Impact of Maximum Point Dose Within the Planning Target Volume on Local Control of Nonsmall Cell Lung Cancer Treated With Stereotactic Body Radiotherapy.

BACKGROUND: No consensus exists on the maximum dose delivered to the planning target volume (PTV) in the delivery of stereotactic body radiotherapy (SBRT) for primary lung cancer. We investigated whether higher biologically effective doses (BED) within the PTV were associated with improved tumor control. METHODS: We reviewed patients with early-stage, node-negative nonsmall cell lung cancer who received curative-intent SBRT between 2005 and 2018. We calculated the maximum BED (maxBED) within the PTV for all patients, analyzing outcomes using the cumulative incidence method and Fine-Gray test statistics to assess prognostic impact. RESULTS: We analyzed 171 patients (median age, 70.2; range, 43 to 90 y) with 181 lung nodules. Median follow-up was 2.7 years (range, 0.1 to 12 y) for all patients and 4.2 years (range, 0.2 to 8.4 y) for living patients. Median maximum tumor diameter was 1.9 cm (range, 0.7 to 5.6 cm). Patients received a prescription of 48 or 50 Gy in 4 or 5 fractions, respectively, except for one who received 60 Gy in 5 fractions. Median maxBED was 120 Gy (range, 101 to 171 Gy). There was no difference in the 3-year local control (LC) rate among patients treated with a maxBED<120 Gy versus ≥120 Gy ( P =0.83). CONCLUSIONS: No significant differences in LC were observed between patients with early-stage nonsmall cell lung cancer treated with SBRT in 4 or 5 fractions with a maxBED≥120 Gy. However, a higher maxBED trended toward improved LC rates, suggesting a maxBED threshold greater than 120 Gy may be needed to improve LC rates.

Quality-adjusted survival in women with gynecologic malignancies receiving IMRT after surgery: A Ppatient Rreported Ooutcome study of NRG oncology's RTOG 1203.

INTRODUCTION: NRG/RTOG 1203 compared 3-D conformal radiotherapy (3D CRT) to intensity-modulated radiotherapy (IMRT) in patients with endometrial or cervical cancer requiring post-operative radiotherapy after hysterectomy. The purpose of this study was to report the first quality-adjusted survival analysis comparing the two treatments. METHODS: NRG/RTOG 1203 randomized patients having undergone hysterectomy to either 3DCRT or IMRT. Stratification factors included RT dose, chemotherapy, and disease site. The EQ-5D, both index and visual analog scale (VAS), were obtained at baseline, 5 weeks after the start of RT, 4-6 weeks post RT and 1 and 3-years post RT. EQ-5D index and VAS scores along with quality-adjusted survival (QAS) were compared between treatment arms using the t-test at a two-sided significance level of 0.05. RESULTS: NRG/RTOG 1203 enrolled 289 patients of which 236 consented to participate in the patient reported outcome (PRO) assessments. QAS was higher in women treated with IMRT, 1374 vs 1333 days (p = 0.5) compared to patients treated with 3DCRT, but this difference was not statistically different. Patients treated with IMRT had less of a decline in VAS score 5 weeks post RT, -5.04, compared to patients treated with 3DCRT, -7.48, although not statistically significant (p = 0.38). CONCLUSION: This is the first report of the use of the EQ-5D comparing two radiotherapy techniques in the treatment of gynecologic malignancies after surgery. While there were no significant differences in QAS and VAS scores between patients who received IMRT vs. 3DCRT, RTOG 1203 was not powered to show statistical differences in these secondary endpoints.

Corrigendum to "Challenges in the transition to independent radiation oncology practice and targeted interventions for improvement" [Tech. Innov. Patient Support Radiat. Oncol. 24 (2022) 113-117].

[This corrects the article DOI: 10.1016/j.tipsro.2022.09.002.].

Challenges in the transition to independent radiation oncology practice and targeted interventions for improvement.

Numerous radiation oncology residents and junior attendings have identified common weaknesses in residency training that hinder the transition from training to independent practice. Recurrent themes include not only general autonomy but also proficiency in technical skills, such as treatment plan review and image verification, and nontechnical skills, such as leadership, mentorship, and education. While multiple strategies to address these deficiencies have been investigated, many are not widely available or may be difficult to implement. We aim to summarize the frequently cited challenges in the transition to independent radiation oncology practice as well as the pertinent interventions that have been explored.

