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Definitive radiation therapy with concurrent chemotherapy is curative for nonmetastatic squamous cell carcinoma of the anus (SCCA). However, the true effect of chemoradiation on long-term functional outcomes is poorly understood owing to limited follow-up and patient-reported outcomes (PROs).We conducted a cross-sectional survey of 248 patients with SCCA treated with definitive intensity modulated radiation and concurrent chemotherapy from 2010 to 2018 who were alive and without recurrence. PRO measures were collected, including Functional Assessment of Cancer Therapy-General (FACT-G7), Fecal Incontinence Quality of Life (FIQoL), Low Anterior Resection Syndrome (LARS), and International Consultation on Incontinence Questionnaires (ICIQ). Models were used to determine the association between demographic, tumor, treatment, and dosimetric data with PROs.One hundred twelve (45%) patients completed PROs. Median [interquartile range (IQR)] time from radiation completion to survey was 51 [37-85] months. The median scores [IQR] for FACT-G7, FIQoL, and LARS were 21 [15-24], 14 [11-16], and 32 [25-37], respectively. For men, median subscores [IQR] for ICIQ voiding and incontinence subscores were 5 [2-6] and 1 [1-3], respectively. For women, median subscores [IQR] for ICIQ voiding, incontinence, and filling were 1 [1-3], 5 [3-8], and 4 [2-5], respectively. Higher (better) FIQoL scores were associated with higher (better) FACT-G7 scores (β = 0.83; 95% confidence interval, 0.58-1.09; P.001), and higher (worse) LARS scores were associated with lower (worse) FACT-G7 scores (β = -0.22; 95% confidence interval, -0.31 to -0.13; P.001). A separate multivariable analysis revealed higher bowel bag D1% was associated with lower (worse) FIQoL (P = .001) and higher (worse) LARS (P = .003) scores. Higher bladder V40 Gy was associated with increased (worse) ICIQ voiding subscore (P = .001).Patients treated with modern chemoradiation for SCCA experience significant long-term bowel toxic effects with considerable effect on quality of life. Minimizing bowel hotspots and bladder V40 Gy may improve bowel and urinary function. Other interventions to reduce long-term toxic effects and improve quality of life are needed.

PDF - 3969K, Supplemental Figure 1. Therapeutic inhibition of SFKs can block nEGFR translocation in colorectal tumor models.

PDF - 69K, Legend for Supplementary Figure 1.

Supplemental Figure 2. HNSCC cell proliferation and apoptosis are not significantly impacted 24 hours post R428 treatment

Supplemental Table 3. Fractional cell proliferation analysis for drug combination synergy

Supplemental Table 1. Clinical information describing HNSCC cohort

Supplemental Figure 3. Genetic ablation of AXL enhances HNSCC cell line response to cisplatin, cetuximab, and radiation

Supplemental Figure Legends

Supplemental Figure 1. AXL knockdown inhibits the migration of HNSCC cell lines

Supplemental Materials and Methods

Supplemental Table 2. Clinical parameters and median progression-free survival in relation to AXL expression among patients with HNSCC

Supplemental Table 4. Clinical characteristics of patients prior to surgery and PDX establishment

Purpose: Head and neck squamous cell carcinoma (HNSCC) represents the eighth most common malignancy worldwide. Standard-of-care treatments for patients with HNSCC include surgery, radiation, and chemotherapy. In addition, the anti-EGFR monoclonal antibody cetuximab is often used in combination with these treatment modalities. Despite clinical success with these therapeutics, HNSCC remains a difficult malignancy to treat. Thus, identification of new molecular targets is critical.Experimental Design: In the current study, the receptor tyrosine kinase AXL was investigated as a molecular target in HNSCC using established cell lines, HNSCC patient-derived xenografts (PDX), and human tumors. HNSCC dependency on AXL was evaluated with both anti-AXL siRNAs and the small-molecule AXL inhibitor R428. Furthermore, AXL inhibition was evaluated with standard-of-care treatment regimens used in HNSCC.Results: AXL was found to be highly overexpressed in several models of HNSCC, where AXL was significantly associated with higher pathologic grade, presence of distant metastases, and shorter relapse-free survival in patients with HNSCC. Further investigations indicated that HNSCC cells were reliant on AXL for cellular proliferation, migration, and invasion. In addition, targeting AXL increased HNSCC cell line sensitivity to chemotherapy, cetuximab, and radiation. Moreover, radiation-resistant HNSCC cell line xenografts and PDXs expressed elevated levels of both total and activated AXL, indicating a role for AXL in radiation resistance.Conclusions: This study provides evidence for the role of AXL in HNSCC pathogenesis and supports further preclinical and clinical evaluation of anti-AXL therapeutics for the treatment of patients with HNSCC. Clin Cancer Res; 21(11); 2601–12. ©2015 AACR.

