Looking Back: International Practice Patterns in Breast Radiation Oncology From a Case-Based Survey Across 54 Countries During the First Surge of the COVID-19 Pandemic.

PURPOSE: The COVID-19 pandemic has profoundly affected cancer care worldwide, including radiation therapy (RT) for breast cancer (BC), because of risk-based resource allocation. We report the evolution of international breast RT practices during the beginning of the pandemic, focusing on differences in treatment recommendations between countries. MATERIALS AND METHODS: Between July and November 2020, a 58-question survey was distributed to radiation oncologists (ROs) through international professional societies. Changes in RT decision making during the first surge of the pandemic were evaluated across six hypothetical scenarios, including the management of ductal carcinoma in situ (DCIS), early-stage, locally advanced, and metastatic BC. The significance of changes in responses before and during the pandemic was examined using chi-square and McNemar-Bowker tests. RESULTS: One thousand one hundred three ROs from 54 countries completed the survey. Incomplete responses (254) were excluded from the analysis. Most respondents were from the United States (285), Japan (117), Italy (63), Canada (58), and Brazil (56). Twenty-one percent (230) of respondents reported treating at least one patient with BC who was COVID-19-positive. Approximately 60% of respondents reported no change in treatment recommendation during the pandemic, except for patients with metastatic disease, for which 57.7% (636/1,103; P < .0005) changed their palliative practice. Among respondents who noted a change in their recommendation during the first surge of the pandemic, omitting, delaying, and adopting short-course RT were the most frequent changes, with most transitioning to moderate hypofractionation for DCIS and early-stage BC. CONCLUSION: Early in the COVID-19 pandemic, significant changes in global RT practice patterns for BC were introduced. The impact of published results from the FAST FORWARD trial supporting ultrahypofractionation likely confounded the interpretation of the pandemic's independent influence on RT delivery.

Quantifying radiation in the axillary bed at the site of lymphedema surgical prevention.

PURPOSE: Immediate lymphatic reconstruction (ILR) is a procedure known to reduce the risk of lymphedema in patients undergoing axillary lymph node dissection (ALND). However, patients who receive adjuvant radiotherapy are at increased risk of lymphedema. The aim of this study was to quantify the extent of radiation at the site of surgical prevention. METHODS: We recently began deploying clips at the site of ILR to identify the site during radiation planning. A retrospective review was performed to identify breast cancer patients who underwent ILR with clip deployment and adjuvant radiation therapy from October 2020 to April 2022. Patients were excluded if they had not completed radiotherapy. The exposure and dose of radiation received by the site was determined and recorded. RESULTS: In a cohort of 11 patients, the site fell within the radiation field in 7 patients (64%) and received a median dose of 4280 cGy. Among these 7 patients, 3 had sites located within tissue considered at risk of oncologic recurrence and the remaining 4 sites received radiation from a tangential field treating the breast or chest wall. The median dose to the ILR site for the 4 patients whose sites were outside the radiation fields was 233 cGy. CONCLUSION: Our findings suggest that even when the site of surgical prevention was not within the targeted radiation field during treatment planning, it remains susceptible to radiation. Strategies for limiting radiation at this site are needed.

A Prospective Study of Radiation Therapy After Immediate Lymphatic Reconstruction: Analysis of the Dosimetric Implications.

