Prostate Cancer Radiation Therapy Recommendations in Response to COVID-19.

PURPOSE: During a global pandemic, the benefit of routine visits and treatment of patients with cancer must be weighed against the risks to patients, staff, and society. Prostate cancer is one of the most common cancers radiation oncology departments treat, and efficient resource utilization is essential in the setting of a pandemic. Herein, we aim to establish recommendations and a framework by which to evaluate prostate radiation therapy management decisions. METHODS AND MATERIALS: Radiation oncologists from the United States and the United Kingdom rapidly conducted a systematic review and agreed upon recommendations to safely manage patients with prostate cancer during the COVID-19 pandemic. A RADS framework was created: remote visits, and avoidance, deferment, and shortening of radiation therapy was applied to determine appropriate approaches. RESULTS: Recommendations were provided by the National Comprehensive Cancer Network risk group regarding clinical node-positive, postprostatectomy, oligometastatic, and low-volume M1 disease. Across all prostate cancer stages, telemedicine consultations and return visits were recommended when resources/staff available. Delays in consultations and return visits of between 1 and 6 months were deemed safe based on stage of disease. Treatment can be avoided or delayed until safe for very low, low, and favorable intermediate-risk disease. Unfavorable intermediate-risk, high-risk, clinical node-positive, recurrence postsurgery, oligometastatic, and low-volume M1 disease can receive neoadjuvant hormone therapy for 4 to 6 months as necessary. Ultrahypofractionation is preferred for localized, oligometastatic, and low-volume M1, and moderate hypofractionation is preferred for postprostatectomy and clinical node positive disease. Salvage is preferred to adjuvant radiation. CONCLUSIONS: Resources can be reduced for all identified stages of prostate cancer. The RADS (remote visits, and avoidance, deferment, and shortening of radiation therapy) framework can be applied to other disease sites to help with decision making in a global pandemic.

Prostate Cancer Radiation Therapy Recommendations in Response to COVID-19.

PURPOSE: During a global pandemic, the benefit of routine visits and treatment of patients with cancer must be weighed against the risks to patients, staff, and society. Prostate cancer is one of the most common cancers radiation oncology departments treat, and efficient resource utilization is essential in the setting of a pandemic. Herein, we aim to establish recommendations and a framework by which to evaluate prostate radiation therapy management decisions. METHODS AND MATERIALS: Radiation oncologists from the United States and the United Kingdom rapidly conducted a systematic review and agreed upon recommendations to safely manage patients with prostate cancer during the COVID-19 pandemic. A RADS framework was created: remote visits, and avoidance, deferment, and shortening of radiation therapy was applied to determine appropriate approaches. RESULTS: Recommendations were provided by the National Comprehensive Cancer Network risk group regarding clinical node-positive, postprostatectomy, oligometastatic, and low-volume M1 disease. Across all prostate cancer stages, telemedicine consultations and return visits were recommended when resources/staff available. Delays in consultations and return visits of between 1 and 6 months were deemed safe based on stage of disease. Treatment can be avoided or delayed until safe for very low, low, and favorable intermediate-risk disease. Unfavorable intermediate-risk, high-risk, clinical node-positive, recurrence postsurgery, oligometastatic, and low-volume M1 disease can receive neoadjuvant hormone therapy for 4 to 6 months as necessary. Ultrahypofractionation is preferred for localized, oligometastatic, and low-volume M1, and moderate hypofractionation is preferred for postprostatectomy and clinical node positive disease. Salvage is preferred to adjuvant radiation. CONCLUSIONS: Resources can be reduced for all identified stages of prostate cancer. The RADS (remote visits, and avoidance, deferment, and shortening of radiation therapy) framework can be applied to other disease sites to help with decision making in a global pandemic.

