ICU.” Then later, “I finally found a person who was able to connect with me and help me climb out of the pit I was in. I asked her if anyone as sick as me could get better, and she said, “Yes”, she had seen it happen. Those were the words I had been waiting to hear! I quickly became very motivated to get better. I felt heard and like I had just found a big sister, a guide to help me figure out how to live in the world. This person was a nurse who worked as a trauma therapist.” At the time when the story was submitted, the writer was applying to a graduate program. Role of Family and Friends Several participants described being affected by their family’s response to their suicide attempt. Realizing the impact on their family and friends was, for some, a turning point. The writer in Story 20 told of experiences more than 30 years prior to the writing. She described her family of origin as “truly dysfunctional,” and she suffered from episodes of depression and hospitalization during her teen years. Following the birth of her second child, and many family difficulties, “It was at this point that I became suicidal.” She made a decision to kill herself by jumping off the balcony (6 stories). “At the very last second as I hung onto the railing of the balcony. I did not want to die but it was too late. I landed on the parking lot pavement.” She wrote that the pain was indescribable, due to many broken bones. “The physical pain can be unbearable. Then you get to see the pain and horror in the eyes of someone you love and who loves you. Many people suggested to my husband that he should leave me in the hospital, go on with life and forget about me. During the process of recovery in the hospital, my husband was with me every day…With the help of psychiatrists and a later hospitalization, I was actually diagnosed as bipolar…Since 1983, I have been taking lithium and have never had a recurrence of suicidal thoughts or for that matter any kind of depression.” The writer in Story 62 suffered childhood sexual abuse. When she came forward with it, she felt she was not heard. Self-harm on a regular basis was followed by “numerous overdoses trying to end my life.” Overdoses led to psychiatric hospitalizations that were unhelpful because she was unable to trust staff. “My way of thinking was that ending my life was the only answer. There had been numerous attempts, too many to count. My thoughts were that if I wasn’t alive I wouldn’t have to deal with my problems.” In her final attempt, she plunged over the side of a mountain, dropping 80 feet, resulting in several serious injuries. “I was so angry that I was still alive.” However, “During my hospitalization I began to realize that my family and friends were there by my side continuously, I began to realize that I wasn't only hurting myself. I was hurting all the important people in my life. It was then that I told myself I am going to do whatever it takes.” A turning point is not to say that the difficulties did not continue. The writer of Story 171 tells of a suicide attempt 7 years previous, and the ongoing anguish. She had been depressed for years and had thoughts of suicide on a daily basis. After a serious overdose, she woke up the next day in a hospital bed, her husband and 2 daughters at her bed. “Honestly, I was disappointed to wake up. But, then I saw how scared and hurt they were. Then I was sorry for what I had done to them. Since then I have thought of suicide but know that it is tragic for the family and is a hurt that can never be undone. Today I live with the thought that I am here for a reason and when it is God's time to take me then I will go. I do believe living is harder than dying. I do believe I was born for a purpose and when that is accomplished I will be released. …Until then I try to remind myself of how I am blessed and try to appreciate the wonders of the world and the people in it.” Range of Services The important role of mental health and recovery services was frequently mentioned, including dialectical behavioural therapy (DBT)/cognitive-behavioural therapy (CBT), recovery group, group therapy, Alcoholics Anonymous, accurate diagnosis, and medications. The writer in Story 30 was 83 years old when she submitted her story, reflecting on a life with both good and bad times. She first attempted suicide at age 10 or 12. A serious post-partum depression followed the birth of her second child, and over the years, she experienced periods of suicidal intent: “Consequently, a few years passed and I got to feeling suicidal again. I had pills in one pocket and a clipping for “The Recovery Group” in the other pocket. As I rode on the bus trying to make up my mind, I decided to go to the Recovery Group first. I could always take the pills later. I found the Recovery Group and yoga helpful; going to meetings sometimes twice a day until I got thinking more clearly and learned how to deal with my problems.” Several participants described the value of CBT or DBT in learning to challenge perceptions. “I have tools now to differentiate myself from the illness. I learned I'm not a bad person but bad things did happen to me and I survived.”