Supplemental Materials and Methods. Supplemental materials and methods including qPCR primers and in vivo PDX establishment and characterization.

BackgroundYoung adults and other working-age adults with cancer are at risk for cancer-related financial toxicity (FT), including material hardships, depletion of coping resources, and psychological burden. This study compares FT domains in young adults (18-39years old) (YAs), other working-age adults (40-64years old), and older adults (≥65years old) receiving cancer care.MethodsA total of 311 adults were surveyed using the multi-domain Economic Strain and Resilience in Cancer instrument measuring FT (0-10 score indicating least to greatest FT; score ≥5 severe FT). Participants were receiving ambulatory care from March-September 2019. Associations of age with overall FT and material hardship, coping resource depletion, and psychological burden FT domains were tested using Kruskal-Wallis and χ2 tests and multivariable generalized linear models with gamma distribution.ResultsYAs (median age, 31.5years) comprised 9.6% of the sample; other working-age adults comprised 56.9%. Overall, material, coping, and psychological FT scores were worse in younger age adults versus older adults (P&nbsp

Purpose Quality assurance (QA) practices improve the quality level of oncology trials by ensuring that the protocol is followed and the results are valid and reproducible. This study investigated the utilization of QA among randomized controlled trials that involve radiotherapy (RT). Methods and Materials We searched ClinicalTrials.gov in February 2020 for all phase III oncology randomized clinical trials (RCTs). These trials were screened for RT-specific RCTs that had published primary trial results. Information regarding QA in each trial was collected from the study publications and trial protocol if available. Two individuals independently performed trial screening and data collection. Pearson’s Chi-square tests analyses were used to assess factors that were associated with QA inclusion in RT trials. Results Forty-two RCTs with RT as the primary intervention or as a mandatory component of the protocol were analyzed; the earliest was started in 1994 and one trial was still active though not recruiting. Twenty-nine (69%) trials mandated RT quality assurance (RTQA) practices as part of the trial protocol, with 19 (45%) trials requiring institutional credentialing. Twenty-one (50%) trials published protocol deviation outcomes. Clinical trials involving advanced radiation techniques (IMRT, VMAT, SRS, SBRT) did not include more RTQA than trials without these advanced techniques (73% vs. 65%, p=0.55). Trials that reported protocol deviation outcomes were associated with mandating RTQA in their protocols as compared to trials that did not report these outcomes (100% vs. 38%, p Conclusions There is a lack of RTQA utilization and transparency in RT clinical trials. It is imperative for RT trials to include increased QA for safe, consistent, and high-quality RT planning and delivery.

PurposeIn order to improve segmentation accuracy in head and neck cancer (HNC) radiotherapy treatment planning for the 1.5T MR-Linac, 3D fat-suppressed T2-weighted MRI sequences were developed and optimized.MethodsAfter initial testing of fat suppression techniques, SPectral Attenuated Inversion Recovery (SPAIR) was chosen as the fat suppression technique. Five candidate SPAIR sequences and a non-suppressed T2-weighted sequence were acquired on five HNC patients on the Unity MR-Linac. The primary tumor, metastatic lymph nodes, parotid glands, and pterygoid muscles were delineated by five segmentors. A robust image quality analysis platform was developed to objectively score the SPAIR sequences based on a combination of qualitative and quantitative metrics.ResultsSequences were analyzed for signal-to-noise (SNR), contrast-to-noise (CNR) compared to fat and muscle, conspicuity, pairwise distance metrics, segmentor assessment, and MR physicist assessment. From this analysis, the non-suppressed sequence was inferior to each of the SPAIR sequences for the primary tumor, lymph nodes, and parotid glands, but was superior for the pterygoid muscles. Two SPAIR sequences consistently received the highest scores among the analysis categories and are recommended for use to Unity MR-Linac users for HNC radiotherapy treatment planning.ConclusionsTwo deliverables resulted from this study. First, an optimized 3D fat-suppressed T2-weighted sequence was developed that can be disseminated to Unity MR-Linac users. Second, a robust image quality analysis process pathway, used to objectively score the various SPAIR sequences, was developed and can be customized and generalized to any image quality optimization. Improved segmentation accuracy with the proposed SPAIR sequence can potentially lead to improved treatment outcomes and reduced toxicity by maximizing target coverage and minimizing organ-at-risk exposure.