Dramatic polarization in genitourinary expert opinions regarding the clinical utility of positron emission tomography (PET) imaging in prostate cancer

ABSTRACT Objectives: To ascertain the opinions of North American genitourinary (GU) experts regarding inclusion of technologies such as prostate - specific membrane antigen (PSMA) and C - 11 choline positron emission tomography (PET) into routine practice. Materials and Methods: A survey was distributed to North American GU experts. Questions pertained to the role of PSMA and C - 11 PET in PCa management. Participants were categorized as "supporters" or "opponents" of incorporation of novel imaging techniques. Opinions were correlated with practice patterns. Results: Response rate was 54% and we analyzed 42 radiation oncologist respondents. 17 participants (40%) have been in practice for > 20 years and 38 (90%) practice at an academic center. 24 (57%) were supporters of PSMA and 29 (69%) were supporters of C - 11. Supporters were more likely to treat pelvic nodes (88% vs. 56%, p < 01) and trended to be more likely to treat patients with moderate or extreme hypofractionation (58% vs. 28%, p = 065). Supporters trended to be more likely to offer brachytherapy boost (55% vs. 23%, p = 09), favor initial observation and early salvage over adjuvant radiation (77% vs. 55%, p = 09), and to consider themselves expert brachytherapists (69% vs. 39%, p = 09). Conclusions: There is a polarization among GU radiation oncology experts regarding novel imaging techniques. A correlation emerged between support of novel imaging and adoption of treatment approaches that are clinically superior or less expensive. Pre - existing biases among GU experts on national treatment - decision panels and leaders of cooperative group studies may affect the design of future studies and influence the adoption of these technologies in clinical practice.

Dramatic polarization in genitourinary expert opinions regarding the clinical utility of positron emission tomography (PET) imaging in prostate cancer.

OBJECTIVES: To ascertain the opinions of North American genitourinary (GU) experts regarding inclusion of technologies such as prostate - specific membrane antigen (PSMA) and C - 11 choline positron emission tomography (PET) into routine practice. MATERIALS AND METHODS: A survey was distributed to North American GU experts. Questions pertained to the role of PSMA and C - 11 PET in PCa management. Participants were categorized as "supporters" or "opponents" of incorporation of novel imaging techniques. Opinions were correlated with practice patterns. RESULTS: Response rate was 54% and we analyzed 42 radiation oncologist respondents. 17 participants (40%) have been in practice for > 20 years and 38 (90%) practice at an academic center. 24 (57%) were supporters of PSMA and 29 (69%) were supporters of C - 11. Supporters were more likely to treat pelvic nodes (88% vs. 56%, p < 01) and trended to be more likely to treat patients with moderate or extreme hypofractionation (58% vs. 28%, p = 065). Supporters trended to be more likely to offer brachytherapy boost (55% vs. 23%, p = 09), favor initial observation and early salvage over adjuvant radiation (77% vs. 55%, p = 09), and to consider themselves expert brachytherapists (69% vs. 39%, p = 09). CONCLUSIONS: There is a polarization among GU radiation oncology experts regarding novel imaging techniques. A correlation emerged between support of novel imaging and adoption of treatment approaches that are clinically superior or less expensive. Pre - existing biases among GU experts on national treatment - decision panels and leaders of cooperative group studies may affect the design of future studies and influence the adoption of these technologies in clinical practice.

Radiation Dose and Fractionation for Limited-stage Small-cell Lung Cancer: Survey of US Radiation Oncologists on Practice Patterns.

BACKGROUND: Thoracic radiotherapy (TRT) with concurrent chemotherapy is standard for limited-stage small-cell lung cancer (LS-SCLC). However, the optimal dosing and fractionation remain unclear. The National Comprehensive Cancer Network guidelines have recommended either 45 Gy delivered twice daily (BID) or 60 to 70 Gy delivered once daily (QD). However, the current practice patterns among US radiation oncologists are unknown. MATERIALS AND METHODS: We surveyed US radiation oncologists using an institutional review board-approved questionnaire. The questions covered demographic data, self-rated knowledge of key trials, and treatment recommendations. RESULTS: We received 309 responses from radiation oncologists. Of the 309 radiation oncologists, 60% preferred TRT QD and 76% acknowledged QD to be more common in their practice. The respondents in academic settings were more likely to endorse BID treatment by both preference (P = .001) and actual practice (P = .009). The concordance between preferring QD and administering QD in practice was 100%. In contrast, 40% of respondents who preferred BID actually administered QD more often. Also, 15% of physicians would be unwilling to switch from QD to BID and 3% would be unwilling to switch from BID to QD, even on patient request. Most respondents (88%) recommended a dose of 45 Gy for BID treatment. For QD treatment, the division was greater, with 54% recommending 60 Gy, 30% recommending 63 to 66 Gy, and 10% recommending 70 Gy. CONCLUSION: Substantial variation exists in how US radiation oncologists approach TRT dosing and fractionation for LS-SCLC. Three quarters of our respondents reported administering TRT QD most often. The most common doses were 60 Gy QD and 45 Gy BID. The results of the present survey have provided the most up-to-date information on US practice patterns for LS-SCLC.