PURPOSE: Axillary lymph node dissection (ALND) and regional nodal irradiation (RNI) are the primary causes of breast cancer-related lymphedema (BCRL). Immediate lymphatic reconstruction (ILR) is a novel surgical procedure that reduces the incidence of BCRL after ALND. The ILR anastomosis is placed in a location thought to be outside the standard radiation therapy fields to prevent radiation-induced fibrosis of the reconstructed vessels; however, there is excess risk of BCRL from RNI even after ILR. The purpose of this study was to understand the radiation dose distribution in relation to the ILR anastomosis. METHODS AND MATERIALS: This prospective study included 13 patients treated with ALND/ILR from October 2020 to June 2022. A twirl clip deployed during surgery was used to identify the ILR anastomosis site during radiation treatment planning. All cases were planned using a 3D-conformal technique with opposed tangents and an obliqued supraclavicular (SCV) field. RESULTS: RNI deliberately targeted axillary Levels 1 to 3 and the SCV nodal region in 4 patients and was limited to Level 3 and SCV nodes in 9 patients. The ILR clip was located in Level 1 in 12 patients and Level 2 in 1 patient. In patients with radiation directed at only Level 3 and SCV, the ILR clip was still within the radiation field in 5 of these patients and received a median dose of 3939 cGy (range, 2025-4961 cGy). The median dose to the ILR clip was 3939 cGy (range, 139-4961 cGy) for the entire cohort. The median dose was 4275 cGy (range, 2025-4961 cGy) when the ILR clip was within any radiation field and 233 cGy (range, 139-280 cGy) when the clip was outside all fields. CONCLUSION: The ILR anastomosis was often directly irradiated with 3D-conformal techniques and received substantial radiation dose, even when the site was not deliberately targeted. Long-term analysis will help determine whether minimizing radiation dose to the anastomosis will decrease BCRL rates.

Development and Implementation of an Educational Simulation Workshop in Fiberoptic Laryngoscopy for Radiation Oncology Residents.

PURPOSE: Fiberoptic laryngoscopy (FOL) is a critical tool for the diagnosis, staging, assessment of treatment response, and detection of recurrence for head and neck (H&N) malignancies. No standardized recommendations exist for procedural FOL education in radiation oncology. We therefore implemented a pilot simulation workshop to train radiation oncology residents in pertinent H&N anatomy and FOL technique. METHODS AND MATERIALS: A 2-phase workshop and simulation session was designed. Residents initially received a lecture on H&N anatomy and the logistics of the FOL examination. Subsequently, residents had a practical session in which they performed FOL in 2 simulated environments: a computerized FOL program and mannequin-based practice. Site-specific attending physicians were present to provide real-time guidance and education. Pre- and postworkshop surveys were administered to the participants to determine the impact of the workshop. Subsequently, postgraduate year (PGY)-2 residents were required to complete 6 supervised FOL examinations in clinic and were provided immediate feedback. RESULTS: Annual workshops were performed in 2017 to 2019. The survey completion rate was 14 of 18 (78%). Participants ranged from fourth-year medical students to PGY-2 to PGY-5 residents. All PGY-2 residents completed their 6 supervised FOL examinations. On a 5-point Likert scale, mean H&N anatomy knowledge increased from 2.4 to 3.7 (standard deviation = 0.6, P < .0001). Similarly, mean FOL procedural skill confidence increased from 2.2 to 3.3 (standard deviation = 0.7, P < .0001). These effects were limited to novice (fourth-year medical students to PGY-2) participants. All participants found the exercise clinically informative. CONCLUSIONS: A simulation-based workshop for teaching FOL procedural skills increased confidence and procedural expertise of new radiation oncology residents and translated directly to supervised clinical encounters. Adoption of this type of program may help to improve resident training in H&N cancer.

Survival Advantage With Adjuvant Chemotherapy for Locoregionally Advanced Rectal Cancer: A Veterans Health Administration Analysis.

BACKGROUND: Adjuvant chemotherapy (AC) after chemoradiation (CRT) and surgery for locoregionally advanced rectal cancer (LARC) is a standard of care in the United States. This study examined the role, optimal regimen, and duration of AC using data from the largest integrated health system in the United States. PATIENTS AND METHODS: Using the Veterans Affairs Central Cancer Registry, patients with stage II-III rectal cancer diagnosed in 2001 through 2011 who received neoadjuvant CRT and surgery with or without AC were identified. Kaplan-Meier analysis, log-rank tests, and propensity score (PS) adjustment analysis were used to assess survival. RESULTS: A total of 866 patients were identified; 417 received AC and 449 did not (observation [OBS] group). Median follow-up was 109 months. Median disease-specific survival (DSS) was not reached. Six-year DSS was 73.7%; 79.5% for the AC group versus 68.0% for the OBS group. PS-matched analysis for DSS favored AC (P=.0002). Median overall survival (OS) was 90.8 months. Six-year OS was 56.7%; 64.3% for AC versus 49.6% for OBS. In PS-matched analysis, median OS was 117.4 months for AC and 74.3 months for OBS (P<.0001). A DSS advantage was seen when comparing ≥4 months with <4 months of AC (P=.023). No difference in DSS or OS was seen with single-agent versus multiagent AC. CONCLUSIONS: In this population of patients with LARC treated with neoadjuvant CRT and surgery, OS and DSS were improved among those treated with AC versus OBS. DSS benefits were seen with ≥4 months of AC. No additional benefit was observed with multiagent therapy. In the absence of phase III data, these findings support the use of AC for LARC.