Intensity-Modulated Radiation Therapy Reduces Patient-Reported Chronic Toxicity Compared With Conventional Pelvic Radiation Therapy: Updated Results of a Phase III Trial.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned coprimary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The purpose of this update was to determine differences in patient-reported chronic toxicity and disease outcomes with intensity-modulated radiation therapy (IMRT) compared with conventional pelvic radiation. Patients with cervical and endometrial cancers who received postoperative pelvic radiation were randomly assigned to conventional radiation therapy (CRT) or IMRT. Toxicity and quality of life were assessed using Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events, Expanded Prostate Cancer Index Composite (EPIC) bowel and urinary domains, and Functional Assessment of Cancer Therapy-General. Between 2012 and 2015, 279 eligible patients were enrolled to the study with a median follow-up of 37.8 months. There were no differences in overall survival (P = .53), disease-free survival (P = .21), or locoregional failure (P = .81). One year after RT, patients in the CRT arm experienced more high-level diarrhea frequency (5.8% IMRT v 15.1% CRT, P = .042) and a greater number had to take antidiarrheal medication two or more times a day (1.2% IMRT v 8.6% CRT, P = .036). At 3 years, women in the CRT arm reported a decline in urinary function, whereas the IMRT arm continued to improve (mean change in EPIC urinary score = 0.5, standard deviation = 13.0, IMRT v -6.0, standard deviation = 14.3, CRT, P = .005). In conclusion, IMRT reduces patient-reported chronic GI and urinary toxicity with no difference in treatment efficacy at 3 years.

Quality and Safety Considerations in Stereotactic Radiosurgery and Stereotactic Body Radiation Therapy: An ASTRO Safety White Paper Update.

PURPOSE: This updated report on stereotactic radiosurgery (SRS) and stereotactic body radiation therapy (SBRT) is part of a series of consensus-based white papers previously published addressing patient safety. Since the first white papers were published, SRS and SBRT technology and procedures have progressed significantly such that these procedures are now more commonly used. The complexity and submillimeter accuracy, and delivery of a higher dose per fraction requires an emphasis on best practices for technical, dosimetric, and quality assurance. Therefore, quality and patient safety considerations for these techniques remain an important area of focus. METHOD: The American Society for Radiation Oncology convened a task force to assess the original SRS/SBRT white paper and update content where appropriate. Recommendations were created using a consensus-building methodology and task force members indicated their level of agreement based on a 5-point Likert scale, from "strongly agree" to "strongly disagree." A prespecified threshold of ≥75% of raters who select "strongly agree" or "agree" indicated consensus. SUMMARY: This white paper builds on the previous version and uses of other guidance documents to broadly address SRS and SBRT delivery, primarily focusing on processes related to quality and safety. SRS and SBRT require a team-based approach, staffed by appropriately trained and credentialed specialists as well as significant personnel resources, specialized technology, and implementation time. A thorough feasibility analysis of resources is required to achieve the clinical and technical goals and thoroughly discussed with all personnel before undertaking new disease sites. A comprehensive quality assurance program must be developed, using established treatment guidelines, to ensure SRS and SBRT are performed in a safe and effective manner. Patient safety in SRS/SBRT is everyone's responsibility and professional organizations, regulators, vendors, and end-users must demonstrate a clear commitment to working together to ensure the highest levels of safety.

How 3 Academic Centers Prescribe Stereotactic Body Radiation Therapy for Primary Lung Cancer.

Stereotactic body radiation therapy (SBRT) is commonly used to treat early-stage, node-negative primary lung cancer, but society guidelines provide limited information regarding several technical aspects of SBRT, leading to potential variation in practice. In this report, we present the technical details used by 3 academic institutions when treating a solitary primary lung tumor up to 5 cm in dimension with curative-intent SBRT. We provide specifications outlined in major active or recently completed clinical trials. Among the participating institutions, we discovered multiple divergences in treatment parameters, including, but not limited to, prescription dose and desired degree of heterogeneity within the target volume. It is unclear to what extent these differences in parameters might affect tumor control or toxicity, but updated consensus guidelines addressing the relevant SBRT prescription details may help standardize practice patterns.

Increased Resident Diversity Precedes Increased Faculty Diversity: Data From a University Radiation Oncology Department.

OBJECTIVES: Increasing the percentage of academic faculty who are female and/or an under-represented minority (URM) is a goal in radiation oncology. When studying diversity changes in our University Radiation Oncology Department, we found that increases in resident diversity preceded changes in faculty diversity in every major category. To illustrate these findings, we plotted resident versus faculty diversity each year over the 52-year history of our program. MATERIALS AND METHODS: Plots were generated of the percent of residents versus faculty in our program each year between 1967 and 2020 in the following categories: female, URM, and people of color. RESULTS: By 1995, substantial levels of diversity were present among both residents and faculty with approximate median annual values between 1995 and 2020 of 30% female for both residents and faculty, 15% URM for both residents and faculty, and 30% persons of color for residents and 15% for faculty. In all analyses, increase in resident diversity preceded an increase in faculty diversity and, in the great majority of years, resident diversity was greater than faculty diversity. CONCLUSION: Our experience suggests that it may be easier to increase resident than faculty diversity and that increases in resident diversity may facilitate increasing faculty diversity.

