Delphi consensus on stereotactic ablative radiotherapy for oligometastatic and oligoprogressive renal cell carcinoma-a European Society for Radiotherapy and Oncology study endorsed by the European Association of Urology.

The purpose of this European Society for Radiotherapy and Oncology (ESTRO) project, endorsed by the European Association of Urology, is to explore expert opinion on the management of patients with oligometastatic and oligoprogressive renal cell carcinoma by means of stereotactic ablative radiotherapy (SABR) on extracranial metastases, with the aim of developing consensus recommendations for patient selection, treatment doses, and concurrent systemic therapy. A questionnaire on SABR in oligometastatic renal cell carcinoma was prepared by a core group and reviewed by a panel of ten prominent experts in the field. The Delphi consensus methodology was applied, sending three rounds of questionnaires to clinicians identified as key opinion leaders in the field. At the end of the third round, participants were able to find consensus on eight of the 37 questions. Specifically, panellists agreed to apply no restrictions regarding age (25 [100%) of 25) and primary renal cell carcinoma histology (23 [92%] of 25) for SABR candidates, on the upper threshold of three lesions to offer ablative treatment in patients with oligoprogression, and on the concomitant administration of immune checkpoint inhibitor. SABR was indicated as the treatment modality of choice for renal cell carcinoma bone oligometatasis (20 [80%] of 25) and for adrenal oligometastases 22 (88%). No consensus or major agreement was reached regarding the appropriate schedule, but the majority of the poll (54%-58%) retained the every-other-day schedule as the optimal choice for all the investigated sites. The current ESTRO Delphi consensus might provide useful direction for the application of SABR in oligometastatic renal cell carcinoma and highlight the key areas of ongoing debate, perhaps directing future research efforts to close knowledge gaps.

5-year outcomes after stereotactic ablative body radiotherapy for primary renal cell carcinoma: an individual patient data meta-analysis from IROCK (the International Radiosurgery Consortium of the Kidney).

BACKGROUND: Stereotactic ablative body radiotherapy (SABR) is a non-invasive treatment option for primary renal cell carcinoma, for which long-term data are awaited. The primary aim of this study was to report on long-term efficacy and safety of SABR for localised renal cell carcinoma. METHODS: This study was an individual patient data meta-analysis, for which patients undergoing SABR for primary renal cell carcinoma across 12 institutions in five countries (Australia, Canada, Germany, Japan, and the USA) were eligible. Eligible patients had at least 2 years of follow-up, were aged 18 years or older, had any performance status, and had no previous local therapy. Patients with metastatic renal cell carcinoma or upper-tract urothelial carcinoma were excluded. SABR was delivered as a single or multiple fractions of greater than 5 Gy. The primary endpoint was investigator-assessed local failure per the Response Evaluation Criteria in Solid Tumours version 1.1, and was evaluated using cumulative incidence functions. FINDINGS: 190 patients received SABR between March 23, 2007, and Sept 20, 2018. Single-fraction SABR was delivered in 81 (43%) patients and multifraction SABR was delivered in 109 (57%) patients. Median follow-up was 5·0 years (IQR 3·4-6·8). 139 (73%) patients were men, and 51 (27%) were women. Median age was 73·6 years (IQR 66·2-82·0). Median tumour diameter was 4·0 cm (IQR 2·8-4·9). 96 (75%) of 128 patients with available operability details were deemed inoperable by the referring urologist. 56 (29%) of 190 patients had a solitary kidney. Median baseline estimated glomerular filtration rate (eGFR) was 60·0 mL/min per 1·73 m2 (IQR 42·0-76·0) and decreased by 14·2 mL/min per 1·73 m2 (IQR 5·4-22·5) by 5 years post-SABR. Seven (4%) patients required dialysis post-SABR. The cumulative incidence of local failure at 5 years was 5·5% (95% CI 2·8-9·5) overall, with single-fraction SABR yielding fewer local failures than multifraction (Gray's p=0·020). There were no grade 3 toxic effects or treatment-related deaths. One (1%) patient developed an acute grade 4 duodenal ulcer and late grade 4 gastritis. INTERPRETATION: SABR is effective and safe in the long term for patients with primary renal cell carcinoma. Single-fraction SABR might yield less local failure than multifraction, but further evidence from randomised trials is needed to elucidate optimal treatment schedules. These mature data lend further support for renal SABR as a treatment option for patients unwilling or unfit to undergo surgery. FUNDING: None.

