A. Juloori

Evolving Paradigm of Radiotherapy for High-Risk Prostate Cancer: Current Consensus and Continuing Controversies

High-risk prostate cancer is an aggressive form of the disease with an increased risk of distant metastasis and subsequent mortality. Multiple randomized trials have established that the combination of radiation therapy and long-term androgen deprivation therapy improves overall survival compared to either treatment alone. Standard of care for men with high-risk prostate cancer in the modern setting is dose-escalated radiotherapy along with 2-3 years of androgen deprivation therapy (ADT). There are research efforts directed towards assessing the efficacy of shorter ADT duration. Current research has been focused on assessing hypofractionated and stereotactic body radiation therapy (SBRT) techniques. Ongoing randomized trials will help assess the utility of pelvic lymph node irradiation. Research is also focused on multimodality therapy with addition of a brachytherapy boost to external beam radiation to help improve outcomes in men with high-risk prostate cancer.

Incidence and predictors of severe acute esophagitis and subsequent esophageal stricture in patients treated with accelerated hyperfractionated chemoradiation for limited-stage small cell lung cancer

PURPOSE Clinical and dosimetric predictors of severe (grade 3 or greater) acute esophageal toxicity and subsequent esophageal dilation were explored in patients with limited-stage small cell lung cancer treated with accelerated hyperfractionated chemoradiation. METHODS AND MATERIALS A total of 130 patients were identified who were treated to 45 Gy in 1.5-Gy twice-daily fractions with concurrent platinum-based chemotherapy between 2000 and 2009. Data on clinical, disease-related, and treatment-related variables were collected. Patients with percutaneous endoscopic gastrostomy tube insertion or intravenous hydration because of poor oral intake were designated as having acute grade 3 esophagitis. Univariate and multivariate analyses that associated treatment characteristics with esophagitis were assessed via logistic regression, and optimal cut points were identified with recursive partitioning analysis. RESULTS Twenty-five patients developed severe acute esophagitis, at a rate of 26% (18/69) in patients treated with earlier 3-dimensional conformal radiation therapy techniques and 11.5% (7/61) in patients treated with intensity modulated radiation therapy techniques and omission of elective nodal irradiation. The incidence of esophageal stricture was 6% overall (8 of 128 eligible) but 26% (6/23) among those who experienced prior grade 3 acute esophagitis and 2% (2/105) among those with acute esophagitis less than or equal to grade 2. Significant multivariate predictors of acute esophagitis were mean dose and volume of esophagus receiving at least 5% to 35% of the prescribed dose (V5 to V40). Patients with V5 ≥ 74% had a 44.4% risk of severe acute esophagitis (12/27) versus 12.6% (13/103) among those with V5 < 74%. V45 was the only dosimetric predictor for esophageal stricture, with 13.7% of patients in whom V45 was ≥37.5% requiring subsequent dilation. CONCLUSIONS Modern radiation techniques are associated with a lower frequency of severe acute esophagitis than previous paradigms. The proportion of esophagus receiving low- to moderate-range doses (mean, V5 through V40) predicts acute esophagitis, whereas the proportion of esophagus that receives high doses (V45) predicts the development of esophageal stricture that requires dilation. Patients who develop grade 3 acute esophagitis are at significant risk for subsequent esophageal stricture, whereas those with acute esophagitis of grade 2 or less display minimal risk.

The risk of radiation necrosis following stereotactic radiosurgery with concurrent systemic therapies