Orbital metastasis of squamous cell cervical cancer: A case report and review of literature.

Common sites of metastatic disease seen in cervical cancer most often include the lungs and liver. Orbital metastasis secondary to cervical carcinoma is a rare form of metastatic disease. We report a 73-year-old woman who presented with ocular symptoms found to be secondary to orbital metastasis of cervical cancer. She underwent palliative radiation to the orbit and pelvis followed by systemic chemotherapy with carboplatin, paclitaxel, and bevacizumab. Prompt intervention was able to salvage her vision and improve her quality of life significantly. We identified 5 similar reported cases in which orbital metastasis was diagnosed simultaneously at the time of cervical cancer diagnosis. In these five cases, patients were treated with a combination of radiation and chemotherapy. Our case demonstrates an unusual presentation of isolated orbital metastatic disease secondary to squamous cell carcinoma of the cervix. Physicians should be aware that cervical cancer may metastasize to the eye leading to vision loss, and prompt intervention may be able to salvage one's vision and improve quality of life.

Journey to Diversity in a University Radiation Oncology Residency Program: The Role of Leadership and Target Goals.

OBJECTIVES: Increasing diversity in radiation oncology with respect to sex, under-represented minorities (URMs), and people of color is a major objective of our profession. The purpose of this project is to plot diversity percentages in our residency program over the past 52 years and explain major causes for change when identified. MATERIALS AND METHODS: Plots of the percent of residents in our program each year between 1967 and 2020 in the following categories: White male, female, URM, and people of color. RESULTS: Between 1967 and 1992 diversity percentage in our program changed little with ∼90% of residents representing White males. Between 1992 and 1995, overall diversity increased by 40 percentage points, a change maintained from 1995 to 2020. Approximate annual percentages over the past 25 years were: female, 35%; URM, 10%; and people of color, 25%.The main reason for increased diversity starting in 1992 was new leadership seeking to promote diversity. Tools that helped promote diversity were measuring our diversity profile and setting target goals. CONCLUSIONS: Our experience provides a model to measure diversity and track performance over time in residency programs, departments, or practice groups. The priority to place on diversity, and specific performance goals, vary by group. For those seeking to increase diversity, our experience shows it is possible to achieve substantial diversity in all categories, but change requires leadership making diversity a priority.

A format for dosimetry comparison studies.

There is no standardized format for presenting and discussing the results of a radiotherapy dosimetry comparison study. The purpose of this report is to describe a format that we have found useful in evaluating plans in our department and in reviewing studies from other groups.

Improvement in Patient-Reported Outcomes With Intensity-Modulated Radiotherapy (RT) Compared With Standard RT: A Report From the NRG Oncology RTOG 1203 Study.

PURPOSE: In oncology trials, the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) is the standard tool for reporting adverse events (AEs), but it may underreport symptoms experienced by patients. This analysis of the NRG Oncology RTOG 1203 compared symptom reporting by patients and clinicians during radiotherapy (RT). PATIENTS AND METHODS: Patients with cervical or endometrial cancer requiring postoperative RT were randomly assigned to standard 4-field RT or intensity-modulated RT (IMRT). Patients completed the 6-item patient-reported outcomes version of the CTCAE (PRO-CTCAE) for GI toxicity assessing abdominal pain, diarrhea, and fecal incontinence at various time points. Patients reported symptoms on a 5-point scale. Clinicians recorded these AEs as CTCAE grades 1 to 5. Clinician- and patient-reported AEs were compared using McNemar's test for rates > 0%. RESULTS: Of 278 eligible patients, 234 consented and completed the PRO-CTCAE. Patients reported high-grade abdominal pain 19.1% (P < .0001), high-grade diarrhea 38.5% (P < .0001), and fecal incontinence 6.8% more frequently than clinicians. Similar effects were seen between grade ≥ 1 CTCAE toxicity and any-grade patient-reported toxicity. Between-arm comparison of patient-reported high-grade AEs revealed that at 5 weeks of RT, patients who received IMRT experienced fewer GI AEs than patients who received 4-field pelvic RT with regard to frequency of diarrhea (18.2% difference; P = .01), frequency of fecal incontinence (8.2% difference; P = .01), and interference of fecal incontinence (8.5% difference; P = .04). CONCLUSION: Patient-reported AEs showed a reduction in symptoms with IMRT compared with standard RT, whereas clinician-reported AEs revealed no difference. Clinicians also underreported symptomatic GI AEs compared with patients. This suggests that patient-reported symptomatic AEs are important to assess in this disease setting.

