Associations between geography, decision-making style, and interest in cancer clinical trial participation.

BACKGROUND: Clinical trials offer novel treatments, which are essential to high quality cancer care. Patients living in rural areas are often underrepresented in clinical trials due to several factors. This study evaluated the association between rurality and interest in clinical trial participation, change in interest, and treatment decision-making style preference. METHODS: This cohort study included patients with cancer receiving oncology care at the University of Alabama at Birmingham from 2017 to 2019. Associations between treatment decision-making preference and the interaction between rurality and area deprivation were analyzed using multinomial logistic regression. Initial interest in clinical trial participation and change in interest were analyzed using modified Poisson regressions with robust standard errors. Initial interest model was stratified by Area Deprivation Index (ADI; higher vs. lower disadvantaged). RESULTS: In adjusted models, patients in rural versus urban areas had similar initial interest in clinical trials, both those in higher (40% vs. 50%) and lower disadvantaged settings (54% vs. 62%). Additionally, rural versus urban patients had similar change of clinical trial interest for both those who changed from uninterested-to-interested (31% vs. 26%) and interested-to-uninterested (47% vs. 42%). CONCLUSION: This study compares the interest in clinical trial participation among patients living in rural and urban settings. Lack of interest may be secondary to barriers that patients in rural areas face (e.g., transportation, financial, access). Most rural patients prefer a shared treatment decision-making style, which should be considered when identifying interventions to increase enrollment of underserved rural patients in clinical trials.

Neoadjuvant atezolizumab in combination with sequential nab-paclitaxel and anthracycline-based chemotherapy versus placebo and chemotherapy in patients with early-stage triple-negative breast cancer (IMpassion031): a randomised, double-blind, phase 3 trial.

BACKGROUND: Preferred neoadjuvant regimens for early-stage triple-negative breast cancer (TNBC) include anthracycline-cyclophosphamide and taxane-based chemotherapy. IMpassion031 compared efficacy and safety of atezolizumab versus placebo combined with nab-paclitaxel followed by doxorubicin plus cyclophosphamide as neoadjuvant treatment for early-stage TNBC. METHODS: This double-blind, randomised, phase 3 study enrolled patients in 75 academic and community sites in 13 countries. Patients aged 18 years or older with previously untreated stage II-III histologically documented TNBC were randomly assigned (1:1) to receive chemotherapy plus intravenous atezolizumab at 840 mg or placebo every 2 weeks. Chemotherapy comprised of nab-paclitaxel at 125 mg/m2 every week for 12 weeks followed by doxorubicin at 60 mg/m2 and cyclophosphamide at 600 mg/m2 every 2 weeks for 8 weeks, which was then followed by surgery. Stratification was by clinical breast cancer stage and programmed cell death ligand 1 (PD-L1) status. Co-primary endpoints were pathological complete response in all-randomised (ie, all randomly assigned patients in the intention-to-treat population) and PD-L1-positive (ie, patients with PD-L1-expressing tumour infiltrating immune cells covering ≥1% of tumour area) populations. This study is registered with ClinicalTrials.gov (NCT03197935), Eudra (CT2016-004734-22), and the Japan Pharmaceutical Information Center (JapicCTI-173630), and is ongoing. FINDINGS: Between July 7, 2017, and Sept 24, 2019, 455 patients were recruited and assessed for eligibility. Of the 333 eligible patients, 165 were randomly assigned to receive atezolizumab plus chemotherapy and 168 to placebo plus chemotherapy. At data cutoff (April 3, 2020), median follow-up was 20·6 months (IQR 8·7-24·9) in the atezolizumab plus chemotherapy group and 19·8 months (8·1-24·5) in the placebo plus chemotherapy group. Pathological complete response was documented in 95 (58%, 95% CI 50-65) patients in the atezolizumab plus chemotherapy group and 69 (41%, 34-49) patients in the placebo plus chemotherapy group (rate difference 17%, 95% CI 6-27; one-sided p=0·0044 [significance boundary 0·0184]). In the PD-L1-positive population, pathological complete response was documented in 53 (69%, 95% CI 57-79) of 77 patients in the atezolizumab plus chemotherapy group versus 37 (49%, 38-61) of 75 patients in the placebo plus chemotherapy group (rate difference 20%, 95% CI 4-35; one-sided p=0·021 [significance boundary 0·0184]). In the neoadjuvant phase, grade 3-4 adverse events were balanced and treatment-related serious adverse events occurred in 37 (23%) and 26 (16%) patients, with one patient per group experiencing an unrelated grade 5 adverse event (traffic accident in the atezolizumab plus chemotherapy group and pneumonia in the placebo plus chemotherapy group). INTERPRETATION: In patients with early-stage TNBC, neoadjuvant treatment with atezolizumab in combination with nab-paclitaxel and anthracycline-based chemotherapy significantly improved pathological complete response rates with an acceptable safety profile. FUNDING: F Hoffmann-La Roche/Genentech.