(Story 3) “The fact is that we have thoughts that are helpful and thoughts that are destructive….. I knew it was up to me if I was to get better once and for all.” (Story 32): “In the hospital I was introduced to DBT. I saw a nurse (Tanya) every day and attended a group session twice a week, learning the techniques. I worked with the people who wanted to work with me this time. Tanya said the same thing my counselor did “there is no study that can prove whether or not suicide solves problems” and I felt as though I understood it then. If I am dead, then all the people that I kept pushing away and refusing their help would be devastated. If I killed myself with my own hand, my family would be so upset. DBT taught me how to ‘ride my emotional wave’. ……….. DBT has changed my life…….. My life is getting back in order now, thanks to DBT, and I have lots of reasons to go on living.”(Story 19) The writer of Story 67 described the importance of group therapy. “Group therapy was the most helpful for me. It gave me something besides myself to focus on. Empathy is such a powerful emotion and a pathway to love. And it was a huge relief to hear others felt the same and had developed tools of their own that I could try for myself! I think I needed to learn to communicate and recognize when I was piling everything up to build my despair. I don’t think I have found the best ways yet, but I am lifetimes away from that teenage girl.” (Story 67) The author of story 212 reflected on suicidal ideation beginning over 20 years earlier, at age 13. Her first attempt was at 28. “I thought everyone would be better off without me, especially my children, I felt like the worst mum ever, I felt like a burden to my family and I felt like I was a failure at life in general.” She had more suicide attempts, experienced the death of her father by suicide, and then finally found her doctor. “Now I’m on meds for a mood disorder and depression, my family watch me closely, and I see my doctor regularly. For the first time in 20 years, I love being a mum, a sister, a daughter, a friend, a cousin etc.” Discussion The 50 stories that describe positive experiences in the health care system constitute a larger group than most other similar studies, and most participants had made one or more suicide attempts. Several writers reflected back many years, telling stories of long ago, as with the 83-year old participant (Story 30) whose story provided the privilege of learning how the author’s life unfolded. In clinical practice, we often do not know – how did the story turn out? The stories that describe receiving health care speak to the impact of the experience, and the importance of the issues identified in the mental health system. We identified 3 themes, but it was often the combination that participants described in their stories that was powerful, as demonstrated in Story 20, the young new mother who had fallen from a balcony 30 years earlier. Voices from people with lived experience can help us plan and conceptualize our clinical work. Results are consistent with, and add to, the previous work on the importance of therapeutic relationships.8,10,11,14–16 It is from the stories in this study that we come to understand the powerful experience of seeing a family members’ reaction following a participant’s suicide attempt, and how that can be a potent turning point as identified by Lakeman and Fitzgerald.7 Ghio and colleagues8 and Lakeman16 identified the important role for staff/nurses in supporting families due to the connection to relationship issues. This research also calls for support for families to recognize the important role they have in helping the person understand how much they mean to them, and to promote the potential impact of a turning point. The importance of the range of services reflect Lakeman and Fitzgerald’s7 theme of coping, associating positive change by increasing the repertoire of coping strategies. These findings have implications for practice, research and education. Working with individuals who are suicidal can help them develop and tell a different story, help them move from a death-oriented to life-oriented position,15 from “why suicide” to “why life.”9 Hospitalization provides a person with the opportunity to reflect, to take time away from “the real world” to consider oneself, the suicide attempt, connections with family and friends and life goals, and to recover physically and emotionally. Hospitalization is also an opening to involve the family in the recovery process. The intensity of the immediate period following a suicide attempt provides a unique opportunity for nurses to support and coach families, to help both patients and family begin to see things differently and begin to create that different story. In this way, family and friends can be both a support to the person who has attempted suicide, and receive help in their own struggles with this experience. It is also important to recognize that this short period of opportunity is not specific to the nurses in psychiatric units, as the nurses caring for a person after a medically severe suicide attempt will frequently be the nurses in the ICU or Emergency departments. Education, both reflective and interactive, could have a positive impact.17 Helping staff develop the attitudes, skills and approach necessary to be helpful to a person post-suicide attempt is beginning to be reported in the literature.21 Further implications relate to nursing curriculum. Given