To investigate late toxicity among patients with newly-diagnosed brain metastases undergoing stereotactic radiosurgery (SRS) with concurrent systemic therapies with or without whole-brain radiation therapy (WBRT). Patients with newly-diagnosed brain metastasis who underwent SRS at a single tertiary-care institution from 1997 to 2015 were eligible for inclusion. The class and timing of all systemic therapies were collected for each patient. The primary outcome was the cumulative incidence of radiographic radiation necrosis (RN). Multivariable competing risks regression was used to adjust for confounding. During the study period, 1650 patients presented with 2843 intracranial metastases. Among these, 445 patients (27%) were treated with SRS and concurrent systemic therapy. Radiographic RN developed following treatment of 222 (8%) lesions, 120 (54%) of which were symptomatic. The 12-month cumulative incidences of RN among lesions treated with and without concurrent therapies were 6.6 and 5.3%, respectively (p = 0.14). Concurrent systemic therapy was associated with a significantly increased rate of RN among lesions treated with upfront SRS and WBRT (8.7 vs. 3.7%, p = 0.04). In particular, concurrent targeted therapies significantly increased the 12-month cumulative incidence of RN (8.8 vs. 5.3%, p < 0.01). Among these therapies, significantly increased rates of RN were observed with VEGFR tyrosine kinase inhibitors (TKIs) (14.3 vs. 6.6%, p = 0.04) and EGFR TKIs (15.6 vs. 6.0%, p = 0.04). Most classes of systemic therapies may be safely delivered concurrently with SRS in the management of newly-diagnosed brain metastases. However, the rate of radiographic RN is significantly increased with the addition of concurrent systemic therapies to SRS and WBRT.

Factors Associated With Acute and Chronic Wound Complications in Patients With Soft Tissue Sarcoma With Long-term Follow-up

Objectives: To identify the rates of acute and chronic wound complications and factors associated in a cohort of patients treated for soft tissue sarcoma (STS) with modern radiotherapy (RT) and surgical techniques. Materials and Methods: An Institutional Review Board–approved database was used to identify all adult nonmetastatic patients treated for STS at a single institution between 2006 and 2015 with a minimum follow-up of 1 year. Factors associated with acute and chronic wound complications were analyzed using binomial logistic regression including interaction terms. Results: In all, 271 patients were identified with a median follow-up of 3.2 years. The rate of acute wound complications was 22.1%. On univariate analysis, trunk versus extremity location (P<0.001), radiation therapy (P=0.04), and preoperative therapy (P=0.03) were associated with acute wound complications and a trend was noted for reconstruction (P=0.07). On multivariate analysis, extremity tumors were associated with a higher rate of acute wound complications compared with trunk tumors without RT (P=0.02). Utilization of RT was associated with increased risk for extremity tumors (P=0.07). The rate of chronic wound complications was 3.3%. Radiation was associated with increased chronic wound complications (P=0.03) and trends were noted for trunk versus extremity location (P=0.08) and a history of acute wound complications (P=0.12). Conclusions: Several factors associated with acute and chronic wound complications were identified in STS patients including timing of RT, tumor site, and reconstruction use. The development of acute wound complications may also be associated with an increased risk of chronic wound complications.

Local control for clinical stage I non-small cell lung cancer treated with 5-fraction stereotactic body radiation therapy is not associated with treatment schedule

PURPOSE Clinical concern remains regarding the relationship between consecutive (QD) versus nonconsecutive (QoD) lung stereotactic body radiation therapy (SBRT) treatment schedules and outcomes for clinical stage I non-small cell lung cancer (NSCLC). We examined a multi-institutional series of patients receiving 5-fraction lung SBRT to compare the local failure rates and overall survival between patients receiving QD versus QoD treatment. METHODS AND MATERIALS Lung SBRT databases from 2 high-volume institutions were combined, and patients receiving 5-fraction SBRT for a solitary stage I NSCLC were identified. QD treatment was defined as completing SBRT in ≤7 days, whereas QoD treatment was defined as completing treatment in >7 days. To control for patient characteristics between the 2 institutions, a 1:1 propensity-matched analysis was performed. Multivariable logistic regression was performed to identify variables independently associated with local failure, and Cox proportional hazards modeling to identify variables independently associated with increased mortality. RESULTS From 2005 through 2016, 245 clinical stage I NSCLC patients receiving 5-fraction SBRT were identified. A total of 117 (47.8%) patients received QD treatment and 128 (52.2%) patients received QoD treatment. On propensity-matched analysis, no association was seen between QD treatment and local failure (odds ratio [OR] for QD treatment, 0.48; 95% confidence interval [CI], 0.12-1.99; P = .5). On multivariable logistic regression, central tumors were independently associated with increased likelihood of local recurrence (OR, 5.2; 95% CI, 1.11-24.2; P = .04). Kaplan-Meier analysis identified no difference in median overall survival between QD versus QoD treatments (38.0 vs 38.0 months, log-rank P = .7), respectively. QD treatment was not associated with an increased mortality hazard (hazard ratio, 1.08; 95% CI, 0.67-1.75; P = .75). CONCLUSIONS This analysis demonstrated no association between QD versus QoD treatment scheduling and local control or overall survival for early-stage NSCLC.