Long term follow-up of neoadjuvant chemotherapy for non-small cell lung cancer (NSCLC) investigating early positron emission tomography (PET) scan as a predictor of outcome.

BACKGROUND: Neoadjuvant chemotherapy is effective in improving survival of resectable NSCLC. Based on findings in the adjuvant and metastatic setting, FDG positron emission tomography (PET) scans may offer early prognostic or predictive value after one cycle of induction chemotherapy. METHODS: In this phase II non-randomized trial, patients with AJCC version 6 stage IB to IIIB operable NSCLC were treated with 3 cycles of cisplatin and pemetrexed neoadjuvant chemotherapy. Patients underwent FDG-PET scanning prior to and 18 to 21 days after the first cycle of chemotherapy. Investigators caring for patients were blinded to results, unless the scans showed evidence of disease progression. FDG-PET response was defined prospectively as a ≥ 20% decrease in the SUV of the primary lesion. RESULTS: Between October 2005 and February 2010, 25 patients enrolled. Fifty two percent were female, 88% white, and median age was 62 years. Histology was divided into adenocarcinoma 66%, not otherwise specified (NOS) 16%, squamous cell 12%, and large cell 4%. Stage distribution was: 16% IB, 4% IIB, and 79% IIIA. Treatment was well tolerated and only one patient had a grade 4 toxicity. The median follow up was 95 months. The 5 year progression free survival (PFS) and overall survival (OS) for the entire population were 54 and 67%, respectively. Eighteen patients had a baseline FDG-PET scan and a repeat scan at day 18-21 available for comparison. Ten patients (56%) were considered metabolic responders on the day 18-21 FDG-PET scan. Responders had a 5 year PFS and OS of 60 and 70%, respectively, while the percentage for non-responders was 63 and 75% (p = 0.96 and 0.85). CONCLUSIONS: This phase II trial did not demonstrate that a PET scan after one cycle of chemotherapy can predict survival outcomes of patients with NSCLC treated with neoadjuvant chemotherapy. TRIAL REGISTRATION: NCT00227539 registered September 28th, 2005.

Resource-stratified implementation of a community-based breast cancer management programme in Peru.

Breast cancer incidence and mortality rates continue to rise in Peru, with related deaths projected to increase from 1208 in 2012, to 2054 in 2030. Despite improvements in national cancer control plans, various barriers to positive breast cancer outcomes remain. Multiorganisational stakeholder collaboration is needed for the development of functional, sustainable early diagnosis, treatment and supportive care programmes with the potential to achieve measurable outcomes. In 2011, PATH, the Peruvian Ministry of Health, the National Cancer Institute in Lima, and the Regional Cancer Institute in Trujillo collaborated to establish the Community-based Program for Breast Health, the aim of which was to improve breast health-care delivery in Peru. A four-step, resource-stratified implementation strategy was used to establish an effective community-based triage programme and a practical early diagnosis scheme within existing multilevel health-care infrastructure. The phased implementation model was initially developed by the Breast Cancer Initiative 2·5: a group of health and non-governmental organisations who collaborate to improve breast cancer outcomes. To date, the Community-based Program for Breast Health has successfully implemented steps 1, 2, and 3 of the Breast Cancer Initiative 2·5 model in Peru, with reports of increased awareness of breast cancer among women, improved capacity for early diagnosis among health workers, and the creation of stronger and more functional linkages between the primary levels (ie, local or community) and higher levels (ie, district, region, and national) of health care. The Community-based Program for Breast Health is a successful example of stakeholder and collaborator involvement-both internal and external to Peru-in the design and implementation of resource-appropriate interventions to increase breast health-care capacity in a middle-income Latin American country.

Framework for radiation pneumonitis risk stratification based on anatomic and perfused lung dosimetry.

