Durable Local Control Research Articles

Prospective Assessment of Proton Therapy for Malignant Pleural Mesothelioma

Radiation therapy (RT) treatment for malignant pleural mesothelioma (MPM) is challenging due to the large treatment fields needed for both definitive and adjuvant RT following extrapleural pneumonectomy or lung-sparing surgery. Most published experiences to date report photon and electron outcomes. Proton therapy (PT) can offer substantial dose sparing to the lungs and other organs, which may improve the therapeutic ratio. Reports of PT for MPM are limited. We report our experience treating patients with MPM with definitive or adjuvant PT. We hypothesized that PT would achieve high local control with low pneumonitis and esophagitis rates. We reviewed all consecutive patients treated for MPM at our institution between 2011-2017 as part of a prospective registry study. We assessed disease control outcomes and CTCAEv4 acute and late toxicities. Nineteen patients treated to 21 PT courses were included. Patients were predominantly male (74%) and Caucasian (100%), with epithelioid (84%) histology and stage III-IV disease (89%). The median age at PT start was 68.4 years delivered at a median of 15.4 mo. (range 3.5-59.4 mo.) after MPM diagnosis. Most patients received pemetrexed and cisplatin or carboplatin prior to (n = 15) or during (n = 2) PT. Two patients received concurrent pemetrexed alone, and 1 received concurrent pembrolizumab (IT). PT was delivered as adjuvant treatment after lung-sparing extended pleurectomy decortication (n = 8), for gross progression on/after systemic therapy (n = 12), or as primary definitive concurrent therapy (n = 1). Median PT dose was 54 CGE in 2.0 CGE daily fractions (range, 50-75/1.8-2.6 CGE). At a median follow-up of 17.7 months after start of PT, local, regional, and distant control were 90%, 48%, and 14%, respectively. The median progression-free survival and overall survival (OS) were 5.1 months (95% CI 3.3-10.7 months) and 17.7 months (95% CI 7.2-30.4 months) from start of PT, respectively. The 6-, 12-, 18-, and 24- month OS rates were 84%, 68%, 47%, and 37%, respectively. Grade ≥3 toxicities included a bronchopleural fistula (n = 1, late, G4) and dyspnea (n = 1, acute, G3). Acute grade 2 toxicities included RT dermatitis (n = 8), dysphagia/esophagitis (n = 5), anorexia (n = 5), fatigue (n = 4), cough (n = 2), and dyspnea (n = 1). Late grade 2 toxicities included RT pneumonitis (n = 4, including 1 that received concurrent IT and 1 that received post-RT IT with a history of autoimmune disease). ECOG PS remained stable from before to after PT (mean 0.81 to 0.90). In the largest prospective registry experience of PT for MPM to date, PT achieved durable local control with toxicity that compares favorably with prior photon experiences. Thus, PT may offer safer integration of RT in multi-modality paradigms for MPM. Additional follow-up, patients, and study with IT agents are needed to further establish the long-term survival and toxicity profile of PT for MPM.

Stereotactic Body Radiation Therapy (SBRT) in Pelvic Lymph Node Oligometastases

The role of stereotactic body radiation therapy (SBRT) in achieving durable local control and palliation of pain in pelvic lymph node oligometastatic disease is not well-studied. We performed a retrospective analysis of 30 patients with 43 pelvic lymph node oligometastases from various primary cancers all but one with non-prostate primaries treated at our institution with SBRT. The median follow-up time was 21 months. The median SBRT dose was 24 Gy in four fractions. The one-, two-, and five-year local control was 74%, 71%, and 70% and one-, two-, and five-year overall survival was 70%, 47%, and 31%. Toxicities were mild with no grade 3 or higher.