To date, the optimal management of displaced midshaft clavicle fractures remains unknown. Operatively, plate or nail fixation may be used. Nonoperatively, the options are sling or harness. Given the equivocal effectiveness between approaches, the costs to the health care system and the patient become critical considerations. A decision tree model was constructed to study plate and sling management of displaced midshaft clavicle fractures. Primary analysis used 6 randomized controlled trials that directly compared open reduction and internal fixation with a plate to sling. Secondary analysis included 18 studies that studied either plate, sling, or both. Incremental cost-effectiveness ratios (ICERs) were calculated using quality-adjusted life-years (QALYs). Second-order Monte Carlo probabilistic sensitivity analysis (PSA) was subsequently conducted. In primary analysis, at a willingness-to-pay (WTP) threshold of $100,000, operative management was found to be less cost-effective relative to nonoperative management, with an ICER of $606,957/QALY (0.03 additional QALYs gained for an additional $16,120). In PSA, sling management was cost-effective across all WTP ranges. In secondary analysis, the ICER decreased to $75,230/QALY. Primary analysis shows that plate management is not a cost-effective option. In secondary analysis, the incremental effectiveness of plate management increased enough that the calculated ICER is below the WTP threshold of $100,000; however, the strength of evidence in secondary analysis is lower than in primary analysis. Thus, because neither option is dominant in this model, both plate and sling remain viable approaches, although the cost-conscious decision will be to treat these fractures with a sling until future data suggest otherwise. [ Orthopedics . 2022;45(5):e243–e251.]

OBJECTIVES: People living with HIV (PLWH) have increased risk for cancer and worse cancer-specific survival. We explored the emotional burden of cancer and HIV as a potential driver of cancer mortality. RESEARCH APPROACH: Semi-structured qualitative interviews with PLWH and cancer. PARTICIPANTS: 27 PLWH who had either completed cancer treatment, were currently undergoing treatment, or experienced challenges in completing treatment. METHODOLOGICAL APPROACH: An inductive qualitative approach using the constant comparative method. FINDINGS: Participants drew strong parallels between being diagnosed with HIV and cancer. Many described HIV-related stigma that hindered social support. Cancer treatment side effects were a major challenge, impacting treatment adherence for both cancer and HIV. IMPLICATIONS FOR PSYCHOSOCIAL PROVIDERS: There is a need for convenient, affordable, and visible services to support PLHIV as they navigate cancer care. Services should be tailored to the unique needs of this population by addressing HIV-related stigma, building social support, and fostering resilience.

Single-institution studies have shown the oncologic benefit of ablative liver radiotherapy (A-RT) for patients with unresectable intrahepatic cholangiocarcinoma (ICC). However, adoption of A-RT across the United States and its associated outcomes are unknown.We queried the National Cancer Data Base for nonsurgically managed patients with ICC diagnosed between 2004 and 2018. Patients were labeled A-RT for receipt of biologically effective doses (BEDOf 27,571 patients, the most common treatments were chemotherapy without liver RT (45%), no chemotherapy or liver RT (42%), and liver RT ± chemotherapy (13%). Use of liver RT remained constant over time. Of 1112 patients receiving liver RT with known doses, RT was 73% Conv-RT (median BEDAlthough A-RT has been increasingly used, use of liver RT as a whole in the United States remained constant despite growing evidence supporting its use, suggesting continued unmet need. A-RT is associated with longer survival versus Conv-RT.Bile duct cancer is a rare, deadly disease that often presents at advanced stages. Single-institution retrospective studies have demonstrated that use of high-dose radiotherapy may be associated with longer survival, but larger studies have not been conducted. We used a large, national cancer registry of patients diagnosed between 2004 and 2018 to show that liver radiotherapy use remains low in the United States, despite growing evidence that patients who receive it live longer. Furthermore, we showed that patients who received high-dose radiotherapy lived longer than those who received lower doses. Greater awareness of the benefits of liver radiotherapy is needed to improve patient outcomes.