PURPOSE: To design and apply a framework for predicting symptomatic radiation pneumonitis in patients undergoing thoracic radiation, using both pretreatment anatomic and perfused lung dose-volume parameters. MATERIALS AND METHODS: Radiation treatment planning CT scans were coregistered with pretreatment [99mTc]MAA perfusion SPECT/CT scans of 20 patients who underwent definitive thoracic radiation. Clinical radiation pneumonitis was defined as grade ≥ 2 (CTCAE v4 grading system). Anatomic lung dose-volume parameters were collected from the treatment planning scans. Perfusion dose-volume parameters were calculated from pretreatment SPECT/CT scans. Equivalent doses in 2 Gy per fraction were calculated in the lung to account for differences in treatment regimens and spatial variations in lung dose (EQD2lung). RESULTS: Anatomic lung dosimetric parameters (MLD) and functional lung dosimetric parameters (pMLD70%) were identified as candidate predictors of grade ≥ 2 radiation pneumonitis (AUC > 0.93, p < 0.01). Pairing of an anatomic and functional dosimetric parameter (e. g., MLD and pMLD70%) may further improve prediction accuracy. Not all individuals with high anatomic lung dose (MLD > 13.6 GyEQD2lung, 19.3 Gy for patients receiving 60 Gy in 30 fractions) developed radiation pneumonitis, but all individuals who also had high mean dose to perfused lung (pMLD70% > 13.3 GyEQD2) developed radiation pneumonitis. CONCLUSIONS: The preliminary application of this framework revealed differences between anatomic and perfused lung dosimetry in this limited patient cohort. The addition of perfused lung parameters may help risk stratify patients for radiation pneumonitis, especially in treatment plans with high anatomic mean lung dose. Further investigations are warranted.

Cancer care in lesbian, gay, bisexual, transgender and queer populations.

Lesbian, gay, bisexual, transgender and queer (LGBTQ) populations experience health and healthcare disparities that may place them at higher risk for developing cancer. In addition, LGBTQ communities have psychosocial factors, such as fear of discrimination, that have substantial impacts on their medical care. As a result, these populations have specific needs with regard to cancer screening, treatment and support that must be addressed by cancer care providers. Although much has been done to address cancer care in the general population, more improvement is needed in the care of LGBTQ patients. We aim to present an overview of the current state of LGBTQ cancer care, opportunities for improvement and how cancer centers and providers can create a better future for the care of LGBTQ cancer patients.

Treatment of early-stage prostate cancer among rural and urban patients.

BACKGROUND: Geographic barriers and limited availability of cancer specialists may influence early prostate cancer treatment options for rural men. This study compares receipt of different early prostate cancer treatments between rural and urban patients. METHODS: Using 2004-2006 SEER Limited-Use Data, 51,982 early prostate cancer patients were identified (T1c, T2a, T2b, T2c, T2NOS; no metastases) who were most likely to benefit from definitive treatment (< 75 years old, Gleason score < 8, PSA ≤ 20). Definitive treatment included radical prostatectomy, daily external beam radiation for 5 to 8 weeks, brachytherapy, or combination external beam radiation/brachytherapy. Adjusted definitive treatment rates were calculated by rural-urban residence overall, and for different sociodemographic and cancer characteristics, and different states based on logistic regression analyses, using general estimating equation methods to account for clustering by county. RESULTS: Adjusted definitive treatment rates were lower for rural (83.7%) than urban (87.1%) patients with early-stage prostate cancer (P ≤ .01). Rural men were more likely than urban men to receive non-definitive surgical treatment and no initial treatment. The lowest definitive treatment rates were among rural subgroups: 70 to 74 years (73.9%), African Americans (75.6%), American Indians/Alaska Natives (77.8%), single/separated/divorced (76.8%), living in New Mexico (69.3%), and living in counties with persistent poverty (79.6%). CONCLUSIONS: Between 2004 and 2006, this adjusted analysis found that men who were living in rural areas were less likely to receive definitive treatment for their early-stage prostate cancer than those living in urban areas. Certain rural patient groups with prostate cancer need particular attention to ensure their access to appropriate treatment. Rural providers, rural health care systems, and cancer advocacy and support organizations should ensure resources are in place so that the most vulnerable rural groups (men between 60 and 74 years of age; African American men; men who are single, separated, or divorced; and men living in rural New Mexico) can make informed prostate cancer treatment choices based on their preferences.