Tumor Treating Fields Utilization in a Glioblastoma Patient with a Preexisting Cardiac Pacemaker: The First Reported Case.

BACKGROUND: Tumor-treating fields (TTFs) have become an important, evidence-based modality in the treatment of glioblastoma (GBM). In patients requiring cardiac pacemakers, TTF therapy is complicated by theoretical concerns regarding possible electrical interaction between the devices. CASE DESCRIPTION: A 57-year-old man with past medical history of sick sinus syndrome requiring cardiac pacemaker implantation suffered an acute neurologic change associated with a left parieto-occipital lesion, which was found to be GBM. After completion of guideline-concordant chemoradiation, he chose to undergo TTF therapy. Because of the absence of cardiac symptoms and the theoretical risk of far-field sensing by the pacemaker of the TTF device (potentially resulting in pacemaker inhibition), the pacemaker was turned off before receiving TTF. Following TTF implementation, the patient responded well; he remains alive more than 25 months following his GBM diagnosis, exceeding the median 20.9-month survival of the recently completed phase III TTF randomized clinical trial for newly diagnosed GBM. Furthermore, he has exhibited neither cardiac morbidity nor adverse scalp reactions to TTF therapy. CONCLUSIONS: The first reported case of successful TTF administration in a GBM patient with a previously implanted cardiac pacemaker may allay the concerns of neuro-oncologists, cardiologists, radiation oncologists, and all certified TTF prescribers regarding the applicability of TTF in suitable candidates with preexisting cardiac pacemakers. This case indicates that TTF therapy may be efficacious in patients with indwelling magnetic resonance image-conditional cardiac pacemakers turned to the off position and that physical removal of the pacemaker is not necessary before starting TTF.

Application of tumor treating fields for newly diagnosed glioblastoma: understanding of nationwide practice patterns.

BACKGROUND: Tumor treating fields (TTF) harness magnetic fields to induce apoptosis in targeted regions. A 2015 landmark randomized phase III trial of newly diagnosed glioblastoma (GBM) patients demonstrated TTF + temozolomide to be superior to temozolomide alone. Given these results, we sought to assess practice patterns of providers in TTF utilization for GBM. METHODS: A survey was administered to practices in the United States self-identifying as specializing in radiation oncology, medical oncology, neuro-oncology, neurosurgery, and/or neurology. Responses were collected anonymously; analysis was performed using Fisher's exact test. RESULTS: A total of 106 providers responded; a minority (36%) were in private practice. Regarding case volume, 82% treated at least six high-grade gliomas/year. The provider most commonly certified to offer TTF therapy to GBM patients was the neuro-oncologist (40%), followed by the radiation oncologist (34%); 31% reported no TTF-certified physician in their practice. TTF users were more likely to have high volume, and be aware of TTF inclusion in National Comprehensive Cancer Network (NCCN) guidelines (p < 0.05). CONCLUSIONS: More than 80% of TTF for GBM in the United States is performed by groups who treat at least six high-grade gliomas per year; unfortunately more than 30% were in practices bereft of anyone certified to offer TTF therapy. These results indicate that there remains fertile soil for TTF therapy nationwide to be introduced into practices for GBM treatment. Providers seeking to refer newly diagnosed GBM patients for TTF should seek out practices with TTF user-associated characteristics to ensure optimal access for their patients.

Timing of Thoracic Radiation Therapy With Chemotherapy in Limited-stage Small-cell Lung Cancer: Survey of US Radiation Oncologists on Current Practice Patterns.