Purpose: People living with HIV are less likely to receive cancer treatment and have worse cancer-specific survival, yet underlying drivers of this disparity have minimally been explored. We investigated cancer care barriers from the perspective of patients living with HIV and cancer (PLWHC) to inform future interventions, reduce disparities, and improve outcomes. Methods: We conducted in-depth semistructured interviews with 27 PLWHC. The interview guide explored perceptions of the cancer care experience, treatment decision making, and barriers to cancer treatment. Interview data were analyzed using the constant comparative method of qualitative analysis. Results: Study participants were predominantly men (n=22, 81%) with a median age of 56 years and median annual income of $24,000. Among those who experienced challenges with cancer treatment adherence, barriers included debilitating side effects of cancer treatment, stigma surrounding HIV, issues with coping and mental health, the financial burden of cancer care, and challenges with care accessibility. Despite these challenges, participants indicated that their past experiences of coping with HIV had prepared them to accept and address their cancer diagnosis. Resiliency and social support were key facilitators for cancer treatment adherence. Conclusion: This qualitative study of PLWHC in the United States found that a cancer diagnosis created a substantial added stress to an already challenging situation. Health- and stigma-related stressors impacted patients' ability to fully complete cancer treatment as prescribed. There is a need for improved provider communication and mental health support for PLWHC to ensure equitable access to and completion of cancer treatment.

We have previously shown that ablative radiotherapy (A-RT) with a biologically effective dose (BED10) ≥ 80.5 Gy for patients with unresectable intrahepatic cholangiocarcinoma (ICC) is associated with longer survival. Despite recent large-scale sequencing efforts in ICC, outcomes following RT based on genetic alterations have not been described. We reviewed records of 156 consecutive patients treated with A-RT for unresectable ICC from 2008 to 2020. For 114 patients (73%), next-generation sequencing provided molecular profiles. The overall survival (OS), local control (LC), and distant metastasis-free survival (DMFS) were estimated using the Kaplan–Meier method. Univariate and multivariable Cox analyses were used to determine the associations with the outcomes. The median tumor size was 7.3 (range: 2.2–18.2) cm. The portal vein thrombus (PVT) was present in 10%. The RT median BED10 was 98 Gy (range: 81–144 Gy). The median (95% confidence interval) follow-up was 58 (42–104) months from diagnosis and 39 (33–74) months from RT. The median OS was 32 (29–35) months after diagnosis and 20 (16–24) months after RT. The one-year OS, LC, and intrahepatic DMFS were 73% (65–80%), 81% (73–87%), and 34% (26–42%). The most common mutations were in IDH1 (25%), TP53 (22%), ARID1A (19%), and FGFR2 (13%). Upon multivariable analysis, the factors associated with death included worse performance status, larger tumor, metastatic disease, higher CA 19-9, PVT, satellitosis, and IDH1 and PIK3CA mutations. TP53 mutation was associated with local failure. Further investigation into the prognostic value of individual mutations and combinations thereof is warranted.

This review highlights the considerations of the radiation oncologist when managing patients with inflammatory breast cancer (IBC) as well as the radiation oncologist's role as a member of the multi-disciplinary team.IBC makes up only 1-4% of all breast cancer diagnoses but incidence is increasing. IBC is diagnosed based on a constellation of clinical features, including the rapid onset of breast erythema and edema (peau d'orange) of one-third or more of the skin of the breast and with a palpable border to the edema. Most published IBC local-regional control rates are consistently lower than those observed in non-IBC, which the highlights the need for deliberate treatment techniques to maximize clinical outcomes.For this narrative review, we discuss the principles of radiation target delineation and dose escalation; highlight new findings in the local-regional management of IBC; provide a critical evaluation of the recent literature evaluating local-regional treatment of IBC; and offer a brief introduction to possible future directions regarding the optimal treatment and management of IBC based on our institutional experience.IBC is an aggressive type of breast cancer that warrants multi-disciplinary care from breast surgical, medical, and radiation oncology. Several strategies exist to enhance the effect of radiation therapy (RT) on local-regional control, including hyperfractionation, use of bolus, increased total RT dose, and radiosensitizers, which are currently being tested in randomized trials. With an individualized patient approach, local-regional control rates are improving for IBC.

Male breast cancer treatment regimens are often extrapolated from female-based studies because of a paucity of literature analyzing male breast cancer. Using ClinicalTrials.gov, we analyzed breast cancer randomized clinical trials (RCTs) to determine which factors were associated with male-gender inclusion. Of 131 breast cancer RCTs identified, male patients represented 0.087% of the total study population, which is significantly less than the proportion of male patients with breast cancer in the U.S. (0.95%; p < .001). Twenty-seven trials included male patients (20.6%). Lower rates of male inclusion were seen in trials that randomized or mandated hormone therapy as part of the trial protocol compared with trials that did not randomize or mandate endocrine therapy (2.5% vs. 28.6% male inclusion; p < .001). It is imperative for breast cancer clinical trials to include men when allowable in order to improve generalizability and treatment decisions in male patients with breast cancer.