Considerations for Embedding Inclusive Research Principles in the Design and Execution of Clinical Trials.

There is a growing recognition that the clinical research enterprise has a diversity problem, given that many clinical trials recruit historically marginalized individuals or patients reflective of real-world data at a rate that is far below the incidence and prevalence of the disease for which the investigational therapy or device is targeting. This lack of diversity in clinical research participation can obscure the safety and efficacy of drug therapies and limits our collective ability to develop effective treatments for all patients, leading to even wider health disparities. This review article provides an in-depth analysis of the impact of this bias on public health, along with a description of some of the barriers that prevent historically marginalized populations from participating in clinical research. Some practical solutions that can be employed to increase diversity in clinical trial participation are also discussed, including the crucial role clinical trial sponsors, research organizations, patients, and caregivers need to play in supporting the industry to achieve this ambitious but necessary goal.

Promoting Women and Historically Excluded Minorities in Medicine as Essential Leaders of Research.

Women and historically excluded minorities are underrepresented in clinical research. At the ASTRO 2021 annual meeting, the authors reviewed several strategies to improve on this issue. Implementation of such strategies should not only improve their visibility but also provide increased opportunities for their advancement and work in clinical research.

Receipt of recommended radiation therapy among rural and urban cancer patients.

BACKGROUND: Rural populations have limited geographic access to radiation therapy. The current study examines whether rural patients with cancer are less likely than urban patients with cancer to receive recommended radiation therapy, and identifies factors influencing rural versus urban differences in radiation therapy receipt. METHODS: The current study included 14,692 rural and 107,834 urban patients with 5 cancer types and stages for which radiation therapy was recommended. The authors used 2000 to 2004 Surveillance, Epidemiology, and End Results (SEER) Limited-Use Data from 8 state-based (California, Connecticut, Hawaii, Iowa, Kentucky, Louisiana, New Mexico, and Utah) and 3 county-based (Atlanta, rural Georgia, and Seattle/Puget Sound) cancer registries. Adjusted radiation therapy receipt rates were calculated by rural versus urban residence overall, for different sociodemographic and cancer characteristics, and for different states based on logistic regression analyses using general estimating equation methods to account for patient clustering by county. RESULTS: Adjusted rates of radiation therapy receipt were lower for rural (62.1%) than urban (69.1%) patients with breast cancer (P ≤ .001). Among patients with breast cancer, radiation therapy receipt differed more by sociodemographic characteristics (eg, rural patients aged < 50 years had a 67.1% receipt rate, whereas those aged ≥ 80 years had a radiation therapy receipt rate of 29.1%) than rural versus urban residence. Adjusted rates of radiation therapy receipt were similar for rural and urban patients with other cancer types overall (66.1% vs 68.2%; difference not significant), although there were differences between urban and rural patients with regard to radiation therapy receipt for patients with stage IIIA nonsmall cell lung cancer (66.2% vs 60.7%; P ≤ .01). CONCLUSIONS: Sociodemographics, cancer types and stages, and state of residence appear to have a greater influence over receipt of radiation therapy than rural versus urban residence location, suggesting that factors such as social support, receipt of other cancer treatments, and regional practice patterns are important determinants of radiation therapy receipt.

Ineligible, Unaware, or Uninterested? Associations Between Underrepresented Patient Populations and Retention in the Pathway to Cancer Clinical Trial Enrollment.

PURPOSE: Cancer clinical trials can benefit current and future patients; however, Black patients, rural residents, and patients living in disadvantaged areas are often underrepresented. Using an adapted version of Unger and colleagues' model of the process of clinical trial enrollment, we evaluated the relationship between underrepresented patient populations and trial end points. METHODS: This retrospective study included 512 patients with breast or ovarian cancer who were prescribed a therapeutic drug at the University of Alabama at Birmingham from January 2017 to February 2020. Patient eligibility was assessed using open clinical trials. We estimated odds ratios and 95% CIs using logistic regression models to examine the relationship between underrepresented patient populations and trial enrollment end points: eligibility, interest, offer, enrollment, and declining enrollment. RESULTS: Of the patients in our sample, 27% were Black, 18% were rural residents, and 19% lived in higher disadvantaged neighborhoods. In adjusted models, each comparison group had similar odds of being eligible for a clinical trial. Black versus White patients had 0.40 times the odds of interest in clinical trials and 0.56 times the odds of enrollment. Patients living in areas of higher versus lower disadvantage had 0.46 times the odds of enrolling and 3.40 times the odds of declining enrollment when offered. CONCLUSION: Eligibility did not drive clinical trial enrollment disparities in our sample; however, retention in the clinical trial enrollment process appears to vary by group. Additional work is needed to understand how interventions can be tailored to each population's specific needs.