Developing an Algorithm to Identify Palliative Radiation Treatments: A Single-Institution 10-year Experience

The definition of palliative radiotherapy (RT) has been changing over the past 20 years as patients live longer and radiotherapy for durable local control is delivered more frequently, even in the setting of metastatic disease. As such, the role of palliative RT continues to expand with changing and emerging treatment paradigms. The University of Pennsylvania established a dedicated palliative RT service in 2012 and has delivered several thousand courses of palliative RT over the last 11 years. In spite of a checkbox for “curative” or “palliative” intent, these courses are not always clearly defined in our treatment planning software. The development of a database of patients treated with palliative RT will allow us to study trends in approach and the algorithm may help other institutions to similarly study patients treated with palliative radiation. We sought to design a large, single-institution retrospective database of patients treated with palliative RT using an algorithmic approach to define and capture such patients based on clinical and electronic medical record data. All non-pediatric RT courses delivered at the University of Pennsylvania from 2008-2019 were eligible for review. Clinical details available for each course from the Varian Aria database (Varian Medical Systems, Palo Alto, CA) were course number, course name, provider name, treatment modality (proton vs. photon), treatment intent (provider specified as palliative vs. curative, and often left blank), associated ICD diagnosis code, prescribed dose, number of initial fractions, and number of cone down fractions. We pre-specified a target 95% sensitivity for identifying non-curative courses to include in the database. We defined palliative RT as any course delivered with non-curative intent including any ablative courses for oligometastatic disease, treatment for recurrent disease, or dose-escalated courses for durable local control. Investigators initially reviewed 214 courses delivered in January 2017 and based on chart review identified which courses were administered with curative versus palliative intent. This was repeated for courses delivered in March and April 2017. In total 634 courses were initially classified. We developed initial rules to reflect treatment parameters indicating an RT course was definitely curative (18 rules), definitely palliative (21), likely curative (12), or likely palliative (6). These rules were run on additional months as test data sets and adjusted to yield a higher sensitivity in identifying non-curative courses. Crude analyses were then iteratively run to determine which order and combination of rules led to best sensitivity in identifying palliative courses compared to gold standard of manual review of each treatment course. Our algorithm parses treatment courses in the following stepwise fashion: 1) Exclude courses delivered for benign conditions indicated by diagnosis code 2) Isolate all courses indicated by physician as “palliative” intent and add to database. Based on chart review “curative” was not a reliable indicator of curative intent as we have defined it. 3) From remaining courses isolate all courses with course names including “liver” and “SBRT” (stereotactic body radiotherapy) lung for manual review. The intent of these courses could not be reliably determined from available clinical details. 4) From remaining, exclude all courses with 1 or more “definitely curative” indicators and 0 “definitely palliative” indicators. 5) From remaining, isolate all courses with 1 or more “definitely palliative” and 0 or 1 “definitely curative” indicators and include in database. 6) From remaining, compare sum of “likely palliative” indicators and if greater than sum of “likely curative” indicators, include in database. With this basic approach we screened 23,782 courses and according to the stepwise process above found 1) 5,301 palliative courses, 2) 2,415 requiring manual review, 3) 13,467 excluded as definitely curative, 4) 2,195 definitely palliative, and 5) 404 likely palliative. In sum 7,900 palliative courses would be included in the database, with potentially more after manual review of 2,415 courses of liver-directed RT or lung SBRT. We were able to use a small number of relevant clinical details to reliably classify a majority of RT courses as curative or non-curative in intent. In the evolving setting of oligometastatic/oligorecurrent/oligoprogressive disease, identification of which RT courses are “curative” is highly variable between providers. Manual review of RT courses and rule generation results in >95% identification of palliative RT courses, but we have yet to show if machine learning techniques can improve on our manually generated algorithm.

Gamma Knife Boost for Head and Neck Cancers with Skull Base Extension: A Case Series