Increasing PET Use in Small Cell Lung Cancer: Survival Improvement and Stage Migration in the VA Central Cancer Registry.

Background: Accurate staging for small cell lung cancer (SCLC) is critical for determining appropriate therapy. The clinical impact of increasing PET adoption and stage migration is well described in non-small cell lung cancer but not in SCLC. The objective of this study was to evaluate temporal trends in PET staging and survival in the Veterans Affairs Central Cancer Registry and the impact of PET on outcomes. Patients and Methods: Patients diagnosed with SCLC from 2001 to 2010 were identified. PET staging, overall survival (OS), and lung cancer-specific survival (LCSS) were assessed over time. The impact of PET staging on OS and LCSS was assessed for limited-stage (LS) and extensive-stage (ES) SCLC. Results: From 2001 to 2010, PET use in a total of 10,135 patients with SCLC increased from 1.1% to 39.2%. Median OS improved for all patients (from 6.2 to 7.9 months), those with LS-SCLC (from 10.9 to 13.2 months), and those with ES-SCLC (from 5.0 to 7.0 months). Among staged patients, the proportion of ES-SCLC increased from 63.9% to 65.7%. Among 1,536 patients with LS-SCLC treated with concurrent chemoradiotherapy, 397 were staged by PET. In these patients, PET was associated with longer OS (median, 19.8 vs 14.3 months; hazard ratio [HR], 0.78; 95% CI, 0.68-0.90; P<.0001) and LCSS (median, 22.9 vs 16.7 months; HR, 0.74; 95% CI, 0.63-0.87; P<.0001) with multivariate adjustment and propensity-matching. In the 6,143 patients with ES-SCLC, PET was also associated with improved OS and LCSS. Conclusions: From 2001 to 2010, PET staging increased in this large cohort, with a corresponding relative increase in ES-SCLC. PET was associated with greater OS and LCSS for LS-SCLC and ES-SCLC, likely reflecting stage migration and stage-appropriate therapy. These findings emphasize the importance of PET in SCLC and support its routine use.

A Nomogram for Testosterone Recovery After Combined Androgen Deprivation and Radiation Therapy for Prostate Cancer.

PURPOSE: Testosterone recovery (TR) after androgen deprivation therapy (ADT) and radiation therapy (RT) is not well characterized. We studied TR in men who received RT and either short-term ADT (STADT) or long-term ADT (LTADT) and aimed to create a nomogram to predict TR. METHODS AND MATERIALS: We identified consecutive localized prostate cancer patients treated with ADT-RT at 2 academic medical centers from January 2011 to October 2016 with documented baseline testosterone. TR was time from last ADT injection to testosterone normalization. The Kaplan-Meier method was used to estimate time to TR. Cox proportional hazards models identified TR predictors. A nomogram was trained with site 1 and externally validated with site 2. RESULTS: A total of 340 patients were included; 69.7% received STADT for a median duration of 6 months; 30.3% received LTADT for a median duration of 24.3 months. Median follow-up was 26.7 months. Median time for TR was 17.2 months for STADT and 24.0 months for LTADT patients (P = .004). The 2-year cumulative incidence of TR was 53.1% after LTADT versus 65.7% after STADT (P = .004). On multivariate analysis, shorter duration ADT (hazard ratio [HR], 0.96; P = .004), higher pretreatment testosterone (HR, 1.004; P < .001), and lower body mass index (HR, 0.95; P = .002) were associated with shorter time to TR. Older age (HR, 0.97; P = .09) and white race (HR, 0.67; P = .06) trended as longer TR predictors. A nomogram was generated to predict probability of TR at 1, 2, and 3 years. The concordance index was 0.71 (95% confidence interval, 0.64-0.78) for the validation cohort. CONCLUSIONS: In this population of localized prostate cancer patients, TR after ADT-RT was variable. Using baseline testosterone, ADT duration, body mass index, age, and race, a predictive nomogram can estimate the likelihood of TR.