Patient-reported outcomes from a randomized trial of neoadjuvant atezolizumab-chemotherapy in early triple-negative breast cancer.

Patient-reported outcomes data assessing patients' experience of immunotherapy treatment burden in potentially curable early-stage triple-negative breast cancer (TNBC) are lacking. These patient-reported data inform clinical benefit and decision-making for adding atezolizumab to neoadjuvant chemotherapy in early-stage TNBC. IMpassion031 (NCT03197935) randomly assigned patients with stage II/III TNBC (T2-T4d primary tumors) to 5 cycles (4 weeks/cycle) of every 2-week neoadjuvant atezolizumab 840 mg or placebo with weekly nab-paclitaxel (3 cycles) followed by every 2-week dose-dense doxorubicin+cyclophosphamide (2 cycles). After surgery, the atezolizumab-chemotherapy arm received atezolizumab 1200 mg every 3 weeks (11 cycles). The placebo-chemotherapy arm was observed under standard of care. To assess treatment burden from the patients' perspective, which comprised measures of the treatment-related impact on patients' functioning and health-related quality of life (HRQoL), as well as patients' experience of treatment-related symptoms plus their associated bother, patients completed the EORTC QLQ-C30 and FACT-G single-item GP5. Predefined secondary endpoints included mean and mean change from baseline values in the QLQ-C30 function (role and physical) and global health status/quality of life scales. Exploratory endpoints included mean and mean change from baseline in treatment-related symptoms, and treatment side effect bother. Mean physical, role function, and HRQoL were similar between arms at baseline and throughout treatment. In the neoadjuvant period, both arms exhibited clinically meaningful declines of similar magnitude from baseline in physical, role function, and HRQoL, and reported similar treatment side effect to bother at each visit. Improved pathologic complete response from adding atezolizumab to neoadjuvant chemotherapy for early-stage TNBC occurred without imposing additional treatment burden on patients.

The International Core Literature Consensus (ICLC): an alternative curriculum for Oncologists.

Oncologists must familiarize themselves with a complex evidence base. Several curricula have been devised, but it is not clear how these are used. We chose breast cancer, since this has a large literature base. Of the 285 radiation and medical oncology trainees in the USA and UK responding to our survey, over 90% reported knowledge of the literature was essential. Just over half of respondents had actually read the ASCO or ESMO curricula, with only 23% reporting that the curricula were important in their learning. Our survey revealed dissatisfaction with current curricula and a demand for more pragmatic literature guidance. We designed an alternative curriculum by using a 21-member peer review group to validate a list of key papers in breast oncology. Oncologists in training need guidance to direct their study. A curriculum based on an International Core Literature Consensus might match the needs of trainees more closely.

A Novel Curriculum for Medical Student Training in LGBTQ Healthcare: A Regional Pathway Experience.

BACKGROUND: Lesbian, gay, bisexual, transgender, and queer (LGBTQ) individuals face considerable health disparities, often due to a lack of LGBTQ-competent care. Such disparities and lack of access to informed care are even more staggering in rural settings. As the state medical school for the Washington, Wyoming, Alaska, Montana, and Idaho (WWAMI) region, the University of Washington School of Medicine (UWSOM) is in a unique position to train future physicians to provide healthcare that meets the needs of LGBTQ patients both regionally and nationally. OBJECTIVE: To describe our methodology of developing a student-driven longitudinal, region-wide curriculum to train medical students to provide high-quality care to LGBTQ patients. METHODS: A 4-year LGBTQ Health Pathway was developed and implemented as a student-led initiative at the UWSOM. First- and second-year medical students at sites across the WWAMI region are eligible to apply. Accepted Pathway students complete a diverse set of pre-clinical and clinical components: online modules, didactic courses, longitudinal community service/advocacy work, a scholarly project, and a novel clinical clerkship in LGBTQ health developed specifically for this Pathway experience. Students who complete all requirements receive a certification of Pathway completion. This is incorporated into the Medical Student Performance Evaluation as part of residency applications. RESULTS: The LGBTQ Health Pathway is currently in its fourth year. A total of 43 total students have enrolled, of whom 37.3% are based in the WWAMI region outside of Seattle. Pathway students have completed a variety of scholarly projects on LGBTQ topics, and over 1000 hours of community service/advocacy. The first cohort of 8 students graduated with a certificate of Pathway completion in spring 2020. CONCLUSIONS: The LGBTQ Health Pathway at UWSOM is a novel education program for motivated medical students across the 5-state WWAMI region. The diverse milestones, longitudinal nature of the program, focus on rural communities, and opportunities for student leadership are all strengths and unique aspects of this program. The Pathway curriculum and methodology described here serve as a model for student involvement and leadership in medical education. This program enables medical students to enhance their training in the care of LGBTQ patients and provides a unique educational opportunity for future physicians who strive to better serve LGBTQ populations.