Immunotherapy with hypofractionated radiotherapy in metastatic non-small cell lung cancer: An analysis of the National Cancer Database.

PURPOSE: Metastatic non-small cell lung cancer (NSCLC) is associated with an exceedingly poor prognosis. Recent advances in immunotherapy offer promise in enhancing overall survival (OS) in these patients. Preclinical evidence suggests that radiotherapy (RT), especially when offered in a high-dose per fraction hypofractionated RT (HRT) as in stereotactic ablative body radiotherapy (SABR), may augment the efficacy of immunotherapy. We aimed to assess the role of RT in patients with metastatic NSCLC receiving immunotherapy in a national hospital-based database. METHODS: Using the National Cancer Database (NCDB), we identified 6,383 patients treated with immunotherapy for metastatic NSCLC and 170,479 patients treated with RT but without immunotherapy. Patients receiving fractional doses of at least 5 Gy were designated as having received HRT, doses <5 Gy/fraction, were deemed standard fractionation (SFRT). The Kaplan-Meier analysis and proportional hazards modeling were performed, and propensity scores were generated via an inverse weighting method to evaluate the impact of RT on OS in this cohort. RESULTS: The median follow-up of the cohort is 12 months. Patients receiving HRT had numerically improved 1-year OS (59.0%) compared to those not receiving RT (55.7%), however this was not statistically significant (hazard ratio = 0.9, p = 0.22). Patients receiving non-HRT RT did substantially worse than those receiving no RT. Immunotherapy improved OS in patients receiving RT regardless of fraction size. CONCLUSIONS: This hypothesis-generating retrospective analysis suggests that patients treated with immunotherapy with or without HRT in the upfront treatment of metastatic NSCLC experience similar survival. Further prospective evaluation of this combination should be undertaken in an attempt to maximize survival in this challenging disease.

Expanded validation of the EPIC bowel and urinary domains for use in women with gynecologic cancer undergoing postoperative radiotherapy.

OBJECTIVE: Women with endometrial or cervical cancer at risk for recurrence receive postoperative radiation therapy (RT). A patient reported outcomes (PRO) instrument to assess bowel and urinary toxicities is the Expanded Prostate Cancer Index Composite (EPIC), which has been validated in men with prostate cancer. As this instrument specifically measures bowel toxicity and the degree to which this is a problem, it was used in NRG Oncology/RTOG 1203 to compare intensity modulated RT (IMRT) to standard RT. This paper reports on the expanded validation of EPIC for use in women receiving pelvic RT. METHODS: In addition to the EPIC bowel domain, urinary toxicity (EPIC urinary domain), patient reported bowel toxicities (PRO-CTCAE) and quality of life (Functional Assessment of Cancer Therapy (FACT)) were completed before, during and after treatment. Sensitivity, reliability and concurrent validity were assessed. RESULTS: Mean bowel and urinary scores among 278 women enrolled were significantly worse during treatment and differed between groups. Acceptable to good reliability for bowel and urinary domain scores were obtained at all time points with the exception of one at baseline. Correlations between function and bother scores within the bowel and urinary domains were consistently stronger than those across domains. Correlations between bowel domain scores and PRO-CTCAE during treatment were stronger than those with the FACT. CONCLUSION: Correlations within and among the instruments indicate EPIC bowel and urinary domains are measuring conceptually discrete components of health. These EPIC domains are valid, reliable and sensitive instruments to measure PRO among women undergoing pelvic radiation.

Survivor and Caregiver Expectations and Preferences Regarding Lung Cancer Treatment.