BACKGROUND To the authors' knowledge, little is known regarding the impact of the Patient Protection and Affordable Care Act (ACA) on people living with HIV and cancer (PLWHC), who have lower cancer treatment rates and worse cancer outcomes. To investigate this research gap, the authors examined the effects of the ACA on insurance coverage and receipt of cancer treatment among PLWHC in the United States. METHODS HIV-infected individuals aged 18 to 64 years old with cancer diagnosed between 2011 and 2015 were identified in the National Cancer Data Base. Health insurance coverage and cancer treatment receipt were compared before and after implementation of the ACA in non-Medicaid expansion and Medicaid expansion states using difference-in-differences analysis. RESULTS Of the 4794 PLWHC analyzed, approximately 49% resided in nonexpansion states and were more often uninsured (16.7% vs 4.2%), nonwhite (65.2% vs 60.2%), and of low income (36.3% vs 26.9%) compared with those in Medicaid expansion states. After 2014, the percentage of uninsured individuals decreased in expansion states (from 4.9% to 3%; P = .01) and nonexpansion states (from 17.6% to 14.6%; P = .06), possibly due to increased Medicaid coverage in expansion states (from 36.9% to 39.2%) and increased private insurance coverage in nonexpansion states (from 29.5% to 34.7%). There was no significant difference in cancer treatment receipt noted between Medicaid expansion and nonexpansion states. However, the percentage of PLWHC treated at academic facilities increased significantly only in expansion states (from 40.2% to 46.7% [P

BACKGROUND: People with the human immunodeficiency virus (PWHIV) have improved survival because of the advent of antiretroviral therapy. Consequently, PWHIV experience higher rates of non-acquired immunodeficiency syndrome-defining malignancies (NADMs). Previous studies have demonstrated worsened cancer-specific survival in PWHIV, partly because of advanced cancer stage at diagnosis. The objective of the current systematic review was to evaluate screening disparities for NADMs among PWHIV. METHODS: The PubMed, Cochrane, EMBASE, and ClinicalTrials.gov databases were searched from January 1, 1996 through April 10, 2018 to identify studies related to screening disparities for NADMs among PWHIV. Eligibility criteria included any study performed in a high-income country that compared screening for NADMs by HIV status. After title/abstract screening and full-text review, articles that met eligibility criteria were analyzed. RESULTS: Of 613 unique articles identified through the search, 9 studies were analyzed. Three studies addressed breast cancer screening, 4 addressed colorectal cancer screening, and 2 addressed prostate cancer screening. Five of the reviewed studies demonstrated that PWHIV were less likely to receive indicated cancer screenings compared with the general population, whereas 3 indicated that screening proportions were higher among PWHIV, and 1 demonstrated that screening proportions were comparable. In most of the studies, PWHIV who had regular access to health care were more likely to undergo cancer screening. CONCLUSIONS: The available evidence does not uniformly confirm that PWHIV are less likely to receive cancer screening. Social determinants of health (insurance status, access to health care, education, income level) were associated with the receipt of appropriate cancer screening, suggesting that these barriers need to be addressed to improve cancer screening in PWHIV.