Intensity modulated radiation therapy following lumpectomy in early-stage breast cancer: Patterns of use and cost consequences among Medicare beneficiaries.

PURPOSE: In 2013, the American Society for Radiation Oncology (ASTRO) issued a Choosing Wisely recommendation against the routine use of intensity modulated radiotherapy (IMRT) for whole breast irradiation. We evaluated IMRT use and subsequent impact on Medicare expenditure in the period immediately preceding this recommendation to provide a baseline measure of IMRT use and associated cost consequences. METHODS AND MATERIALS: SEER records for women ≥66 years with first primary diagnosis of Stage I/II breast cancer (2008-2011) were linked with Medicare claims (2007-2012). Eligibility criteria included lumpectomy within 6 months of diagnosis and radiotherapy within 6 months of lumpectomy. We evaluated IMRT versus conventional radiotherapy (cRT) use overall and by SEER registry (12 sites). We used generalized estimating equations logit models to explore adjusted odds ratios (OR) for associations between clinical, sociodemographic, and health services characteristics and IMRT use. Mean costs were calculated from Medicare allowable costs in the year after diagnosis. RESULTS: Among 13,037 women, mean age was 74.4, 50.5% had left-sided breast cancer, and 19.8% received IMRT. IMRT use varied from 0% to 52% across SEER registries. In multivariable analysis, left-sided breast cancer (OR 1.75), living in a big metropolitan area (OR 2.39), living in a census tract with ≤$90,000 median income (OR 1.75), neutral or favorable local coverage determination (OR 3.86, 1.72, respectively), and free-standing treatment facility (OR 3.49) were associated with receipt of IMRT (p<0.001). Mean expenditure in the year after diagnosis was $8,499 greater (p<0.001) among women receiving IMRT versus cRT. CONCLUSION: We found highly variable use of IMRT and higher expenditure in the year after diagnosis among women treated with IMRT (vs. cRT) with early-stage breast cancer and Medicare insurance. Our findings suggest a considerable opportunity to reduce treatment variation and cost of care while improving alignment between practice and clinical guidelines.

Treatment of locally advanced adenoid cystic carcinoma of the trachea with neutron radiotherapy.

PURPOSE: To examine the efficacy of fast neutron radiotherapy in the treatment of locally advanced adenoid cystic carcinoma (ACC) of the trachea and to compare outcomes with and without high-dose-rate (HDR) endobronchial brachytherapy boost. METHODS AND MATERIALS: Between 1989 and 2005, a total of 20 patients with ACC of the trachea were treated with fast neutron radiotherapy at the University of Washington. Of these 20 patients, 19 were treated with curative intent. Neutron doses ranged from 10.7 to 19.95 Gy (median, 19.2 Gy). Six of these patients received an endobronchial brachytherapy boost using an HDR (192)Ir source (3.5 Gy x 2 fractions). Median duration of follow-up was 46 months (range, 10-121 months). RESULTS: The 5-year actuarial overall survival rate and median overall survival for the entire cohort were 89.4%, and 97 months, respectively. Overall survival was not statistically different among those patients receiving an endobronchial boost compared with those receiving neutron radiotherapy alone (100% vs. 68%, p = 0.36). The 5-year actuarial locoregional control rate for the entire cohort was 54.1%. The locoregional control rate was not statistically different among patients who received an endobronchial boost compared with those who received neutron radiotherapy alone (40% vs. 58%, p = 0.94). There were no cases of Grade > or =3 acute toxicity. There were 2 cases of Grade 3/4 chronic toxicity. CONCLUSIONS: Fast neutron radiotherapy is an effective treatment for locally advanced adenoid cystic carcinoma of the trachea, with acceptable treatment-related toxicity.