the extent of suicidal ideation, suicide attempts and deaths by suicide, this merits an important focus. This could include specific scenarios, readings by people affected by suicide, both patients themselves and their families or survivors, and discussions with individuals who have made an attempt(s) and made a decision to go on living. All of this is, of course, not specific to nursing. All members of the interprofessional health care team can support the transition to recovery of a person after a suicide attempt using the strategies suggested in this paper, in addition to other evidence-based interventions and treatments. Findings from this study need to be considered in light of some specific limitations. First, the focus was on those who have made a decision to go on living, and we have only the information the participants included in their stories. No follow-up questions were possible. The nature of the research design meant that participants required access to a computer with Internet and the ability to communicate in English. This study does not provide a comprehensive view of in-patient care. However, it offers important inputs to enhance other aspects of care, such as assessing safety as a critical foundation to care. We consider these limitations were more than balanced by the richness of the many stories that a totally anonymous process allowed. Conclusion Stories open a window into the experiences of a person during the period after a suicide attempt. The RTGOL Project allowed for an understanding of how we might help suicidal individuals change the script, write a different story. The stories that participants shared give us some understanding of “how” to provide support at a most-needed critical juncture for people as they interact with health care providers immediately after a suicide attempt. While we cannot know the experiences of those who did not survive a suicide attempt, results of this study reinforce that just one caring professional can make a crucial difference to a person who has survived a suicide attempt. We end with where we began. Who will open the door? References 1. World Health Organization. Suicide prevention and special programmes. http://www.who.int/mental_health/prevention/suicide/suicideprevent/en/index.html Geneva: Author; 2013.2. Giner L, Jaussent I, Olie E, et al. Violent and serious suicide attempters: One step closer to suicide? J Clin Psychiatry 2014:73(3):3191–197.3. Levi-Belz Y, Gvion Y, Horesh N, et al. Mental pain, communication difficulties, and medically serious suicide attempts: A case-control study. Arch Suicide Res 2014:18:74–87.4. Hjelmeland H and Knizek BL. Why we need qualitative research in suicidology? Suicide Life Threat Behav 2010:40(1):74–80.5. Gunnell D. A population health perspective on suicide research and prevention: What we know, what we need to know, and policy priorities. Crisis 2015:36(3):155–60.6. Fitzpatrick S. Looking beyond the qualitative and quantitative divide: Narrative, ethics and representation in suicidology. Suicidol Online 2011:2:29–37.7. Lakeman R and FitzGerald M. How people live with or get over being suicidal: A review of qualitative studies. J Adv Nurs 2008:64(2):114–26.8. Ghio L, Zanelli E, Gotelli S, et al. Involving patients who attempt suicide in suicide prevention: A focus group study. J Psychiatr Ment Health Nurs 2011:18:510–18.9. Kraft TL, Jobes DA, Lineberry TW., Conrad, A., & Kung, S. Brief report: Why suicide? Perceptions of suicidal inpatients and reflections of clinical researchers. Arch Suicide Res 2010:14(4):375-382.10. Sun F, Long A, Tsao L, et al. The healing process following a suicide attempt: Context and intervening conditions. Arch Psychiatr Nurs 2014:28:66–61.11. Montross Thomas L, Palinkas L, et al. Yearning to be heard: What veterans teach us about suicide risk and effective interventions. Crisis 2014:35(3):161–67.12. Long M, Manktelow R, and Tracey A. The healing journey: Help seeking for self-injury among a community population. Qual Health Res 2015:25(7):932–44.13. Carlen P and Bengtsson A. Suicidal patients as experienced by psychiatric nurses in inpatient care. Int J Ment Health Nurs 2007:16:257–65.14. Samuelsson M, Wiklander M, Asberg M, et al. Psychiatric care as seen by the attempted suicide patient. J Adv Nurs 2000:32(3):635–43.15. Cutcliffe JR, Stevenson C, Jackson S, et al. A modified grounded theory study of how psychiatric nurses work with suicidal people. Int J Nurs Studies 2006:43(7):791–802.16. Lakeman, R. What can qualitative research tell us about helping a person who is suicidal? Nurs Times 2010:106(33):23–26.17. Karman P, Kool N, Poslawsky I, et al. Nurses’ attitudes toward self-harm: a literature review. J Psychiatr Ment Health Nurs 2015:22:65–75.18. Carter B. ‘One expertise among many’ – working appreciatively to make miracles instead of finding problems: Using appreciative inquiry as a way of reframing research. J Res Nurs 2006:11(1): 48–63.19. Lieblich A, Tuval-Mashiach R, Zilber T. Narrative research: Reading, analysis, and interpretation. Sage Publications; 1998.20. Braun V and Clarke V. Using thematic analysis in psychology. Qual Res Psychol 2006:3(2):77–101.21. Kishi Y, Otsuka K, Akiyama K, et al. Effects of a training workshop on suicide prevention among emergency room nurses. Crisis 2014:35(5):357–61.