PURPOSE/OBJECTIVE(S) Few studies have long-term follow-up assessing patient-reported outcomes (PROs) after intensity-modulated radiation therapy (IMRT)-based chemoradiation (CRT) for squamous cell carcinoma of the anus (SCCA). There is poor agreement between physician-graded toxicity and PROs regarding quality of life (QOL) in patients with SCCA. Therefore, we surveyed SCCA survivors ≥ 2 years out from CRT with validated PRO instruments assessing bowel, bladder, and sexual function. MATERIALS/METHODS We identified 248 patients with SCCA treated with definitive IMRT-based CRT at a large tertiary cancer center from 2010-2018, who were alive and without recurrence. Patients were asked to complete five PRO instruments: Fecal Incontinence QOL Scale (FIQOL), Low Anterior Resection Syndrome Score (LARS), International Consultation on Incontinence Questionnaire (ICIQ), male and female lower urinary tract symptoms (MLUTS and FLUTS, respectively), International Index of Erectile Function (IIEF), and Female Sexual Function Index (FSFI). FIQOL, LARS, IIEF, and FSFI scores were dichotomized and logistic regression used to identify predictors of QOL scores. RESULTS One hundred eight (44%) patients completed the PROs. Respondents' median [interquartile range, (IQR)] age was 66 [59-72] years, 80% were female, and 95% were white. Median [IQR] gross tumor volume (GTV) was 45 [27-71] cc; dose to GTV was 50 Gray (Gy), 54 Gy and 58 Gy in 25%, 53%, and 22%, respectively. Median [IQR] time from CRT was 51 [37-84] months. Median [IQR] FIQOL score was 14.3/20 [11.2-16.1]; higher is better. Larger GTV size (OR 0.99; P = 0.03) was associated with lower FIQOL score. Sixty-one (56%) patients met major LARS criteria. There was a trend towards a higher incidence of major LARS with GTV dose ≥ 54 Gy (OR 2.39; P = 0.08). Men had median [IQR] ICIQ MLUTS voiding and incontinence scores of 5/20 [2-6] and 1/24 [1-3], respectively. Women had median [IQR] ICIQ FLUTS voiding and incontinence scores of 1/12 [1-3] and 5/20 [3-8], respectively; higher is worse. Fifty-nine (55%) patients reported being sexually active in the last month. Men had a median [IQR] IIEF score of 14/25 [6-19]; higher is better. Only age (OR 1.17; P = 0.04) was significantly associated with IIEF ≤ 11 (moderate or severe ED). Women had a median [IQR] FSFI score of 20.2/26 [13.6-24.9]; higher is better. Age < 65 was associated with sexual dysfunction, defined as FSFI < 26.55 (OR, 5.5; P = 0.04). Forty (37%) patients disagreed or strongly disagreed that they were prepared for long-term side effects. Seventy (65%) patients agreed or strongly agreed that educational materials would have been helpful. CONCLUSION SCCA survivors experience significant long-term bowel and sexual toxicities from modern CRT. Larger tumors and higher RT doses may be associated with worse function. Interventions to reduce toxicities and improve patient education are needed.

PURPOSE:High-quality cancer care must incorporate patients' personal values in decision making throughout illness. Unfortunately, patient values are neither consistently elicited nor easily accessible in the electronic health record (EHR). Memorial Sloan Kettering Cancer Center is deploying a major EHR innovation, called the Patient Values Tab, which provides ready access to patients' values and personhood. To inform the Tab's design, we interviewed a large, diverse group of institutional stakeholders to understand their user needs for this Tab.METHODS:Qualitative data were collected through semistructured, audio-recorded, in-person, individual interviews. An interdisciplinary team of four coders conducted a process of thematic content analysis. Thematic saturation was achieved, and member checking was performed.RESULTS:A total of 110 stakeholders were approached and interviewed. Participants comprised a wide range of disciplines or professions and others involved in hospital and/or clinic administration. Analysis revealed the following themes related to important Tab content: personhood, support system or resources, social history, communication preferences, future planning, end of life, and illness and treatment understanding. Participants also discussed implementation considerations, the Tab's potential to improve communication, and privacy implications.CONCLUSION:This study focused on a major EHR innovation to centralize information about values and personhood of patients with cancer. We elicited views of over 100 institutional stakeholders through in-depth interviews that were rigorously analyzed, yielding themes related to content and format that helped guide the Tab's design. The interviews generated a sense of ownership and enthusiasm for the Tab among future users. The Tab's introduction advances the use of the EHR as a driver of the delivery of patient-centered care.

