Stereotactic Radiation for Ultra-Central Non-Small Cell Lung Cancer: A Safety and Efficacy Trial (SUNSET).

PURPOSE: The use of stereotactic body radiation therapy for tumors in close proximity to the central mediastinal structures has been associated with a high risk of toxicity. This study (NCT03306680) aimed to determine the maximally tolerated dose of stereotactic body radiation therapy for ultracentral non-small cell lung carcinoma, using a time-to-event continual reassessment methodology. METHODS AND MATERIALS: Patients with T1-3N0M0 (≤6 cm) non-small cell lung carcinoma were eligible. The maximally tolerated dose was defined as the dose of radiation therapy associated with a ≤30% rate of grade (G) 3 to 5 prespecified treatment-related toxicity occurring within 2 years of treatment. The starting dose level was 60 Gy in 8 daily fractions. The dose-maximum hotspot was limited to 120% and within the planning tumor volume; tumors with endobronchial invasion were excluded. This primary analysis occurred 2 years after completion of accrual. RESULTS: Between March 2018 and April 2021, 30 patients were enrolled at 5 institutions. The median age was 73 years (range, 65-87) and 17 (57%) were female. Planning tumor volume was abutting proximal bronchial tree in 19 (63%), esophagus 5 (17%), pulmonary vein 1 (3.3%), and pulmonary artery 14 (47%). All patients received 60 Gy in 8 fractions. The median follow-up was 37 months (range, 8.9-51). Two patients (6.7%) experienced G3-5 adverse events related to treatment: 1 patient with G3 dyspnea and 1 G5 pneumonia. The latter had computed tomography findings consistent with a background of interstitial lung disease. Three-year overall survival was 72.5% (95% CI, 52.3%-85.3%), progression-free survival 66.1% (95% CI, 46.1%-80.2%), local control 89.6% (95% CI, 71.2%-96.5%), regional control 96.4% (95% CI, 77.2%-99.5%), and distant control 85.9% (95% CI, 66.7%-94.5%). Quality-of-life scores declined numerically over time, but the decreases were not clinically or statistically significant. CONCLUSIONS: Sixty Gy in 8 fractions, planned and delivered with only a moderate hotspot, has a favorable adverse event rate within the prespecified acceptability criteria and results in excellent control for ultracentral tumors.

Incorporation of Functional Lung Imaging Into Radiation Therapy Planning in Patients With Lung Cancer: A Systematic Review and Meta-Analysis.

Our purpose was to provide an understanding of current functional lung imaging (FLI) techniques and their potential to improve dosimetry and outcomes for patients with lung cancer receiving radiation therapy (RT). Excerpta Medica dataBASE (EMBASE), PubMed, and Cochrane Library were searched from 1990 until April 2023. Articles were included if they reported on FLI in one of: techniques, incorporation into RT planning for lung cancer, or quantification of RT-related outcomes for patients with lung cancer. Studies involving all RT modalities, including stereotactic body RT and particle therapy, were included. Meta-analyses were conducted to investigate differences in dose-function parameters between anatomic and functional RT planning techniques, as well as to investigate correlations of dose-function parameters with grade 2+ radiation pneumonitis (RP). One hundred seventy-eight studies were included in the narrative synthesis. We report on FLI modalities, dose-response quantification, functional lung (FL) definitions, FL avoidance techniques, and correlations between FL irradiation and toxicity. Meta-analysis results show that FL avoidance planning gives statistically significant absolute reductions of 3.22% to the fraction of well-ventilated lung receiving 20 Gy or more, 3.52% to the fraction of well-perfused lung receiving 20 Gy or more, 1.3 Gy to the mean dose to the well-ventilated lung, and 2.41 Gy to the mean dose to the well-perfused lung. Increases in the threshold value for defining FL are associated with decreases in functional parameters. For intensity modulated RT and volumetric modulated arc therapy, avoidance planning results in a 13% rate of grade 2+ RP, which is reduced compared with results from conventional planning cohorts. A trend of increased predictive ability for grade 2+ RP was seen in models using FL information but was not statistically significant. FLI shows promise as a method to spare FL during thoracic RT, but interventional trials related to FL avoidance planning are sparse. Such trials are critical to understanding the effect of FL avoidance planning on toxicity reduction and patient outcomes.

Are we ready for deintensification in human papillomavirus-positive oropharyngeal carcinomas?