Changes in insurance coverage for cancer patients receiving brachytherapy before and after enactment of the Affordable Care Act.

PURPOSE: The Patient Protection and Affordable Care Act called for expansion of Medicaid in 2014. As some states elected to expand Medicaid and others did not, the goal of this study was to determine the effect of Medicaid expansion on the insurance status at cancer diagnosis of brachytherapy patients. METHODS AND MATERIALS: Patients aged 19-64 years with breast, cervical, uterine, or prostate cancer treated with brachytherapy from 2011 to 2014 with known insurance status were identified within the Surveillance, Epidemiology, and End Results registry. Fisher's exact test was used to test for associations of insurance status with expanded versus nonexpanded states. For multivariate analysis, a binomial logistic regression was performed, dichotomized to uninsured versus any insurance. RESULTS: Fifteen thousand four hundred ninety-seven subjects met entry criteria. In the entire cohort, rates of uninsurance were higher in nonexpanded states at baseline (4.5% vs. 2.9%, p < 0.00001). With selective Medicaid expansion in 2014, expanded states had a reduction in uninsurance rates (2.9-1.8%, p = 0.026), whereas nonexpanded states had a nonsignificant increase in uninsurance (4.5-5.0%, p = 0.371). There was a reduction in uninsurance in expanded states in areas of highest poverty (2.9-1.1%, p = 0.0004) not seen in nonexpanded states. These associations remained significant on multivariate analysis (OR 2.2, 95% CI 1.8-2.8, p < 0.00001). CONCLUSIONS: Patients who received brachytherapy were less likely to be uninsured in states where Medicaid was expanded, particularly evident in regions with highest poverty levels. These results should help inform policy decisions and efforts to ensure that all patients have access to high quality treatments, such as brachytherapy.

Long-term Clinical Outcomes of Nonoperative Management With Chemoradiotherapy for Locally Advanced Rectal Cancer in the Veterans Health Administration.

PURPOSE: Standard therapy for locally advanced rectal cancer includes neoadjuvant chemoradiation and surgery. Complete response (CR) rates after chemoradiation can be as high as 29%, suggesting that nonoperative management (NOM) may be reasonable with appropriately selected patients. We sought to identify potential NOM candidates. METHODS AND MATERIALS: Using the Veterans Administration Central Cancer Registry, patients with stage II to III rectal cancer receiving chemoradiation with or without subsequent surgery were identified. Clinical CR (cCR) was assessed by physical examination, endoscopy, or imaging. Kaplan-Meier and log-rank tests were used to assess survival; multivariate analysis was performed using Cox proportional hazards. RESULTS: A total of 1313 patients were identified. Of these, 313 received chemoradiation alone (CRT cohort); 1000 received chemoradiation followed by surgery (CRT + S cohort). Median follow-up was 67.2 months. Median overall survival (OS) was 68.5 months. Median OS was 30.6 months for CRT and 89.3 months for CRT + S (P < .001). Median disease-specific survival (DSS) was 44.8 months for CRT and not reached (NR) for CRT + S (P < .001). Sixty-five CRT patients (20.8%) had a cCR. Median OS for CRT cCR patients was 73.5 months (P = .128 vs CRT + S); median DSS was NR (P = .161 vs CRT + S). One hundred thirty-seven (10.5%) CRT + S patients had a pathologic CR (pCR). Median OS with pCR was 133.7 months (P < .001 vs CRT cCR), and median DSS was NR (P = .276 vs CRT cCR). CONCLUSIONS: CRT patients with cCR had similar OS and DSS versus CRT + S patients and similar DSS versus CRT + S patients with a pCR. This suggests that patients with locally advanced rectal cancer with a cCR to CRT have an excellent prognosis and may be candidates for organ preservation.

