D.P. Bergsma

Bladder cancer in the elderly patient: challenges and solutions

Bladder cancer (BC) is an age-associated malignancy with increased prevalence in the elderly population. Elderly patients are a vulnerable population at increased risk for treatment-related toxicity secondary to medical comorbidities and geriatric syndromes. As a result, this population has been historically undertreated and suffers worse disease-specific outcomes than younger patients with BC. Recognition of this disparity has led to efforts to individualize treatment decisions based on functional status rather than chronologic age in an effort to optimize the use of curative therapies for the fit elderly and modify treatments to reduce the risk of toxicity and disease-related morbidity in vulnerable or frail patients. The comprehensive geriatric assessment is a decision framework that helps to balance underlying health considerations and risks of therapy with aggressiveness of the cancer. Development of systemic therapies with increased efficacy against BC and reduced toxicity are eagerly awaited, as are techniques and interventions to reduce the morbidity from surgery and radiation for patients with BC.

Radiotherapy for Oligometastatic Lung Cancer

Non-small cell lung cancer (NSCLC) typically presents at an advanced stage, which is often felt to be incurable, and such patients are usually treated with a palliative approach. Accumulating retrospective and prospective clinical evidence, including a recently completed randomized trial, support the existence of an oligometastatic disease state wherein select individuals with advanced NSCLC may experience historically unprecedented prolonged survival with aggressive local treatments, consisting of radiotherapy and/or surgery, to limited sites of metastatic disease. This is reflected in the most recent AJCC staging subcategorizing metastatic disease into intra-thoracic (M1a), a single extra thoracic site (M1b), and more diffuse metastases (M1c). In the field of radiation oncology, recent technological advances have allowed for the delivery of very high, potentially ablative, doses of radiotherapy to both intra- and extra-cranial disease sites, referred to as stereotactic radiosurgery and stereotactic body radiotherapy (or SABR), in much shorter time periods compared to conventional radiation and with minimal associated toxicity. At the same time, significant improvements in systemic therapy, including platinum-based doublet chemotherapy, molecular agents targeting oncogene-addicted NSCLC, and immunotherapy in the form of checkpoint inhibitors, have led to improved control of micro-metastatic disease and extended survival sparking newfound interest in combining these agents with ablative local therapies to provide additive, and in the case of radiation and immunotherapy, potentially synergistic, effects in order to further improve progression-free and overall survival. Currently, despite the tantalizing potential associated with aggressive local therapy in the setting of oligometastatic NSCLC, well-designed prospective randomized controlled trials sufficiently powered to detect and measure the possible added benefit afforded by this approach are desperately needed.

A population-based study of prognosis and survival in patients with second primary thyroid cancer after Hodgkin lymphoma

Abstract Hodgkin lymphoma (HL) survivors are at increased risk of thyroid cancer (TC). We sought to determine whether increased risks of high-risk pathology or mortality are seen with thyroid cancer after HL (HL-TC) compared with first primary thyroid cancer (TC-1). From the Surveillance, Epidemiology and End Results (SEER) registry, we compared patient and tumor characteristics as well as survival outcomes between HL-TC and TC-1 and fit a multivariable Cox model to assess for a possible association between HL history and overall survival after TC. Among 139,297u2009TC-1 and 174u2009HL-TC patients, history of HL was not associated with anaplastic or sarcoma TC. Multivariable analyzes showed that history of HL was not associated with a difference in risk of death after TC (hazard ratio: 0.96, 95% confidence interval: (0.81, 1.13), pu2009=u2009.61). Despite a significantly increased risk of TC among HL survivors, prior HL is not associated with more aggressive pathologic subtypes or worse prognosis.

Local control rates with five fractions of stereotactic body radiotherapy for primary lung tumors: a single institution experience of 153 consecutive patients

Background: We report our institutional experience with stereotactic body radiotherapy (SBRT) for treatment of non-small cell lung cancer (NSCLC). Methods: One hundred and fifty-three consecutive patients diagnosed with NSCLC were treated with image-guided SBRT between 2008 and 2012. Stage I patients were treated in lieu of resection, stage II-III patients were not candidates for concurrent chemoradiation and had disease amenable to SBRT and stage IV patients had oligometastatic disease. The median prescribed isocenter dose was 50 Gy in five fractions (range, 40-60 Gy) with the majority (n=121) receiving 50 Gy in five fractions. The 80% isodose line covered the planning target volume (PTV) [defined as gross tumor volume (GTV) + 7-11 mm volumetric expansion). Follow-up ranged from 1-46 months with a median of 13 months. Results: The 1- and 2-year local control (LC) rates for all patients were 92% and 85% respectively. For 111 patients with stage I NSCLC, 1- and 2-year LC was 95% and 85%, with all local recurrence (LR) occurring within 2 years. LC at 1- and 2-year was 87% for both stage II (n=19) and stage III (n=14), with all LR occurring within 10 months. For oligometastatic stage IV (n=9) patients, LC at 1- and 2-year was 71%, with all LR occurring within 5 months. Two-year LC among patients with tumors 1 cm. Tumor histology, prescribed dose, patient age, and prior radiotherapy (RT) or surgery had no significant impact on LC rates. Prior chemotherapy had a significant negative impact on LC with 1- and 2-year LC of 59%, compared to 1- and 2-year LC of 93% and 85%, respectively (P=0.015). n multivariate analysis, stage was the only significant predictor of LC. Among stage I NSCLC patients, 6 of 111 developed LR, 13 developed distant failures (of whom 5 also developed LR). Of these 111 patients, 5 died from NSCLC and 2 died from causes other than NSCLC; no patient died from treatment-related toxicity. Conclusions: SBRT plays a vital role and offers excellent LC in medically-inoperable NSCLC patients, with treatment during the early stage of the disease determined as the single most significant predictor of LC on multivariate analysis.