Many Head and Neck Cancers (HNC) have a predilection for perineural spread which can track proximally and lead to skull base involvement. In cases of skull base involvement, including gross/residual disease after surgery, it can be challenging to deliver tumoricidal radiotherapy dose without exceeding nearby critical structure constraints despite the adoption of highly conformal approaches such as IMRT and proton. The use of GammaKnife stereotactic radiosurgery as a boost (GK-boost) to IMRT may further improve sparing of these critical structures while escalating dose to disease in the skull base. In this case series we report the clinical outcomes of patients receiving a GK-boost to the skull base as a component of their overall IMRT plan. Patients with HNC and gross/residual skull base disease after surgery treated with conventionally fractionated radiation therapy (IMRT/IMPT) plus a GK-boost between March 2014 and September 2019 were retrospectively reviewed. Five patients had squamous cell carcinomas (SCC) from a skin primary, one patient had a SCC of the oral cavity, and one patient had an adenoid cystic carcinoma. Treatment toxicity, survival, and local control were evaluated. Of the patients evaluated, 4 received adjuvant radiotherapy after surgery and 3 were treated with definitive radiotherapy. The median dose for IMRT was 66 Gy in 30-33 Fx. The median GK-boost dose was 8-11 Gy in a single fraction. The majority of patients received the GK boost after a median interval of 9 days post IMRT. The boost was delivered to the trigeminal nerve tract in five patients and the facial nerve tract in two patients. Median follow-up was 33 months. There were no local failures. There was 1 death and 1 regional recurrence in the same patient. This patient had a regional recurrence 11.2 months after completing treatment in the left orbit outside the prescribed PTV, which received 30 Gy or less. There were no G3 or higher acute toxicity associated with GK boost. There were 2 patients that developed asymptomatic temporal lobe radionecrosis. GammaKnife boost to the skull base is well tolerated and provides a durable local control benefit. An ongoing dosimetric comparative study will assess the extent of normal tissue dose sparing. A larger prospective study is needed to validate these clinical findings.

Long-Term Results of Partial Breast Irradiation After Breast-Conserving Surgery for Early Stage Breast Cancer: A Prospective Phase II Trial in China.

BackgroundPartial breast radiotherapy (PBI) has emerged as an option after breast-conserving surgery for early stage breast cancer patients.MethodsA total of 55 patients with early stage breast cancer between 2009 and 2013 were enrolled in this single-institutional phase II prospective clinical trial. All patients received adjuvant PBI-IMRT after lumpectomy, with the prescription of 48 Gy in 12 fractions at 4 Gy per fraction, 5 days a week. The primary endpoint was ipsilateral breast tumor recurrence (IBTR), the other endpoints were a regional nodal failure (RNF), distant metastasis (DM) rate, disease-free survival (DFS), and overall survival (OS). These endpoints were used to evaluate clinical outcomes. The cosmetic effects and the late toxicity were assessed according to Harvard standard scale and CTCAE 3.0, respectively.ResultsIn our cohorts, the median age was 45.60 years old (range 31–65 years) and 29.09% of these patients were post-menopause (n = 16). Most patients were T1 stage (65.45%) or N0 stage (70.91%). 80% of patients were ER-positive, 67.27% PR positive, and 61.82% HER2 negative. At the median follow-up of 9.25 years, RNF was 0% and IBTR occurred in only one patient (1.82%) to the chest wall. Except for one patient (1.82%) had DM to lung and pleura and died from disease progression, the remaining patients were alive at the end of the 10-year follow-up. The 10-year DFS and OS were 94.55 and 98.18%. One patient (1.82%) was diagnosed with endometrial cancer after PBI. Except for 9 patients who declined the cosmetic assessment, the rest of the 46 patients (83.64%) were all rated as good and well-satisfied with the appearance of the irradiated breast. No breast retraction and fibrosis were observed in any of the patients. Additionally, only 4 patients experienced grade 1 late toxicity (7.28%). None had grade 3 or higher late toxicity.ConclusionThis is the first study to report the 10-year results of PBI after breast-conserving surgery in Chinese patients. Our study suggested that PBI had durable local control and maintained good cosmetic outcomes with minimal late toxicity at long term follow up for the early stage breast cancer patients.

Vertebral body fracture rates after stereotactic body radiation therapy compared with external-beam radiation therapy for metastatic spine tumors.