High-volume providers and brachytherapy practice: A Medicare provider utilization and payment analysis.

PURPOSE: Brachytherapy is an important component of the treatment of gynecologic and prostate cancers, with data supporting its impact on clinical outcomes. Prior data have suggested that brachytherapy tends to be focused at high-volume centers. Medicare reimbursement data can provide an understanding of the distribution of brachytherapy cases among billing providers. The objective of this study is to quantify the distribution of brachytherapy cases and high volume providers. METHODS AND MATERIALS: The Medicare Physician and Other Supplier Public Use File was queried for individual physicians who had performed brachytherapy for more than 10 patients with gynecologic or prostate cancer in the years 2012-2015. Aggregate data were also queried. Trends were identified, and basic summary statistics were tabulated. RESULTS: During the study period, there was an increase in vaginal brachytherapy (3328 unique cases in 2012-4308 in 2015) but a decrease in intrauterine implants, such as tandem placements (1522 in 2012-1307 in 2015) and prostate brachytherapy (8860 in 2012-6527 in 2015). High-volume providers treating more than 10 patients represented a disproportionate number of patients treated, particularly with intra-uterine brachytherapy, representing no more than 1.2% of the active providers in a given year but up to 11.1% of intra-uterine brachytherapy cases. CONCLUSIONS: Among Medicare claims, a small number of providers accounted for a significant proportion of gynecologic and prostate brachytherapy cases, particularly in the case of intrauterine implants. The vast majority of brachytherapy providers perform limited cases in this population. Efforts toward improving access to intrauterine implants in Medicare patients should be a national priority.

Outcomes of proton therapy for patients with functional pituitary adenomas.

PURPOSE/OBJECTIVE(S): This study evaluated the efficacy and toxicity of proton therapy for functional pituitary adenomas (FPAs). METHODS AND MATERIALS: We analyzed 165 patients with FPAs who were treated at a single institution with proton therapy between 1992 and 2012 and had at least 6 months of follow-up. All but 3 patients underwent prior resection, and 14 received prior photon irradiation. Proton stereotactic radiosurgery was used for 92% of patients, with a median dose of 20 Gy(RBE). The remainder received fractionated stereotactic proton therapy. Time to biochemical complete response (CR, defined as ≥ 3 months of normal laboratory values with no medical treatment), local control, and adverse effects are reported. RESULTS: With a median follow-up time of 4.3 years (range, 0.5-20.6 years) for 144 evaluable patients, the actuarial 3-year CR rate and the median time to CR were 54% and 32 months among 74 patients with Cushing disease (CD), 63% and 27 months among 8 patients with Nelson syndrome (NS), 26% and 62 months among 50 patients with acromegaly, and 22% and 60 months among 9 patients with prolactinomas, respectively. One of 3 patients with thyroid stimulating hormone-secreting tumors achieved CR. Actuarial time to CR was significantly shorter for corticotroph FPAs (CD/NS) compared with other subtypes (P=.001). At a median imaging follow-up time of 43 months, tumor control was 98% among 140 patients. The actuarial 3-year and 5-year rates of development of new hypopituitarism were 45% and 62%, and the median time to deficiency was 40 months. Larger radiosurgery target volume as a continuous variable was a significant predictor of hypopituitarism (adjusted hazard ratio 1.3, P=.004). Four patients had new-onset postradiosurgery seizures suspected to be related to generously defined target volumes. There were no radiation-induced tumors. CONCLUSIONS: Proton irradiation is an effective treatment for FPAs, and hypopituitarism remains the primary adverse effect.

Long-term outcomes of selective bladder preservation by combined-modality therapy for invasive bladder cancer: the MGH experience.