Immune checkpoint-mediated myositis and myasthenia gravis: A case report and review of evaluation and management.

BACKGROUND: We present a case of myositis and possible overlapping neuromuscular junction disorder following treatment with nivolumab for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). METHODS: We report a 75-year-old man with recurrent stage IVA, T1N2cM0 oral cavity HNSCC treated with weight-dosed nivolumab who presented three weeks later with severe fatigue, generalized weakness, and bilateral ptosis. Evaluation demonstrated elevated creatine kinase and myopathic motor units on electromyography, supporting a diagnosis of an underlying muscle disease. Elevated serum acetylcholine receptor binding antibodies raised the possibility of concurrent myasthenia gravis. RESULTS: He received corticosteroids and plasmapheresis without improvement in muscle weakness. His course was complicated by bacteremia, cardiac arrest, and concerns for recurrent malignancy. Following a two-month hospital stay, he was made comfort care and died. CONCLUSIONS: With increasing usage of checkpoint inhibitors in HNSCC, clinicians must be aware of and vigilant for associated rare but serious adverse events.

Local therapy for triple-negative breast cancer: a comprehensive review.

Owing to its aggressive course, triple-negative breast cancer remains an important clinical issue of current interest compared with hormone-receptor positive subtypes. Recent research has focused on determining the optimal local therapy (breast conversation therapy vs mastectomy) for this cancer subtype. In this overview, we examine outcomes based on immunohistochemistry, gene expression profiles, type of local therapy and in the era of neoadjuvant chemotherapy. Based on multiple observational reports risk for locoregional recurrence appears to be similar to reported outcomes in other subtypes. However, distant recurrence continues to be a significant concern for triple-negative breast cancer, indicating the need for better systemic therapies. To date, insufficient evidence exists to determine whether breast conserving therapy or mastectomy results in superior outcomes.

Pretreatment and Posttreatment Tumor Metabolic Activity Assessed by FDG-PET/CT as Predictors of Tumor Recurrence and Survival Outcomes in Early-Stage Non-Small Cell Lung Cancer Treated With Stereotactic Body Radiation Therapy.

Purpose: Stereotactic body radiation therapy (SBRT) is considered the standard of care for medically inoperable early-stage non-small cell lung cancer. There is mixed evidence on the prognostic significance of tumor metabolic activity assessed by positron emission tomography combined with computed tomography (PET/CT) using F-18 fluorodeoxyglucose (FDG). The objectives of this study were to evaluate the maximum standardized uptake value (SUVmax) pretreatment and at 3 and 6 months after SBRT for prediction of tumor control and survival outcomes. Methods and Materials: Consecutive patients from a single institution with T12N0M0 non-small cell lung cancer receiving primary treatment with SBRT with pretreatment FDG-PET/CT (n = 163) and follow-up FDG-PET/CT at 3 or 6 months (n = 71) were included. Receiver operator characteristic analysis was performed to dichotomize variables for Kaplan-Meier survival analysis. Multivariate analysis was performed with Cox proportional hazards regression. Results: Median follow-up was 19 months. For the whole cohort, 1-year and 2-year local control, progression-free survival (PFS), and overall survival (OS) were 95.0% and 80.3%, 87.1% and 75.4%, and 67.0% and 49.6% respectively. The following pre-SBRT SUVmax cutoffs were significant: SUV > 4.0 for distant failure-free survival (adjusted hazard ratio [aHR], 3.33, P = .006), >12.3 for PFS (aHR, 2.80, P = .011), and >12.6 for OS (aHR, 3.00, P = .003). SUVmax decreases of at least 45% at 3 months (aHR, 0.15, P = .018), and 53% at 6 months (aHR, 0.12, P = .046) were associated with improved local failure-free survival. Conclusions: Pre-SBRT SUVmax cutoffs can predict distant failure, PFS, and OS. At both 3 and 6 months after SBRT, cutoffs for percentage change in SUVmax can potentially stratify risk of local recurrence.