INTRODUCTION: For limited-stage small-cell lung cancer (LS-SCLC), National Comprehensive Cancer Network guidelines recommend that thoracic radiotherapy (TRT) be delivered concurrently with chemotherapy and early in the regimen, with cycle 1 or 2. Evidence is conflicting regarding the benefit of early timing of TRT. A Korean randomized trial did not see a survival difference between early (cycle 1) and late (cycle 3) TRT. Current United States (US) practice patterns are unknown. MATERIALS AND METHODS: We surveyed US radiation oncologists using an institutional review board-approved online questionnaire. Questions covered treatment recommendations, self-rated knowledge of trials, and demographics. RESULTS: We received 309 responses from radiation oncologists. Ninety-eight percent recommend concurrent chemoradiotherapy over sequential. Seventy-one percent recommend starting TRT in cycle 1 of chemotherapy, and 25% recommend starting in cycle 2. In actual practice, TRT is started most commonly in cycle 2 (48%) and cycle 1 (44%). One-half of respondents (54%) believe starting in cycle 1 improves survival compared with starting in cycle 3. Knowledge of the Korean trial was associated with flexibility in delaying TRT to cycle 2 or 3 (P = .02). Over one-third (38%) treat based on pre-chemotherapy volume. CONCLUSION: US radiation oncologists strongly align with National Comprehensive Cancer Network guidelines, which recommend early concurrent chemoradiotherapy. Nearly three-quarters of respondents prefer starting TRT with cycle 1 of chemotherapy. However, knowledge of a trial supporting a later start was associated with flexibility in delaying TRT. Treating based on pre-chemotherapy volume-endorsed by over one-third of respondents-may add unnecessary toxicity. This survey can inform development of future trials.

Prophylactic Cranial Irradiation for Limited-Stage Small-Cell Lung Cancer: Survey of US Radiation Oncologists on Current Practice Patterns.

PURPOSE: Prophylactic cranial irradiation (PCI) in patients with limited-stage small-cell lung cancer (LS-SCLC) is considered the standard of care. Meta-analysis of 7 clinical trials indicates a survival benefit to PCI, but all of these trials were conducted in the pre-magnetic resonance imaging (MRI) era. Therefore, routine brain imaging with MRI before PCI-as recommended by National Comprehensive Cancer Network guidelines-is not directly supported by the evidence. Current US practice patterns for patients with LS-SCLC are unknown. MATERIALS AND METHODS: We surveyed practicing US radiation oncologists via an institutional review board-approved online questionnaire. Questions covered demographic information and treatment recommendations for LS-SCLC. RESULTS: We received 309 responses from US radiation oncologists. Ninety-eight percent recommended PCI for patients with LS-SCLC, 96% obtained brain MRI before PCI, 33% obtained serial brain imaging with MRI after PCI to detect new metastases, and 35% recommended memantine for patients undergoing PCI. Recommending memantine was associated with fewer years of practice (P < .001), fewer lung cancer patients treated per year (P = .045), and fewer LS-SCLC patients treated per year (P = .024). CONCLUSION: Almost all responding radiation oncologists recommended PCI and pre-PCI brain MRI for LS-SCLC patients with disease responsive to initial therapy. Only a third of respondents followed these patients with serial brain MRI. Approximately one third provided memantine therapy to try to limit neurocognitive effects of PCI. Further research is warranted to determine the best treatment for patients with LS-SCLC. This survey can inform the development of future trials that depend on participation from radiation oncologists.

Practice Patterns of Thoracic Radiotherapy for Extensive-Stage Small-Cell Lung Cancer: Survey of US Academic Thoracic Radiation Oncologists.