BACKGROUND: Whether organ-conserving treatment by combined-modality therapy (CMT) achieves comparable long-term survival to radical cystectomy (RC) for muscle-invasive bladder cancer (BCa) is largely unknown. OBJECTIVE: Report long-term outcomes of patients with muscle-invasive BCa treated by CMT. DESIGN, SETTING, AND PARTICIPANTS: We conducted an analysis of successive prospective protocols at the Massachusetts General Hospital (MGH) treating 348 patients with cT2-4a disease between 1986 and 2006. Median follow-up for surviving patients was 7.7 yr. INTERVENTIONS: Patients underwent concurrent cisplatin-based chemotherapy and radiation therapy (RT) after maximal transurethral resection of bladder tumor (TURBT) plus neoadjuvant or adjuvant chemotherapy. Repeat biopsy was performed after 40 Gy, with initial tumor response guiding subsequent therapy. Those patients showing complete response (CR) received boost chemotherapy and RT. One hundred two patients (29%) underwent RC-60 for less than CR and 42 for recurrent invasive tumors. MEASUREMENTS: Disease-specific survival (DSS) and overall survival (OS) were evaluated using the Kaplan-Meier method. RESULTS AND LIMITATIONS: Seventy-two percent of patients (78% with stage T2) had CR to induction therapy. Five-, 10-, and 15-yr DSS rates were 64%, 59%, and 57% (T2=74%, 67%, and 63%; T3-4=53%, 49%, and 49%), respectively. Five-, 10-, and 15-yr OS rates were 52%, 35%, and 22% (T2: 61%, 43%, and 28%; T3-4=41%, 27%, and 16%), respectively. Among patients showing CR, 10-yr rates of noninvasive, invasive, pelvic, and distant recurrences were 29%, 16%, 11%, and 32%, respectively. Among patients undergoing visibly complete TURBT, only 22% required cystectomy (vs 42% with incomplete TURBT; log-rank p<0.001). In multivariate analyses, clinical T-stage and CR were significantly associated with improved DSS and OS. Use of neoadjuvant chemotherapy did not improve outcomes. No patient required cystectomy for treatment-related toxicity. CONCLUSIONS: CMT achieves a CR and preserves the native bladder in >70% of patients while offering long-term survival rates comparable to contemporary cystectomy series. These results support modern bladder-sparing therapy as a proven alternative for selected patients.

Prostatic duct adenocarcinoma: clinical characteristics, treatment options, and outcomes - a Rare Cancer Network study.

BACKGROUND: To evaluate the clinical characteristics, contemporary treatment options, and outcome of prostatic duct adenocarcinoma (PDA), we initiated a Rare Cancer Network (RCN) study. MATERIALS AND METHODS: Six member institutions of the RCN collected clinical data on 31 patients. Treatment consisted of definitive radiotherapy in 14 patients and radical prostatectomy in 16 patients. One patient was treated with androgen deprivation alone. The mean follow-up period was 56 months. RESULTS: Of the 14 patients managed with radiotherapy, 1 patient developed bone metastases and died of prostate cancer, and 1 patient had a biochemical relapse 8 years after definitive radiotherapy. Of the 16 patients who underwent radical prostatectomy, 2 patients developed bone metastases, one of who died of disease. Three patients that relapsed after prostatectomy were successfully salvaged with radiotherapy. The patient that was treated with androgen deprivation alone developed bone metastases at 10 months, was treated with chemotherapy, and was alive after 22 months. CONCLUSIONS: Our results suggest that PDA is a cancer with a behavior similar to that of high Gleason grade acinar carcinoma. Good local control can be achieved by either radiation or surgery. Postoperative radiotherapy seems to work as an adjuvant or salvage treatment, and most tumors appear to respond to androgen deprivation.

Randomized trial comparing conventional-dose with high-dose conformal radiation therapy in early-stage adenocarcinoma of the prostate: long-term results from proton radiation oncology group/american college of radiology 95-09.

PURPOSE To test the hypothesis that increasing radiation dose delivered to men with early-stage prostate cancer improves clinical outcomes. PATIENTS AND METHODS Men with T1b-T2b prostate cancer and prostate-specific antigen /= 3 genitourinary toxicity, and 1% of patients in the high-dose arm experienced late grade >/= 3 GI toxicity. CONCLUSION This randomized controlled trial shows superior long-term cancer control for men with localized prostate cancer receiving high-dose versus conventional-dose radiation. This was achieved without an increase in grade >/= 3 late urinary or rectal morbidity.