Purpose/Objective(s) Radiation therapy (RT) has been shown to prolong survival for patients with select oligometastatic cancers. Limited long-term follow-up data exist to determine if the prolonged survival correlates with cure versus a delayed relapse. To investigate this, we evaluated the clinical and disease characteristics of long-term survivors treated with definitive RT for oligometastatic gynecological cancer at our institution. Materials/Methods We performed a landmark analysis in patients with oligometastatic gynecological cancer (OMGC) who survived for at least 5 years following treatment of their metastasis. OMGC was defined as metastasis (maximum of 5 total and 3 per site) present at a distant site at time of diagnosis or at a regional or distant site at time of recurrence. All patients received definitive RT between 2000 and 2015. Demographic and clinical variables were extracted from the medical record. Disease-free survival (DFS) after treatment of the first ROMGC was modeled using Kaplan Meier curves. Results 48 patients with OMGC were analyzed; 20 (41.7%) had ovarian cancer, 16 (33.3%) had uterine cancer, 11 (22.9%) had cervical cancer, 1 (2.1%) had vaginal cancer. Median age was 52 years. A majority (45.8%) were stage III at primary diagnosis. The most common histology was adenocarcinoma (35.4%). The most common site of OMGC was in the pelvic lymph nodes (LN) (40.7%), with the following other sites: para-aortic LN (38.9%), supraclavicular LN (7.4%), lung (5.6%), mediastinal LN (3.7%), and axillary LN (3.7%). The median size was 2 cm. The median [interquartile range (IQR)] total RT dose and fractionation was 62.1 [52.5-64.5] Gy and 2.1 [2-2.2] Gy/fraction. The majority (70.8%) were treated with intensity-modulated RT. 25 (52.1%) patients received concurrent chemoRT (CRT) for their OMGC. After a median follow-up of 9.9 years after OMGC treatment, median [range] DFS for all patients was 73 [4-212] months (mo). 5-year DFS for cervical, uterine, and ovarian cancers was 82% (95% confidence interval [CI], 45-95%), 69% (CI, 41-86%), and 35% (CI, 16-55%), respectively. Patients who received CRT had better median DFS than those treated with RT alone (103 vs. 65 mo, P = 0.18). Patients with nodal OMGC had similar median DFS as those with non-nodal OMGC (73 vs. 66 mo, P = 0.86). During the first OMGC course, patients treated for 1 site had worse median DFS than those treated for 2+ sites (65 vs. 103 mo, P = 0.61). Of all 48 patients, 8 (16.7%) died of gynecologic cancer, 11 (22.9%) died of other causes, 3 (6.3%) had progression of disease. The remaining 26 (54.2%) patients were disease free at long-term follow up. Conclusion Cure is possible for patients treated definitively for OMGC. Patients with cervical cancer, a greater number of treated OMGC sites, and treated with CRT had the longest DFS among this selected cohort. A randomized trial in oligometastatic gynecologic cancer is needed to determine if RT increases overall survival. Author Disclosure K.L. Corrigan: None. A.K. Yoder: None. L.L. Lin: Employee; VA Hospital. Research Grant; Astra Zeneca. Travel Expenses; Astra Zeneca. A. Jhingran; American Board of Radiology. M.M. Joyner: Consultation with executive management and participation in board meetings; Frontline Bioenergy. P.J. Eifel: Travel Expenses; National Cancer Center Network. Stock; Apple Computer. L. Colbert: None. K.H. Lu: None. A.H. Klopp: Research Grant; MD Anderson Cancer Center SPORE Grant.

HIV treatment is complex and has changed since the early years of the epidemic, especially as relates to treatment options for patients with cancer. This article focuses on disparities in cancer treatment care for people living with HIV.

Background. Anaplastic thyroid cancer (ATC) is rare, accounting for 1-2% of thyroid malignancies. Median survival is only 3-10 months, and the optimal therapeutic approach has not been established. This study aimed to evaluate outcomes in ATC based on treatment modality. Methods. Retrospective review was performed for patients treated at a single institution between 1990 and 2015. Demographic and clinical covariates were extracted from the medical record. Overall survival (OS) was modeled using Kaplan Meier curves for different treatment modalities. Univariate and multivariate analyses were conducted to assess the relationships between treatment and disease characteristics and OS. Results. 28 patients with ATC were identified (n = 16 female, n = 12 male; n = 22 Caucasian, n = 6 African-American; median age 70.9). Majority presented as Stage IVB (71.4%). Most patients received multimodality therapy. 19 patients underwent local surgical resection. 21 patients received locoregional external beam radiotherapy (EBRT) with a median cumulative dose of 3,000 cGy and median number of fractions of 16. 14 patients received systemic therapy (n = 11 concurrent with EBRT), most commonly doxorubicin (n = 9). 16 patients were never disease free, 11 patients had disease recurrence, and 1 patient had no evidence of disease progression. Median OS was 4 months with 1-year survival of 17.9%. Regression analysis showed that EBRT (HR: 0.174; 95% CI: 0.050–0.613; p=0.007) and surgical resection (HR: 0.198; 95% CI: 0.065–0.598; p=0.004) were associated with improved OS. Administration of chemotherapy was not associated with OS. Conclusions. Anaplastic thyroid cancer patients receiving EBRT to the thyroid area/neck and/or surgical resection had better OS than patients without these therapies, though selection bias likely contributed to improved outcomes since patients who can undergo these therapies tend to have better performance status. Prognosis remains poor overall, and new therapeutic approaches are needed to improve outcomes.

