N. Sen

Role of Chemoradiotherapy in the Adjuvant and Neoadjuvant Settings for Resectable Pancreatic Cancer

Pancreatic cancer is the 10th most commonly diagnosed malignancy in the USA and the fourth most common cause of cancer-related death. Worldwide, the mortality incidence ratio approaches 98%. Although only 15-20% of patients present with resectable disease, there is international consensus that complete surgical resection (R0, i.e. grossly and microscopically negative margins) is a vital part of any curative treatment paradigm. Despite advances in surgical technique, peri-operative care, chemotherapy and radiation delivery techniques over the past two decades, 5 year overall survival rates for resected pancreatic cancer with modern therapies remain around 20-25%. There is level I evidence for adjuvant chemotherapy in fully resected pancreatic cancer, but randomised trials examining the role of adjuvant chemoradiotherapy to date do not provide clear support for radiation therapy in this setting. In addition, efforts to increase the proportion of long-term survivors have recently centred on increasing the resectability of locoregional disease by incorporating neoadjuvant treatment before definitive surgery. Post-hoc analysis of randomised data as well as retrospective reviews have shown that there are several independent prognostic factors that may have considerable impact on survival outcomes, complicating interpretation and comparison of historical data. There is considerable interest in adjuvant and neoadjuvant therapy, but there is significant controversy as to whether radiation is of value, especially in the adjuvant context. Herein, we explore the sources of those controversies.

Survival Benefit of Surgery after Chemoradiotherapy for Stage III (N0–2) Non-Small-Cell Lung Cancer Is Dependent on Pathologic Nodal Response

Introduction: The benefit of surgery (trimodality therapy [TMT]) after chemoradiotherapy (CRT) for patients with stage III non–small-cell lung cancer (NSCLC) is controversial, but nodal pathologic complete response (N-PCR) is accepted as a strong predictor of overall survival (OS). We compared the outcomes of patients treated with TMT versus CRT, focusing on the importance of N-PCR. Methods: Patients with stage III NSCLC treated with CRT or TMT from December 2004 through December 2012 were included; patients with N3 disease were excluded. Pathologic nodal response dichotomized surgical patients into N-PCR versus residual nodal disease (RND) groups. Actuarial OS, progression-free survival (PFS), and distant metastasis-free survival (DMFS) were compared between patients treated with CRT and TMT and between CRT and N-PCR/RND. Results: The cohort was composed of 138 patients (52% CRT and 48% TMT). The median OS was significantly higher after TMT than after CRT (81 versus 31.8 mo, p = 0.0068). This benefit was restricted to N-PCR (n = 50, 83.2 versus 31.8 mo, p = 0.0004), as RND (n = 19) experienced poor OS (16.1 mo). On multivariable analyses, N-PCR had superior OS (hazard ratio [HR], 0.38; p = 0.0012), PFS (HR, 0.42; p = 0.0005), and DMFS (HR, 0.42; p = 0.0007) compared with CRT. Conversely, there were trends for worse OS and PFS for RND versus CRT, although only inferior DMFS was significant (HR, 1.83; p = 0.04). Conclusions: Surgical patients with complete nodal clearance experienced superior survival, but those with RND fared no better than CRT alone. Mediastinal response may play an important role in the decision to proceed with surgical resection after CRT for stage III NSCLC.

Lung stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer in the very elderly (≥80 years old): Extremely safe and effective