The evolving role of radiotherapy in treatment of oligometastatic NSCLC

Non-small cell lung cancer (NSCLC) patients with metastases limited in site and number, termed oligometastases, may represent a unique subpopulation of advanced NSCLC with improved prognosis. The optimal management of these patients remains unclear with the treatment approach currently undergoing a paradigm shift. The potential benefit of aggressive metastasis directed local treatment with surgery and/or radiotherapy (RT) in combination with systemic therapy is bolstered predominantly by retrospective analyses but also by a growing number of non-randomized prospective studies regarding the use of ablative RT techniques including stereotactic body radiotherapy (SBRT), alternatively termed stereotactic ablative radiotherapy (SABR), directed at the primary tumor (if present) and all metastatic sites. Long-term survival is possible in a subset of patients treated aggressively in this manner. The challenge for the clinical oncology community moving forward is appropriately selecting patients for this treatment approach based on clinical, imaging, and molecular features and increasing enrollment of patients to prospective clinical trials to more definitively determine the added benefit and appropriate timing of aggressive metastasis directed therapy in the oligometastatic setting.

Single-Fraction Radiosurgery Using Conservative Doses for Brain Metastases: Durable Responses in Select Primaries With Limited Toxicity

BACKGROUNDnOptimal doses for single-fraction stereotactic radiosurgery (SRS) in the treatment of brain metastases are not well established. Our institution utilized conservative dosing compared to maximum-tolerated doses from the Radiation Therapy Oncology Group 90-05 Phase I study.nnnOBJECTIVEnTo report individual lesion control (LC) from conservative single-fraction doses and determine factors affecting LC.nnnMETHODSnFrom 2003 to 2015, patients who underwent linear accelerator-based single-fraction SRS for cerebral/cerebellar metastases and receiving at least 1 follow-up magnetic resonance imaging (MRI) were identified. Lesion response was assessed by a size-based rating system and modified Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria.nnnRESULTSnAmong 188 patients with 519 lesions, median survival was 13.1 mo; median follow-up time with MRI was 9.6 mo per course. Median tumor-periphery dose was 15 Gy (range: 7.5-20.7). Median lesion volume was 0.5 cc and diameter was 9 mm (range: 2-45). Concordance between RANO-BM and size-based system was 93%. Crude 1-yr LC was 80%, 73%, 56%, and 38% for lesions 1 to 10, 11 to 20, 21 to 30, >31 mm, respectively. On multivariate analysis, increased size, melanoma and colorectal histology, and progression after whole brain radiation therapy predicted worse LC. When excluding lesions treated as a boost, dose was a significant predictor of LC in multivariate models (hazard ratio 0.89, P = .01). Symptomatic radiation necrosis occurred in 10 lesions in 10 patients.nnnCONCLUSIONnHistology predicts LC after conservative SRS doses with evidence of a dose-response relationship. Conservative single-fraction SRS doses confer minimal toxicity and acceptable control in certain subgroups (breast cancer, <5 mm), with suboptimal control in larger lesions and in combination with whole brain radiation therapy.

Long-Term Survival of a Patient with Metastatic Small-Cell Carcinoma of the Stomach Treated with Radiation Therapy

Small-cell carcinoma (SCC), or high-grade neuroendocrine carcinoma of the stomach, is a rare subtype of extra-pulmonary SCC which is almost invariably lethal. Gastric SCC often presents with local symptoms indistinguishable from other primary stomach cancers; however, both regional and distant spread are common at the initial presentation. Depending on symptoms and patient performance status, treatment typically consists of chemotherapy or resection followed by adjuvant chemotherapy, as even patients with limited stage gastric SCC likely have micrometastatic disease at the time of diagnosis. In this case report, we describe the long-term survival of a 75-year-old male with recurrent oligometastatic high-grade neuroendocrine carcinoma of the stomach treated with radiation therapy (RT) alone. He presented with abdominal pain and dyspepsia and was found to have a 6 cm locally invasive node-positive gastric SCC initially treated with extensive surgical resection. He was not a candidate for adjuvant chemotherapy, and surveillance imaging subsequently confirmed metachronous liver and local recurrences within 1 year after surgery, which were managed with stereotactic body RT and conventional radiation, respectively. An additional para-aortic nodal recurrence was treated with intensity-modulated radiotherapy 7 years after surgery with good response. He tolerated all RT courses without notable radiation-related toxicity and remains in complete remission 11 years after initial diagnosis.