Dosimetric effects of the prone and supine positions on image guided localized prostate cancer radiotherapy.

PURPOSE: To compare target coverage and doses to rectum and bladder in IMRT of localized prostate cancer in the supine versus prone position, with the inclusion of image guidance. MATERIALS AND METHODS: Twenty patients with early stage localized prostate carcinoma who received external beam radiotherapy in the supine and prone positions underwent approximately 10 serial CT examinations in their respective treatment position in non-consecutive days, except for one patient who was treated prone but serially imaged supine. The prostate, bladder and rectum were contoured on all CT scans. A PTV was generated on the first scan of each patient's CT series by expanding the prostate with a 5mm margin and an IMRT plan was created. The resultant IMRT plan was then applied to that patient's remaining serial CT scans by aligning the initial CT image set with the subsequent serial CT image sets using (1) skin marks, (2) bony anatomy and (3) center of mass of the prostate. The dosimetric results from these three alignments were compared between the supine and prone groups. To account for the uncertainties associated with prostate delineation and intra-fractional geometric changes, a fictional "daily PTV" was generated by expanding the prostate with a 3mm margin on each serial CT scan. Thus, a more realistic target coverage index, V95, was quantified as the fraction of the daily PTV receiving at least 95% of the prescription dose. Dose-volume measures of the organs at risk were also compared. The fraction of the daily PTV contained by the initial PTV after each alignment method was quantified on each patient's serial CT scan, and is defined as PTV overlap index. RESULTS: As expected, alignment based on skin marks yielded unacceptable dose coverage for both groups of patients. Under bony alignment, the target coverage index, V95, was 97.3% and 93.6% for prone and supine patients (p<0.0001), respectively. The mean PTV overlap indices were 90.7% and 84.7% for prone and supine patients (p<0.0002), respectively. In the supine position 36% of cases showed a V95<95% after bony alignment, while only 12.5% of prone patients with V95<95% following bony alignment. Under soft-tissue alignment matching the center of mass of the prostate, the mean V95 was 99.3% and 98.6% (p<0.03) and the PTV overlap index was 97.7% and 94.8% (p<0.0002) for prone and supine groups, respectively. CONCLUSIONS: Soft-tissue alignment combined with 5mm planning margins is appropriate in minimizing treatment planning and delivery uncertainties in both the supine and prone positions. Alignment based on bony structures showed improved results over the use of skin marks for both supine and prone setups. Under bony alignment, the dose coverage and PTV overlap index for prone setup were statistically better than for supine setup, illustrating a more consistent geometric relationship between the prostate and the pelvic bony structures when patients were treated in the prone position.

Definitive chemoradiotherapy for non-small cell lung cancer with N2 disease.

The treatment of NSCLC continues to evolve over time. Newer therapies and techniques help achieve success in this difficult disease. Since the 1970s, one can observe trends in median survival and notice that they have improved from 9 to 10 months to now 15 to 24 months with concurrent chemoradiation. Unfortunately, despite the advances made, most patients still die from their disease. Chemoradiation without induction or consolidation therapy continues to remain the standard of care in this country for unresectable locally advanced NSCLC. Evaluation of epidermal growth factor receptor tyrosine kinase inhibitors and other biologics continue to be investigated but are not considered standard of care yet. Technologies continue to expand including the use of four-dimensional CT scans and PET scans to more accurately plan patients. Future application of molecular profiling to predict patients most likely to benefit from tailored chemotherapeutic approaches is awaited following validation in early- and advanced-stage disease. With continued diligence to testing new ideas in NSCLC, it is hoped that outcomes will continue to improve the lives of patients with this devastating disease.

Heart Dose and Outcomes in Radiation Treatment for Esophageal Cancer.