OBJECTIVE Stereotactic body radiotherapy (SBRT) for early-stage non-small-cell lung cancer (NSCLC) is the standard of care in medically inoperable patients. In very elderly patients, previous studies have shown SBRT to offer excellent local control, though with higher toxicities than in younger populations. We report our institutional experience using SBRT in the definitive management of NSCLC in patients ≥80years old. MATERIALS AND METHODS Using an IRB-approved registry of 158 patients treated with definitive-intent lung SBRT for early-stage NSCLC at our institution between 2010 and 2016, 31 consecutively treated patients ≥80years of age were identified. CTCAEv4 scales were prospectively recorded during follow-ups and utilized for toxicity assessments. Kaplan-Meier estimates were utilized for survival analyses. RESULTS For the 31 patients (with 34 lesions) included, median age was 83 (R: 80-93), median ECOG performance status was 2 (R: 0-3), and median follow-up was 15.8months (R: 3.1-48.3). Median PTV size was 24.0cm3 (R: 5.83-62.1cm3). Median prescription dose was 54Gy in 3 fractions (R: 50-60Gy in 3-8 fractions). Local control was 100% at 1year and 92.3% at 2years. Median survival was 29.1months. There were no grade 2-5 toxicities. Grade 1 toxicities included: fatigue in 5 patients (16.1%), asymptomatic (radiographic) pneumonitis in 12 (38.7%), and dyspnea in 2 (6.5%). CONCLUSIONS Lung SBRT with a BED of ≥100Gy10 for very elderly patients with NSCLC is extremely safe and effective, with inordinately low toxicity rates (zero grade 2-5 toxicities). With stringent dosimetric parameters and planning guidelines, patients ≥80years remain excellent candidates for full-dose SBRT. SUMMARY SBRT for early-stage NSCLC is the accepted standard of care in medically inoperable patients, though in many very elderly patients, dose is either de-intensified or withheld for concern of toxicity in the setting of advanced age and competing risks. In this study of our very elderly (≥80years old) early-stage NSCLC patients, we highlight both the extremely high efficacy and tolerability (zero grade 2 or above toxicities) associated with definitive intent SBRT.

Advances in Radiation Therapy for Primary and Metastatic Adult Soft Tissue Sarcomas

Soft tissue sarcomas (STS) consist of a heterogeneous group of rare malignancies arising from mesenchymal origin. While surgical resection is the primary treatment for STS, the use of radiotherapy (RT) as an adjunctive modality has been shown to improve oncologic outcomes. Technologic improvements, such as image guidance and intensity-modulated radiotherapy that significantly improve both the precision and delivery of RT, have led to the reduction of long-term RT toxicities without compromising outcomes. This review addresses these technologic advancements as well as discussing the most current updates regarding the use of brachytherapy, charged particles, and novel agents with RT.

Truebeam Radiosurgery for the Treatment of Trigeminal Neuralgia: Preliminary Results at a Single Institution

Introduction Radiosurgery is now an established method of satisfactory pain control in patients with trigeminal neuralgia (TN). The Varian Truebeam STx (Varian Medical Systems, Palo Alto, CA) linear accelerator (LINAC) system is an arc-based, frameless stereotactic radiosurgery system used for the treatment of TN. To our knowledge, there has been only one published series of patient histories that documents the use of a frameless LINAC system for the treatment of TN. We describe the treatment parameters, patient outcomes, and complications associated with the treatment of TN. Methods All patients treated with the Truebeam system for TN between 2012 and 2015, with at least a six-month follow-up, were identified. A dose of 90 Gy was delivered to the isocenter using a 0.5 cm diameter cone. The cisternal segment of the trigeminal nerve was placed at the location of the LINAC isocenter using an ExacTrac™ (Brainlab, Munich, Germany) image guidance system. The radiosurgical dose, Barrow Neurologic Institute pain score (BNI PS), symptom recurrence, magnetic resonance imaging (MRI) radiographic changes, and other complications, including Barrow Neurologic Institute facial numbness score (BNI FN), were analyzed. Results A total of 18 patients—15 women and 3 men—with a mean age of 58 years (median: 59 years; range: 22-84 years) were treated at our institution. Fourteen patients (78%) had a BNI PS of IIIb or better, which was considered successful treatment. Twelve patients had excellent (BNI PS I) pain relief and two patients had good (BNI PS II-IIIB; recurrence after one year) pain relief. The pain of four patients recurred after a mean of 10 months. Conclusion Truebeam radiosurgery can provide effective and safe treatment for patients suffering from TN. The efficacy appears similar to other frame- and frameless-based systems