A Comparative Study of Patients With Early-Stage Non-Small Cell Lung Cancer Treated With Stereotactic Body Radiation Therapy Using CyberKnife and Linear Accelerator-Based Volumetric Modulated Arc Therapy.

PURPOSE: Stereotactic body radiation therapy (SBRT) has become the standard of care for medically inoperable early-stage non-small cell lung cancer. We investigated 2 modalities of lung SBRT, CyberKnife (CK) and volumetric modulated arc therapy (VMAT), for differences in dosimetric parameters, tumor control, and clinical outcomes. METHODS AND MATERIALS: Patients who underwent SBRT for T1-2N0M0 non-small cell lung cancer from 2012 to 2018 were included. Dosimetric parameters for target volume coverage and organ-at-risk dose distribution were collected. Survival outcomes were evaluated using the Kaplan-Meier method with log-rank test. A multivariate Cox proportional hazards model was analyzed for local, regional, and distant tumor control; overall survival (OS) and progression-free survival; and radiation pneumonitis. RESULTS: Two hundred twenty-seven patients (142 CK, 85 VMAT SBRT) met inclusion criteria. Overall, the local, regional, and distant control rates were 89.3%, 86.3%, and 87.4% at 2 years, and the OS was 67.5% and 32.8% at 2 and 5 years, respectively. VMAT delivered higher maximum doses to the gross tumor volume and planning target volume and had a lower lung and heart V5. Although there was no difference in local or distant failure, progression-free survival, or OS, VMAT was associated with superior freedom from regional failure (adjusted hazard ratio, 0.26; P = .045). With no difference between treatment modalities, 11.9% of patients developed grade 1 to 2 radiation pneumonitis. There were no grade 3+ events of radiation pneumonitis. CONCLUSIONS: This study revealed that VMAT and CK provided comparable local and distant control and survival outcomes; however, VMAT exhibited better regional control. Further study in this regard is imperative.

Pattern of Radiotherapy Treatment in Low-Risk, Intermediate-Risk, and High-Risk Prostate Cancer Patients: Analysis of National Cancer Database.

Background: In this study, the utilization rates and survival outcomes of different radiotherapy techniques are compared in prostate cancer (PCa) patients stratified by risk group. Methods: We analyzed an extensive data set of N0, M0, non-surgical PCa patients diagnosed between 2004 and 2015 from the National Cancer Database (NCDB). Patients were grouped into six categories based on RT modality: an intensity-modulated radiation therapy (IMRT) group with brachytherapy (BT) boost, IMRT with/without IMRT boost, proton therapy, stereotactic body radiation therapy (SBRT), low-dose-rate brachytherapy (BT LDR), and high-dose-rate brachytherapy (BT HDR). Patients were also stratified by the National Comprehensive Cancer Network (NCCN) guidelines: low-risk (clinical stage T1−T2a, Gleason Score (GS) ≤ 6, and Prostate-Specific Antigen (PSA) < 10), intermediate-risk (clinical stage T2b or T2c, GS of 7, or PSA of 10−20), and high-risk (clinical stage T3−T4, or GS of 8−10, or PSA > 20). Overall survival (OS) probability was determined using a Kaplan−Meier estimator. Univariate and multivariate analyses were performed by risk group for the six treatment modalities. Results: The most utilized treatment modality for all PCa patients was IMRT (53.1%). Over the years, a steady increase in SBRT utilization was observed, whereas BT HDR usage declined. IMRT-treated patient groups exhibited relatively lower survival probability in all risk categories. A slightly better survival probability was observed for the proton therapy group. Hormonal therapy was used for a large number of patients in all risk groups. Conclusion: This study revealed that IMRT was the most common treatment modality for PCa patients. Brachytherapy, SBRT, and IMRT+BT exhibited similar survival rates, whereas proton showed slightly better overall survival across the three risk groups. However, analysis of the demographics indicates that these differences are at least in part due to selection bias.

Final results of a dose escalation protocol of stereotactic body radiotherapy for poor surgical candidates with localized renal cell carcinoma.