Purpose Studies have shown that radiation dose to the heart may be associated with worse outcomes in patients receiving chemoradiation for lung cancer. As esophageal cancer radiation treatment can result in relatively high cardiac doses, we evaluated a single-institution database of patients treated for esophageal cancer for heart dose and outcomes. Methods We retrospectively reviewed 59 patients with stage IIA-IIIB esophageal cancer treated with neoadjuvant chemoradiation to 50.4 Gy followed by esophagectomy from 2007-2015. Patient demographics and outcome data, including pathological response, local recurrence, distant metastases, and overall survival, were obtained. Mean heart dose (MHD), heart V5, V40, and V50, were calculated. Differences in patient characteristics between the three radiation therapy modalities: three-dimensional (3D) conformal radiotherapy (3D-CRT), intensity modulated radiotherapy (IMRT), and proton beam radiation therapy (PBT) were tested using non-parametric Kruskal-Wallis (K-W) analysis of variance (ANOVA). Patient characteristics and heart dosimetric parameters were screened by univariate Cox regression for an association to overall survival, and univariate predictors (p < 0.05) were then selected as inputs into a multivariate Cox regression model using stepwise backward elimination. Kaplan-Meier risk-stratified survival curves were plotted for the best univariate or multivariate Cox model variables. An exploratory subgroup univariate Cox regression was conducted in each of the treatment modalities (proton, IMRT, 3D-CRT). Results The median follow-up was 20 months. The median overall survival was 73 months. Eleven patients (20%) experienced a complete pathologic response (pCR). Only two patients (4%) experienced a local recurrence. On univariate analysis, predictors of survival were age, prior radiation, pathologic response in involved lymph nodes, and tumor length post-treatment. On a multivariate analysis, only pathologic nodal response (yN) remained significant (p = 0.007). There was no relationship between any heart dosimetric variables analyzed and any clinical outcomes. Conclusions In this retrospective review, radiation dose to the heart was not associated with inferior treatment outcomes in patients receiving trimodality therapy for esophageal cancer.

Correlation of Functional Lung Heterogeneity and Dosimetry to Radiation Pneumonitis using Perfusion SPECT/CT and FDG PET/CT Imaging.

PURPOSE: To apply a previously designed framework for predicting radiation pneumonitis by using pretreatment lung function heterogeneity metrics, anatomic dosimetry, and functional lung dosimetry derived from 2 imaging modalities within the same cohort. METHODS AND MATERIALS: Treatment planning computed tomography (CT) scans were co-registered with pretreatment [99mTc] macro-aggregated albumin perfusion single-photon positron emission tomography (SPECT)/CT scans and [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT scans of 28 patients who underwent definitive thoracic radiation. Clinical radiation pneumonitis was defined as grade ≥2 (Common Terminology Criteria for Adverse Events, v. 4). Anatomic dosimetric parameters (mean lung dose [MLD], volume receiving ≥20 Gy [V20]) were collected from treatment planning scans. Baseline functional lung heterogeneity parameters and functional lung dose-volume parameters were calculated from pretreatment SPECT/CT and FDG PET/CT scans. Functional heterogeneity parameters calculated over the tumor-subtracted lung included skewness, kurtosis, and coefficient of variation from perfusion SPECT and FDG PET and the global lung parenchymal glycolysis and mean standardized uptake value from FDG PET. Functional dose-volume parameters calculated in regions of highly functional lung, defined on perfusion (p) or SUV (s) images, included mean lung dose (pMLD, sMLD) and V20 (pV20, sV20). Fraction of integral lung function receiving ≥20 Gy (pF20, sF20) was also calculated. Equivalent doses in 2 Gy per fraction (EQD2) were calculated to account for differences in treatment regimens and dose fractionation (EQD2Lung). RESULTS: Two anatomic dosimetric parameters (MLD, V20) and 4 functional dosimetric parameters (pMLD, pV20, pF20, sF20) were significant predictors of grade ≥2 pneumonitis (area under the curve >0.84; P < .05). Dose-independent functional lung heterogeneity metrics were not associated with pneumonitis incidence. At thresholds of 100% sensitivity and 65% to 91% specificity, corresponding to maximum prediction accuracy for pneumonitis, these parameters had the following cutoff values: MLD = 13.6 Gy EQD2Lung, V20 = 25%, pMLD = 13.2 Gy EQD2Lung, pV20 = 15%, pF20 = 17%, and sF20 = 25%. Significant parameters MLD, V20, pF20, and sF20 were not cross-correlated to significant parameters pMLD and pV20, indicating that they may offer independently predictive information (Spearman ρ < 0.7). CONCLUSIONS: We reported differences in anatomic and functional lung dosimetry between patients with and without pneumonitis in this limited patient cohort. Adding selected independent functional lung parameters may risk stratify patients for pneumonitis. Validation studies are ongoing in a prospective functional lung avoidance trial at our institution.