PURPOSE: Despite the recent CREST trial demonstrating a survival benefit to thoracic radiotherapy (TRT) for patients with extensive-stage small-cell lung cancer (ES-SCLC) with response to chemotherapy, as well as endorsement by current National Comprehensive Cancer Network guidelines, TRT may not be uniformly delivered in clinical practice across all circumstances. METHODS AND MATERIALS: We surveyed US academic thoracic radiation oncologists regarding their practice patterns for TRT and assessed conditions in which withholding TRT could be warranted. A 27-question survey of demographics and practice patterns, including 5 clinical cases, was sent to 111 physicians. RESULTS: Response rate was 39% (43/111). Among respondents, 60% have at least 6 years of work experience following residency; 77% and 71% respectively see > 50 lung cancer and > 11 SCLC cases annually. Regarding practice patterns, 74% use TRT in 26% to 75% of patients with ES-SCLC. Respondents would withhold TRT in cases with Eastern Cooperative Oncology Group performance status ≥ 3 (91%), when pulmonary function necessitates continuous oxygen via nasal cannula (62%), for postchemotherapy tumor progression (58%), and if > 4 postchemotherapy extrathoracic metastases were present (58%). The 5 clinical cases highlighted practice variability, although 1 case had 100% agreement among respondents. CONCLUSIONS: Despite support of TRT administration from the CREST trial, there are several conditions associated with frequently withholding TRT. The most common reasons include performance status, postchemotherapy extent of disease, and pulmonary function; age and prechemotherapy extent of disease were least associated. Further research should aim to identify which subgroups of ES-SCLC benefit most from TRT.

Current patterns of care for patients with extensive stage small cell lung cancer: Survey of US radiation oncologists on their recommendations regarding thoracic consolidation radiotherapy.

OBJECTIVES: Current National Comprehensive Cancer Network (NCCN) guidelines recommend thoracic consolidation radiation therapy (TCRT) for patients with Extensive Stage Small Cell Lung Cancer (ES-SCLC) with response to systemic chemotherapy, based on two randomized clinical trials, which varied in patient selection and radiation therapy doses administered. The current pattern of practice among US radiation oncologists is unknown. MATERIALS AND METHODS: We have surveyed practicing US radiation oncologist via a short online questionnaire. Respondents' characteristics and their self-rated knowledge base were analyzed for association with their treatment recommendations. RESULTS: We received 473 responses from practicing US radiation oncologists. Over half of respondents were practicing for over 10 years after completing residency training and 70% treated more than 10 lung cancer patients per year. 96% of respondents recommend TCRT for patients with ES-SCLC after systemic chemotherapy. Patient selection and radiation therapy doses vary greatly. High self-rated knowledge of individual clinical trials is associated with lower TCRT recommended doses. Patients treated at academic centers are less likely to receive TCRT than patients treated in private clinics (p=0.0101). CONCLUSION: Our analysis revealed that among the respondents, there was a very high adherence to current NCCN guidelines, which recommend TCRT for ES-SCLC patients with clinical response to systemic chemotherapy. The great variability in patient selection and radiation therapy doses is concerning and calls for future clinical trials to standardize treatment approaches and improve treatment outcomes among patients with ES-SCLC. Until such data exists and in light of poor long-term survival of patients with ES-SCLC, the shorter and less toxic regimen of 30Gy in 10 fractions should be used as the standard of care and the more aggressive regimens studied on clinical protocols.

Current Patterns of Care for Patients with Extensive-Stage SCLC: Survey of U.S. Radiation Oncologists on Their Recommendations Regarding Prophylactic Cranial Irradiation.

INTRODUCTION: Conflicting data from randomized clinical trials incite the debate over the appropriate use of prophylactic cranial irradiation (PCI) for patients with extensive-stage SCLC (ES-SCLC) who achieve clinical response to systemic chemotherapy. The current pattern of practice among U.S. radiation oncologists is unknown. METHODS: We surveyed practicing U.S. radiation oncologists through a short online questionnaire. Respondents' characteristics and their self-rated knowledge base were analyzed for association with their treatment recommendations. RESULTS: We received 473 responses from practicing U.S. radiation oncologists. More than half of the respondents had been practicing for more than 10 years after completing residency training, and 70% had treated more than 10 patients with lung cancer per year. Of the respondents, 90% recommended brain magnetic resonance imaging (MRI) before initiation of PCI and 98% recommended PCI for patients with ES-SCLC after systemic chemotherapy. Half of the respondents followed their patients with brain MRI after completion of PCI. One-third of the respondents prescribed memantine to patients undergoing PCI. Among the respondents, recent graduates (p = 0.004) and physicians practicing in academic centers (p = 0.005) were more likely to prescribe memantine. Self-rated knowledge base was not associated with any treatment recommendations. CONCLUSIONS: Our analysis revealed that among the respondents, there was a very high adherence to current National Comprehensive Cancer Network guidelines, which recommend providing universal PCI and obtaining brain MRI before initiation of PCI for patients with ES-SCLC with clinical response to systemic chemotherapy. These guidelines and practice patterns are not supported by clinical evidence because patients in the European Organization for Research and Treatment of Cancer trial did not undergo brain MRI before PCI and the Japanese randomized trial has shown a possible detrimental effect of PCI on overall survival when brain MRI was incorporated. A critical reevaluation of current guidelines is essential to determine the appropriate management of these patients.