BACKGROUND AND PURPOSE: We previously demonstrated the safety of doses up to 48 Gy in 4 fractions with stereotactic body radiotherapy (SBRT) in poor surgical candidates with localized renal cell carcinoma (RCC). In an additional expansion cohort, we aimed to assess the safety of further dose escalation to 48-60 Gy in 3 fractions. MATERIAL AND METHODS: Patients were required to have localized RCC and be poor surgical candidates due to medical comorbidities. Dose-limiting toxicity (DLT) was defined as acute (<180 days) grade ≥3 gastrointestinal/genitourinary toxicity by CTCAEv4. Tumor response was assessed using RECIST 1.1 criteria measurements every 6 months for 3 years and optional percutaneous biopsy. RESULTS: Groups of 4, 4, and 3 patients received 48, 54, and 60 Gy in 3 fractions, respectively from 2012 to 2016. Median follow-up was 34.3 months. Zero DLTs were observed. Acute toxicities were limited to grade 1 fatigue and nausea in 45.5% and 18.1%. Late grade 2+ and grade 3+ possibly treatment-related events occurred in 18.1% and 9.1%, respectively. Three-year local control was 90% by RECIST 1.1 criteria. Five of 5 post-treatment biopsies in the expansion cohort were positive by Hematoxylin and Eosin staining. Three of the 5 patients with positive biopsies have been observed for 1.2-3.9 years without evidence of progression. CONCLUSION: Dose escalation to 60 Gy in 3 fractions was achieved without DLTs. Favorable local control rates were observed, and the interpretation of post-SBRT biopsies remains uncertain. Further studies comparing SBRT to percutaneous ablation for poor surgical candidates with RCC are warranted.

The changing landscape of stage III lung cancer: a literature review.

INTRODUCTION: The treatment of stage III non-small cell lung cancer (NSCLC) remains challenging and associated with overall poor outcomes. Since seminal studies in the early 90s introduced concurrent chemo-radiotherapy as standard of care for treatment of this disease, no major advances have been introduced in this landscape. Both radiation dose escalation and neoadjuvant/adjuvant chemotherapy strategies were unsuccessful to improve the survival over standard of care radiation dose and chemotherapy schedule: five-year overall survival (OS) ranging from 15-20%. However, in 2017 the PACIFIC Trial demonstrated that the addition of consolidative immune checkpoint inhibitor durvalumab for 1 year led to superior progression-free survival (PFS) and 3-year overall survival with no significant increase in toxicity compared to placebo in patients who achieved disease control with concurrent chemo-RT. AREAS COVERED: This article reviews the treatment evolution of stage III NSCLC over the past decades, discusses current standard of care strategies, and highlights potential future directions for the management of this condition. EXPERT OPINION: Ongoing trials incorporating upfront checkpoint inhibitors with radiotherapy will answer whether adding checkpoint inhibitors to chemotherapy or substituting them for chemotherapy altogether will improve long-term outcome.

Institutional practices of withholding enteral feeding from intubated patients.

OBJECTIVE: This study compared the practices of anesthesia, anesthesia critical care, surgical critical care, and medical critical care departments that have training programs for the length of time they withhold enteral feeding from intubated patients before seven scheduled procedures: 1) extubation; 2) tracheostomy; 3) abdominal surgery; 4) nonabdominal surgery; 5) magnetic resonance imaging or computerized tomography; or placing the patient in the 6) Trendelenberg or 7) prone position. DESIGN: One-time survey of 297 anesthesia and critical care training programs in the United States. MEASUREMENTS AND MAIN RESULTS: Eighty programs responded (27%). We compared the median hours of withholding enteral feeding of intubated patients according to training program type for each of the procedures. None of the programs withheld enteral feeds from intubated patients scheduled for magnetic resonance imaging/computerized tomography scans, nor for the Trendelenberg position (median = 0 hour). A significant difference among program types was found for extubation, with anesthesia departments having significantly longer times (median = 6 hours) compared with anesthesia critical care (median = 4 hours), surgical critical care (median = 2 hours), and medical critical care (1.5 hours) departments (chi = 8.77, df = 3, p = 0.032). For scheduled tracheostomy, surgical critical care departments reported shorter times (median = 4 hours) than did all other surveyed departments (median = 6 hours) (chi = 7.28, df = 3, p = 0.063). CONCLUSIONS: Differences in opinion exist among specialty training programs about the length of time necessary for withholding enteral feeding from intubated patients before scheduled procedures, especially extubation and tracheostomy. To resolve physician conflicts and to best serve these patients, best practice guidelines for withholding enteral feeding from intubated patients before scheduled procedures need to be developed jointly by the critical care specialties.