Effect of Switching Systemic Treatment After Stereotactic Radiosurgery for Oligoprogressive, Metastatic Renal Cell Carcinoma

Background We assessed the clinical outcomes of patients with oligoprogressive renal cell carcinoma (mRCC) treated with stereotactic radiosurgery (SRS), stratified by changing or continuing systemic treatment. Patients and Methods Ninety‐five consecutive patients with clear cell mRCC who had undergone SRS to the central nervous system (CNS) or spine during systemic treatment were divided into 3 cohorts: those who continued the same systemic therapy (STAY), those who changed systemic treatment after SRS (SWITCH), and patients with progression outside the SRS sites, who also changed systemic treatment (PD‐SYS). The primary outcome was treatment duration after SRS, defined as the interval between SRS and discontinuation of the current systemic therapy for the STAY group and discontinuation of the first subsequent therapy in the SWITCH and PD‐SYS groups. Results Local control with SRS was achieved in 85% of the patients. The most common systemic treatment at SRS included anti–vascular endothelial growth factor (67%), mammalian target of rapamycin (14%), and programmed cell death protein 1 inhibitors (9%). The median treatment duration for the STAY group was 5.2 months (95% confidence interval [CI], 3.5‐6.9) compared with 5.0 months (95% CI, 4.3‐5.7) for the SWITCH group (P = .549) and 3.1 months (95% CI, 1.7‐4.5) for the PD‐SYS group (P = .07, compared with all other patients). No difference in median overall survival was found for the STAY and SWITCH groups (24.2 vs. 27.1 months; P = .381) but was significantly longer than that for the PD‐SYS group (P = .025). Conclusion The decision to continue the same systemic therapy at SRS to treat CNS or spinal lesions did not compromise the clinical outcomes of patients with oligoprogressive mRCC. Micro‐Abstract Stereotactic radiosurgery (SRS) can be used to treat metastatic renal cell carcinoma (mRCC) when progression involves a limited number of metastases. In the present retrospective study of consecutive patients with oligoprogressive mRCC, the decision to continue with the same systemic therapy after SRS did not compromise treatment duration or overall survival. Medical treatment decisions should be individualized according to tolerance of the existing regimen, progressive disease outside sites of SRS, and patient access to subsequent therapies.

Definitive chemoradiation in locally advanced squamous cell carcinoma of the hypopharynx: Long-term outcomes and toxicity

Background/Aim: Definitive chemoradiation (CRT) is a common approach for locally advanced hypopharyngeal squamous cell carcinoma (SCC) with the goal of organ preservation. Reports on long-term oncologic and functional outcomes have been limited. This study reports on outcomes utilizing this approach at a single institution over 30 years. Materials and Methods: Medical records for patients with stage III-IVB SCC of the hypopharynx were retrospectively reviewed. Patient and disease-related factors were identified and analyzed for impact on overall survival (OS), cancer-specific survival (CSS), disease-free survival, distant failure, and locoregional failure. Results: A total of 54 patients were identified who were treated with definitive CRT to a mean dose of 72 Gy. With a median follow-up period of 49.8 months, 5- and 10-year OS was 62% and 43% respectively. Five and 10-year CSS were 74% and 72% respectively. Ten-year local control was 78%. Of the 37 patients with no treatment failure, 29% experienced a grade 3 or higher late toxicity, with the majority resolving during continued long-term follow-up. Conclusion: This study demonstrates good outcomes with long-term follow-up with acceptable rates of late toxicities. The findings here represent the longest published median follow-up in this population and validate the strategy of organ preservation.