PURPOSE: Treatment success in lung cancer is no longer restricted to objective measures of disease-specific outcomes and overall survival alone but now incorporates treatment morbidity and subjective quality of life (QoL). This study reports how lung cancer patients, survivors, and caregivers define treatment success and prioritize treatment decisions. MATERIALS AND METHODS: An online survey with both ranking and free-response questions was administered among lung cancer survivors and caregivers. Responses were used to evaluate treatment priorities, perceptions of treatment success based on Eastern Cooperative Oncology Group (ECOG) Performance Status, and troublesomeness of treatment-related toxicities. RESULTS: Among 61 respondents (29 lung cancer survivors, 28 caregivers of survivors, and 4 who were both survivors and caregivers), cancer cure was the highest priority when making treatment decisions for 74.5% of respondents, with QoL during and after treatment ranking second and third. Seventy percent of respondents felt that treatment morbidity resulting in complete dependence on others and spending the entire day confined to bed or chair would represent unsuccessful treatment. Requiring oxygen use was ranked as a very or extremely troublesome treatment toxicity by 64%, followed by shortness of breath (62%), fatigue (49%), chronic cough (34%), and appetite loss (30%). Even with remission, a 3- to 7-day hospital admission for pneumonia during treatment was deemed an unsuccessful outcome by 30%. CONCLUSION: This study highlights the importance of physicians discussing in detail with their lung cancer patients their desires and goals. Accounting for factors like expected performance status following treatment, troublesomeness of treatment toxicities, and hospitalization rates may help guide treatment decisions.

Patient-Reported Toxicity During Pelvic Intensity-Modulated Radiation Therapy: NRG Oncology-RTOG 1203.

Purpose NRG Oncology/RTOG 1203 was designed to compare patient-reported acute toxicity and health-related quality of life during treatment with standard pelvic radiation or intensity-modulated radiation therapy (IMRT) in women with cervical and endometrial cancer. Methods Patients were randomly assigned to standard four-field radiation therapy (RT) or IMRT radiation treatment. The primary end point was change in patient-reported acute GI toxicity from baseline to the end of RT, measured with the bowel domain of the Expanded Prostate Cancer Index Composite (EPIC). Secondary end points included change in patient-reported urinary toxicity, change in GI toxicity measured with the Patient-Reported Outcome Common Terminology Criteria for Adverse Events, and quality of life measured with the Trial Outcome Index. Results From 2012 to 2015, 289 patients were enrolled, of whom 278 were eligible. Between baseline and end of RT, the mean EPIC bowel score declined 23.6 points in the standard RT group and 18.6 points in the IMRT group ( P = .048), the mean EPIC urinary score declined 10.4 points in the standard RT group and 5.6 points in the IMRT group ( P = .03), and the mean Trial Outcome Index score declined 12.8 points in the standard RT group and 8.8 points in the IMRT group ( P = .06). At the end of RT, 51.9% of women who received standard RT and 33.7% who received IMRT reported frequent or almost constant diarrhea ( P = .01), and more patients who received standard RT were taking antidiarrheal medications four or more times daily (20.4% v 7.8%; P = .04). Conclusion Pelvic IMRT was associated with significantly less GI and urinary toxicity than standard RT from the patient's perspective.

Stereotactic Ablative Body Radiotherapy for Primary Non-Small-Cell Lung Cancer: Achieving Local Control with a Lower Biologically Effective Dose.

We conducted a retrospective study of stereotactic ablative radiotherapy (SABR) for 94 patients with non-small-cell lung cancer at our institution. The patients were treated with either 50 Gy in five treatments or 48 Gy in four treatments, corresponding to biologically effective doses (BED) of 100 Gy or 105.6 Gy, respectively. The results demonstrate that, with relatively low BEDs, we can achieve excellent local control with minimal toxicity.

Bevacizumab Eligibility in Patients with Metastatic and Recurrent Cervical Cancer: A Retrospective Review.

OBJECTIVE: Bevacizumab is approved for use in combination with chemotherapy for metastatic/recurrent cervical cancer (CC), with increased survival/response rates. However, use of bevacizumab is not always feasible or safe. The purpose of this study was to identify the percentage of metastatic/recurrent CC patients at our institution who would have been eligible to receive bevacizumab. METHODS: A retrospective study was conducted to identify metastatic/recurrent CC patients treated at UFHealth between 2006 and 2016. Chart review was performed to determine if the patient met bevacizumab eligibility criteria. RESULTS: In total, 79 patients with metastatic/recurrent CC were identified; 85.5% would have been ineligible to receive bevacizumab, and 14.5% would have been eligible. The most common reason for exclusion was active bleeding (68.4%); 94% of which was vaginal. In all, 27.6% would be excluded due to poor renal function, and 23.7% due to poor performance status (PS). CONCLUSIONS: Despite improved survival, only 14.5% of metastatic/recurrent CC patients treated over a 10-year period would have been eligible to receive bevacizumab. Most patients would have been excluded due to active bleeding, most commonly vaginal bleeding, a common complication from their disease. Identifying novel therapies for metastatic/recurrent CC patients with improved safety profiles that would allow for their use in this challenging population is critical.