PURPOSE OF REVIEW: Excellent outcomes following contemporary treatment of human papillomavirus (HPV)-positive oropharyngeal carcinoma (HPV+ OPC) have prompted the exploration of deintensification approaches to minimize treatment-related toxicities. This review describes the landscape of deintensification to date (up to November 2022). RECENT FINDINGS: Although several deintensification trials have been published, none are practice changing. Three phase III randomized-controlled trials studying cetuximab and radiation therapy vs. standard chemoradiotherapy all showed inferior outcomes. Although some phase II trials reported favourable outcomes, they are often single-arm trials without an adequate control arm, thereby limiting the ability to modify practice. SUMMARY: Substantial effort has been expended to explore deintensification options for selected HPV+ OPC patients aiming to avoid unnecessary toxicity. Strategies have included replacing cisplatin with cetuximab, reduced chemotherapy or radiotherapy intensity, reduction of radiotherapy volumes and risk stratification after trans-oral surgery or following induction chemotherapy. Challenges remain in the current deintensification landscape, including identifying the most suitable candidates along with a choice of most appropriate deintensification strategies. Promising selection criteria included either static baseline features or kinetic characteristics of clinical-biological parameters. Practice-changing trials remain elusive, and the search continues to attempt optimization of the therapeutic ratio for these patients.

Locoregional recurrence after cystectomy in muscle invasive bladder cancer: Implications for adjuvant radiotherapy.

PURPOSE: We report the patterns of locoregional recurrence (LRR) in muscle invasive bladder cancer (MIBC), and propose a risk stratification to predict LRR for optimizing the indication for adjuvant radiotherapy. MATERIALS AND METHODS: The study included patients of urothelial MIBC who underwent radical cystectomy with standard perioperative chemotherapy between 2013 and 2019. Recurrences were classified into local and/or cystectomy bed, regional, systemic, or mixed. For risk stratification modelling, T stage (T2, T3, T4), N stage (N0, N1/2, N3) and lymphovascular invasion (LVI positive or negative) were given differential weightage for each patient. The cohort was divided into low risk (LR), intermediate risk (IR) and high risk (HR) groups based on the cumulative score. RESULTS: Of the 317 patients screened, 188 were eligible for the study. Seventy patients (37.2%) received neoadjuvant chemotherapy (NACT) while 128 patients (68.1%) had T3/4 disease and 66 patients (35.1%) had N+ disease. Of the 55 patients (29%) who had a recurrence, 31 (16%) patients had a component of LRR (4% cystectomy bed, 11.5% regional 0.5% locoregional). The median time to LRR was 8.2 (IQR 3.3-18.8) months. The LR, IR and HR groups for LRR based on T, N and LVI had a cumulative incidence of 7.1%, 21.6%, and 35% LRR, respectively. The HR group was defined as T3, N3, LVI positive; T4 N1/2, LVI positive; and T4, N3, any LVI. The odds ratio for LRR was 3.37 (95% CI 1.16-9.73, P = 0.02) and 5.27 (95% CI 1.87-14.84, P = 0.002) for IR and HR respectively, with LR as reference. CONCLUSION: LRR is a significant problem post radical cystectomy with a cumulative incidence of 35% in the HR group. The proposed risk stratification model in our study can guide in tailoring adjuvant radiotherapy in MIBC.

Outcomes of locally advanced cervical cancer presenting with obstructive uropathy: An institutional audit.

BACKGROUND: There is paucity of outcome data of patients with cervical cancer presenting with malignant obstructive uropathy. The present retrospective study describes outcomes of patients with cervical cancer who presented with obstructive uropathy at the time of diagnosis and underwent urinary diversion with percutaneous nephrostomy (PCN) before/during treatment. METHODS: Patients who underwent PCN from January 2010 to June 2015 were included. Intent of treatment (radical or palliative) was decided within multidisciplinary team depending on disease stage, Karnofsky performance status (KPS), and degree of renal derangement. Treatment and outcome details were retrieved from electronic records. Time to normalization of creatinine, feasibility of delivering planned treatment, and overall survival (OS) were determined. Impact of various prognostic factors on outcomes was determined using univariate or multivariate analysis. RESULTS: After PCN and double-J stenting, 50% were eligible for (chemo) radiation. All radically treated patients (26/52) received brachytherapy. The median EQD2 to point A was 78 Gy (72-84 Gy). The median OS was 10 (0.5-60) months. Patients who completed chemoradiation had median OS of 31 months. Those receiving radical radiation and palliative radiation had median OS of 11 and 6 months, respectively. On univariate analysis, smaller tumor size (p = 0.03), high KPS (P = 0.04), and radical intent of treatment (P = 0.05) predicted for OS. CONCLUSION: Patients presenting with obstructive uropathy have median OS less than a year despite urinary diversion. Select cohort with good performance status, small tumor size, and serum creatinine of ≤3 mg/dL may be selected for diversion procedures and potential radical treatment.