Background and Objectives: Marriage has always been considered as the starting point of the family and hence is a complex and very delicate form of human relationship. Commitment is one of the critical predictors of an individuals' willingness to stay in a marriage and a determinant factor regarding its time and quality. In this regard, the present study aimed to compare the effectiveness of imago relationship therapy (IRT) and Feldman's integrated approach on marital commitment in conflicting couples in Tehran, Iran. Materials and Methods: This quasi-experimental applied research was conducted based on a pre-test, post-test, and follow-up design with a control group. The statistical population of this study included all of the conflicted couples who referred to the Department of Women's Affairs in the Post Bank of the District 6 of Tehran municipality and a Psychological Clinic in the District 22 of Tehran municipality in 2018. In total, 30 couples were enrolled in the study who were equally divided into two groups of intervention and control. The required data were collected using the marital conflict questionnaire developed by Barati and Sanei (1998) and marital commitment questionnaire developed by Adams and Jones (1997). Moreover, the collected data were analyzed using the analysis of covariance. Results: Based on the results, both the IRT and Feldman's integrated approach affected the personal (F=27.63, P<0.001), ethical (F=69.70, P<0.001), and structural commitment (F=40.51, P<0.001). Nevertheless, IRT affected marital commitment more than the Feldman's integrated approach. Conclusion: It can be concluded that IRT and Feldman's integrated approach can improve the marital commitment of conflicting couples.

The only couple therapy model that has published positive outcome studies is Emotionally Focused Therapy (Johnson SM & Talitman E, 1997); (Johnson SM, Williams-Keeler L, 1998). This paper review the merits and limitations of some popular couple therapy models including most that do not have any published outcome studies and formulate a new model of couple and individual psychotherapy that integrates the merits of a number of the models without their limitations. The model although is primarily that of couple therapy is also of individual psychotherapy because it takes the view that all individuals live in the context of a relationship and are relational being (Siegel, 2010). Specifically the transference and countertransference of developmental materials components of the Imago therapy model (Hendrix, H., 1996) together with the dysfunctional developmental schemas (Couple Schema Therapy; Simeone-Difrancesco, C., Roediger, E., & Stevens, B. A., 2015) that bring couples together is dramatized by couples facilitated safely by the therapist in the new model of Couple Drama Therapy. In doing so it is shown that couples attain insight quickly (within just 1 or 2 sessions) of each other’s developmental needs and are motivated to meet these needs thereby transforming and healing the dysfunctional schemas into healthy adults schemas.

Introduction: The prevalence of dental anxiety appears to be relatively consistent throughout the world, but some studies reports higher levels than others. This may be related to different instruments used. Objective: to identify and describe the main instruments used in the assessment of dental anxiety in adolescents. Material and Methods: Literature review. Original studies involving adolescents, in which the methodology comprised the application of some instrument to identify and / or quantify the phenomenon, were included. The search was limited to English, Portuguese and Spanish publications in the period between 2012 and 2016. Reviews, Meta-analyzes and case reports were excluded. The selected databases were MEDLINE (via PubMed) and LILACS (via BVS); and the search was developed with the following descriptors: 'dental anxiety', 'adolescents', 'Surveys and Questionnaires' (MeSH), combined by the Boolean operator AND. Results: Ten psychometric instruments are available to assess dental anxiety. The most frequently used instrument is the Dental Anxiety Scale (DAS), presented in nine studies. Less frequently used is the Facial Image Scale (FIS), presented in only one investigation. Most of the instruments affords translations into other languages, including Portuguese. Conclusion: The most used instrument is the DAS, followed by its modified version, the MDAS. Usually, more than one instrument has been used to correlate the findings and to provide the measured construct a greater consistency.Descriptors: Dental Anxiety; Adolescent; Surveys and Questionnaires.ReferencesStenebrand A, Wide Boman U, Hakeberg M. Dental anxiety and symptoms of general anxiety and depression in 15‐year‐olds. Int J Dent Hyg. 2013; 11(2):99-104.American Psychiatric Association. DSM-5: Manual diagnóstico e estatístico de transtornos mentais. São Paulo:Artmed; 2014.Folayan MO, Idehen EE, Ojo OO. 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