Background: With improved antiretroviral therapy, people living with HIV are aging and non-AIDS-defining cancers have increasing prevalence in this population. Yet, population-based studies demonstrate that people with HIV are less likely to receive cancer treatment, which contributes to lower cancer-specific survival. Past studies have examined cancer disparities at the provider and healthy system levels, but have not explored the drivers of cancer treatment disparities from the patient’s perspective. We aimed to investigate barriers and facilitators of cancer treatment among patients living with HIV, along with perceptions of their cancer diagnosis and treatment, to inform future interventions, reduce disparities, and improve outcomes. Methods: We conducted in-depth interviews with 27 HIV-infected cancer patients to examine perceptions and care engagement in this population. We recruited equal numbers of patients who had (a) past cancer treatment, (b) were currently undergoing cancer treatment, or (c) experienced challenges with receiving or completing cancer treatment. Semi-structured interviews explored multiple topics related to HIV and cancer care, including treatment decision-making, patient-provider interactions, stigma, coping, and barriers to care. Patients were recruited until thematic saturation was reached. Results: Study participants were predominantly male (n=22, 81%) with a median age of 56 years and median annual household income of $24,000. Prevailing themes from the interviews included descriptions of the “devastating” impact of a cancer diagnosis, with a considerable dual burden of pre-existing HIV. Participants noted that having HIV added anxiety about cancer treatment, side effects, and potential treatment interactions. Among those who experienced cancer treatment adherence challenges, barriers included cancer treatment side effects, stigma, transportation difficulties, cost of care, and challenges with coping and mental health. Despite these challenges, participants generally reported having positive healthcare experiences, including compassionate providers, ease of referral, and sound communication. Several participants indicated that their past experiences of coping with HIV had prepared them to accept and address their cancer diagnosis. Conclusions: This is the first qualitative study assessing barriers and facilitators to cancer care among people living with HIV and cancer in the U.S. For many HIV-infected patients, a cancer diagnosis creates substantial added stress to an already challenging social and medical situation. Often, these stressors impact patients’ ability to complete cancer treatment. Resiliency was noted to be a key facilitator, with participants frequently citing family, friends, faith, and the healthcare system as key sources of support. Citation Format: Kelsey L Corrigan, Brandon A Knettel, Noelani Ho, Stuart Carr, Bijal Shah, Joan Cahill, Melissa Watt, Gita Suneja. Cancer care in people with HIV: Identifying adherence challenges to improve outcomes [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr A043.

Background: Funding for neglected disease product development fell from 2009-2015, other than a brief injection of Ebola funding. One impediment to mobilizing resources is a lack of information on product candidates, the estimated costs to move them through the pipeline, and the likelihood of specific launches. This study aimed to help fill these information gaps. Methods: We conducted a pipeline portfolio review to identify current candidates for 35 neglected diseases. Using an adapted version of the Portfolio to Impact financial modelling tool, we estimated the costs to move these candidates through the pipeline over the next decade and the likely launches. Since the current pipeline is unlikely to yield several critical products, we estimated the costs to develop a set of priority “missing” products. Results: We found 685 neglected disease product candidates as of August 31, 2017; 538 candidates met inclusion criteria for input into the model. It would cost about $16.3 billion (range $13.4-19.8B) to move these candidates through the pipeline, with three-quarters of the costs incurred in the first 5 years, resulting in about 128 (89-160) expected product launches. Based on the current pipeline, there would be few launches of complex new chemical entities; launches of highly efficacious HIV, tuberculosis, or malaria vaccines would be unlikely. Estimated additional costs to launch one of each of 18 key missing products are $13.6B assuming lowest product complexity or $21.8B assuming highest complexity ($8.1B-36.6B). Over the next 5 years, total estimated costs to move current candidates through the pipeline and develop these 18 missing products would be around $4.5B (low complexity missing products) or $5.8B/year (high complexity missing products). Conclusions: Since current annual global spending on product development is about $3B, this study suggests the annual funding gap over the next 5 years is at least $1.5-2.8B.

Choosing Wisely is a comprehensive set of recommendations that guides clinicians and patients away from low-value services. The recommendations were reviewed to investigate their breadth and limitations. The authors performed an abstraction of all Choosing Wisely recommendations between March 1 and May 27, 2016. Descriptive statistics were used to characterize various topics found in the recommendations. Of the 461 Choosing Wisely recommendations, 48% targeted workup studies, 26% non–medication management, 20% medication management, and 6% disease prevention. The most commonly targeted medical issues were coronary artery disease (9%), antibiotics overuse (8%), back pain (6%), breast cancer (5%), and prostate cancer (4%). A limited focus was found on disease prevention and a lack of alignment with health care quality measures. Characterization of Choosing Wisely revealed a comprehensive set of recommendations that addresses low-value care across many specialties. Ultimately, this study provides guidance for promoting the creation and implementation of more patient-centered, representative recommendations.