Spinal Cord Neuromodulation Therapy for Levofloxacin-Reinduced Complex Regional Pain Syndrome and Neurotoxicity: A Case Report.

Fluoroquinolones are a class of popular outpatient antimicrobial agents with a wide spectrum of therapeutic indications for respiratory and genitourinary infections. Though the most common side effects are gastrointestinal, fluoroquinolones have been increasingly associated with neurotoxicity including peripheral neuropathy and seizures. We present here a case of a 43-year-old woman with previously resolved type I complex regional pain syndrome (CRPS) who presented with symptoms of CRPS and neurotoxicity in the setting of levofloxacin administration. Our aim is to advocate for increased caution in prescribing to patients with a history of neuropathology including CRPS.

Topical Sphenopalatine Ganglion Block Compared With Epidural Blood Patch for Postdural Puncture Headache Management in Postpartum Patients: A Retrospective Review.

BACKGROUND AND OBJECTIVES: Postdural puncture headache (PDPH) is a severe and debilitating complication of unintentional dural puncture. The criterion-standard treatment for PDPH has been epidural blood patch (EBP), but it is an invasive intervention with the potential for severe complications, such as meningitis and paralysis. We believe this is the first ever 17-year retrospective chart review in which we compare the effectiveness of sphenopalatine ganglion block (SPGB) to EBP for PDPH treatment in postpartum patients. METHODS: We conducted a chart review of the first authors' obstetric patients who experienced PDPH from an unintentional dural puncture from a 17-gauge Tuohy needle for labor epidural from January 1997 to July 2014. Demographic characteristics, headache severity, and associated symptoms were collected prior to treatment. Forty-two patients who received SPGB and 39 patients who received EBP were identified. Residual headache, recovery from associated symptoms, and new treatment complications were compared between the 2 groups at 30 minutes, 1 hour, 24 hours, 48 hours, and 1 week posttreatment. RESULTS: A greater number of patients showed significant relief in their PDPH and associated symptoms at 30 and 60 minutes after treatment with SPGB than after treatment with EBP (P < 0.01). Only the EBP patients complained of posttreatment complications, which all resolved in 48 hours. CONCLUSIONS: A greater number of patients experienced a quicker onset of headache relief, without any new complications, from treatment with SPGB versus EBP. We believe that SPGB is a safe, inexpensive, and well-tolerated treatment. We hope that clinical trials will be conducted in the future that will confirm our findings and allow us to recommend SPGB for PDPH treatment prior to offering patients EBP.

Participation in and impact of a depression care management program targeting low-income minority patients in an urban community-based clinic.

BACKGROUND: African American people experience disproportionately higher rates of chronic depression, and among those affected, the condition is less likely to be detected and treated than in non-Hispanic white people. OBJECTIVE: To address this disparity in our primary care clinic, we introduced a validated framework for detecting and managing depression. METHODS: Over a 5-year period, there were 146 patients diagnosed as having depression and enrolled in a depression care management program. We evaluated the feasibility and effectiveness of that program using baseline and follow-up screening data from the Patient Health Questionnaire-9. RESULTS: The mean baseline severity score of 20.60 was reduced to 15.89 at 6 months (P < 0.001) and to 16.62 at 12 months. Patients achieved their best score, a mean of 12.93, 10.14 months after baseline (P < 0.001). The last mean severity score, after 15.47 months, was 14.60, a significant difference compared with baseline (P < 0.001). Although baseline severity scores for both groups were similar (P = 0.534), patients who remained engaged with the program demonstrated better scores and achieved greater severity score reductions from baseline to the last measure (P < 0.001). This study did not find any differences between the sexes when comparing PHQ-9 scores at baseline (P = 0.074), 6 months (P = 0.303), and 12 months (P = 0.429) and best (P = 0.875) and last (P = 0.640) scores. CONCLUSIONS: Most of the improvement was witnessed in the first 10 months of treatment. Patients with more medical comorbidities participated longer in the study than patients with fewer comorbidities. Further research could elicit the relationship between improvement in mental health and medical conditions.