Transurethral surgery and twice-daily radiation plus paclitaxel-cisplatin or fluorouracil-cisplatin with selective bladder preservation and adjuvant chemotherapy for patients with muscle invasive bladder cancer (RTOG 0233): a randomised multicentre phase 2 trial.

BACKGROUND: We assessed effectiveness, safety, and tolerability of paclitaxel or fluorouracil when added to radiation plus cisplatin followed by adjuvant chemotherapy in a programme of selected bladder preservation for patients with muscle invasive bladder cancer. METHODS: In our randomised phase 2 trial, we enrolled patients with T2-4a transitional cell carcinoma of the bladder at 24 medical centres in the USA. We randomly allocated patients to receive paclitaxel plus cisplatin (paclitaxel group) or fluorouracil plus cisplatin (fluorouracil group) with twice-daily radiation in random block sizes per site on the basis of clinical T-stage (T2 vs T3-4). Patients and physicians were aware of treatment assignment. All patients had transurethral resection of bladder tumour and twice-daily radiotherapy to 40·3 Gy, along with allocated chemotherapy, followed by cystoscopic and biopsy assessment of response. Patients who had a tumour response with downstaging to T0, Tcis, or Ta received consolidation chemoradiotherapy to 64·3 Gy, with the same chemotherapy regimen as in the induction phase. Patients received adjuvant cisplatin-gemcitabine-paclitaxel after the end of chemoradiotherapy. If, after induction, persistent disease was graded as T1 or worse, we recommended patients undergo cystectomy and adjuvant chemotherapy. We assessed the primary endpoints of rates of treatment completion and toxic effects in all randomly allocated patients. This study is registered with ClinicalTrials.gov, number NCT00055601. FINDINGS: Between Dec 13, 2002, and Jan 11, 2008, we enrolled 97 patients, of whom 93 were eligible for analysis. Median follow-up was 5·0 years (IQR 5·0-6·2). Of 46 patients in the paclitaxel group, 45 (98%) completed induction (16 [35%] with grade 3-4 toxicity), 39 (85%) completed induction and consolidation (11 [24%] with grade 3-4 toxicity due to consolidation), and 31 (67%) completed the entire protocol with adjuvant chemotherapy. 34 (85%) of 40 assessable patients in the paclitaxel group had grade 3-4 toxicity during adjuvant chemotherapy. Of 47 patients in the fluorouracil group, 45 (96%) completed induction (nine [19%] with grade 3-4 toxicity), 39 (83%) completed induction and consolidation (12 [26%] had grade 3-4 toxicity due to consolidation), and 25 (53%) completed the entire protocol with adjuvant chemotherapy. 31 (76%) of 41 assessable patients in the fluorouracil group had grade 3-4 toxicity during adjuvant chemotherapy. Five (11%) patients treated with the paclitaxel regimen and three (6%) patients treated with the fluorouracil regimen developed late grade 3-4 radiotherapy toxicities. 11 (24%) patients treated with the paclitaxel regimen and 16 (34%) patients treated with the fluorouracil regimen developed late grade 3-4 toxicities unrelated to radiotherapy. One patient (in the fluorouracil group) died during follow-up. Six (13%) patients in the paclitaxel group and in three (6%) patients in the fluorouracil group discontinued due to treatment-related toxicity. INTERPRETATION: In the absence of phase 3 data, our findings could inform selection of a bladder-sparing trimodality chemotherapy regimen for patients with muscle invasive bladder cancer. FUNDING: US National Cancer Institute.