Clinical features and outcomes in young adults with oral tongue cancer in young adults

OBJECTIVE To evaluate outcomes and survival in young patients with oral tongue cancer (OTC). METHODS Retrospective chart review of patients aged 18-40 with OTC treated between 2000 and 2016. Tumor characteristics of p16 expression, perineural invasion (PNI), and lymph-vascular invasion (LVI) were evaluated. Recurrence-free (RFS) and overall survival (OS) data were analyzed according to Kaplan-Meier method with univariate analysis. RESULTS A total of 23 patients were identified: 12 with early stage disease (ESD, stage I), and 11 with advanced stage disease (ASD, stage III or IV), (17 men and 6 women). Mean age at presentation was 34.5 years (±5 months) and mean follow-up was 46.6 months. For all patients, 5-year RFS was 62% and OS 66%. RFS for ESD was 73% and ASD 25% (log rank p = 0.011). OS for ESD was 100% and ASD 55% (log rank p = 0.012). 22% indicated tobacco use >5 pack-years and 9% heavy alcohol use. Factors associated with worse OS were neck disease (log rank p = 0.073), positive margins (log rank p = 0.001), and LVI (log rank p = 0.002). Factors associated with worse RFS were chemotherapy or radiation therapy prior to surgery (log rank p = 0.002), neck disease (log rank p = 0.047), positive margins (log rank p = 0.039), and PNI (log rank p = 0.001). Expression of p16 was observed in five cases and was not significantly associated with OS or RFS. CONCLUSION In young patients with OTC, factors associated with worse outcomes are similar to known predictors in older patients. Expression of p16 was not statistically associated with improved OS. OS in patients with ESD was excellent (100%), and significantly worse for ASD.

Initial clinical experience using a novel pd-103 surface applicator for the treatment of retroperitoneal and abdominal wall malignancies

Definitive surgical resection is an integral component of curative intent management for localized soft tissue sarcoma, and margin status is a strong predictor for recurrence. Because of the large size and intimate association of retroperitoneal soft tissue sarcoma with vital normal structures at presentation, microscopically positive margins are common after curative intent interventions. This reality has driven clinical interest in the incorporation of radiation therapy (RT) in the intraoperative context, and several series have demonstrated promising rates of local control using intraoperative electron beam RT (IOERT). Similar principles may apply to the radical treatment of abdominal malignancies with soft tissue invasion. IOERT has been used for the treatment of locally advanced and recurrent colon cancer with promising rates of local control. Recently, an innovative, unidirectional, Pd-103 lowdose-rate brachytherapy device, CivaSheet (CivaTech, Durham, NC), has been developed for clinical use as an intraoperative RT (IORT) alternative. Here we present our initial clinical experience with the first 2 cases using this new IORT technology to boost the tumor bed after preoperative RT, including device implantation at time of tumor resection and evaluation of its positional stability with postimplant computed tomography (CT) studies.

Role of Radiation Therapy

Patients with pancreatic cancer present in one of three ways. They may be clearly resectable, not clearly resectable but without evidence of hepatic, peritoneal, or more distant dissemination, or with obvious disseminated disease. While the majority of patients do have metastatic disease (>50–60 %) and the minority with clearly resectable disease is small (10–20 %), the 30–40 % of patients who are not clearly metastatic and not clearly resectable provide special challenges and opportunities in management. In this last category, a number of factors have been recognized as important for prognostic and therapeutic decision making. These include the distinction between “borderline resectable” and more locally advanced presentations, clinical factors (performance status, anemia, weight loss), biologic factors (SMAD 4, TP53), and the impact on survival of achieving gross total resection when clinically appropriate and possible. In addition, technical advances in radiation oncology provide new opportunities for safely exploiting this expanding base of clinical and prognostic knowledge for patient benefit. These issues are reviewed with an eye toward helping the busy surgeon or medical oncologist optimize care and outcomes for their pancreatic cancer patients in this category.