Stereotactic body radiation therapy (SBRT) is utilized to deliver highly conformal, dose-escalated radiation to a target while sparing surrounding normal structures. Spinal SBRT can allow for durable local control and palliation of disease while minimizing the risk of damage to the spinal cord; however, spinal SBRT has been associated with an increased risk of vertebral body fractures. This study sought to compare the fracture rates between SBRT and conventionally fractionated external-beam radiation therapy (EBRT) in patients with metastatic spine tumors. Records from patients treated at the University of California, San Francisco, with radiation therapy for metastatic spine tumors were retrospectively reviewed. Vertebral body fracture and local control rates were compared between SBRT and EBRT. Ninety-six and 213 patients were identified in the SBRT and EBRT groups, respectively. Multivariate analysis identified the need to control for primary tumor histology (p = 0.003 for prostate cancer, p = 0.0496 for renal cell carcinoma). The patient-matched EBRT comparison group was created by matching SBRT cases using propensity scores for potential confounders, including the Spinal Instability Neoplastic Score (SINS), the number and location of spine levels treated, sex, age at treatment, duration of follow-up (in months) after treatment, and primary tumor histology. Covariate balance following group matching was confirmed using the Student t-test for unequal variance. Statistical analysis, including propensity score matching and multivariate analysis, was performed using R software and related packages. A total of 90 patients met inclusion criteria, with 45 SBRT and 45 EBRT matched cases. Balance of the covariates, SINS, age, follow-up time, and primary tumor histology after the matching process was confirmed between groups (p = 0.062, p = 0.174, and 0.991, respectively, along with matched tumor histology). The SBRT group had a higher 5-year rate of vertebral body fracture at 22.22% (n = 10) compared with 6.67% (n = 3) in the EBRT group (p = 0.044). Survival analysis was used to adjust for uneven follow-up time and showed a significant difference in fracture rates between the two groups (p = 0.044). SBRT also was associated with a higher rate of local control (86.67% vs 77.78%). Patients with metastatic cancer undergoing SBRT had higher rates of vertebral body fractures compared with patients undergoing EBRT, and this difference held up after survival analysis. SBRT also had higher rates of initial local control than EBRT but this difference did not hold up after survival analysis, most likely because of a high percentage of radiosensitive tumors in the EBRT cohort.

36. A PROSPECTIVE TRIAL OF RESECTION PLUS SURGICALLY TARGETED RADIATION THERAPY FOR BRAIN METASTASIS

INTRODUCTIONAchieving durable local control for larger brain metastases remains problematic. Resection (R) alone is typically insufficient. Even with the addition of stereotactic radiation the 12-month recurrence rate for larger lesions (i.e., >2.5–3 cm) is 20% or more in many series. To improve outcomes we designed and prospectively evaluated a permanently implanted radiation device consisting of Cs-131 seeds positioned within a collagen tile (GammaTile, GT Medical Technologies, Tempe AZ). We combined maximum safe resection and collagen tile brachytherapy (CTBT) with the hypothesis that immediate radiation initiation and/or dose intensification could improve outcomes.MATERIALS/METHODSFrom 2013–2018 patients undergoing resection with either previously untreated or recurrent brain metastasis were enrolled on a single arm, multi-histology study (ClinicalTrials.gov, NCT#03088579). At resection completion the tumor bed was lined with collagen tiles imbedded with Cs-131, delivering 60–80 Gy at 5 mm depth. The device was designed to prevent direct source-to-brain contact and to maintain inter-source spacing after closure. No additional local therapy was given unless progression occurred.RESULTS16 metastases (12 recurrent/4 previously untreated) in 11 patients were treated. Median diameter 3.1 cm, range 1.9–5.1. Histology was 7 breast, 6 lung, and 3 sarcoma. Median age 60 years; 7 females/4 males. Average time for implantation was 5 minutes. At median radiographic follow-up of 9.5 months (range 0.1–25.2) treatment site progression occurred 1/16 (6%) at 10.9 months. Median treatment site time-to-progression (TTP) has not been reached (95% CI, >10.9 months). Median overall survival (OS) 9.3 months. No surgical adverse events occurred. One patient (6.2%) experienced radiation brain changes and was treated medically.CONCLUSIONR+CTBT demonstrated excellent safety and local control outcomes in this single-arm pre-commercial study. The device recently received FDA clearance for use in newly diagnosed and recurrent brain metastasis. Randomized clinical trials vs standard of care treatments are expected to open in 2020.

Dramatic radiotherapy response in a necrotic lymphoma mass: a case report

BackgroundDiffuse large B-cell lymphoma (DLBCL) represents the most common form of non-Hodgkin lymphoma and is characterized by an aggressive natural history. It often presents with rapid symptom development and disease progression. Most lymphomas are inherently radiosensitive, which allows for effective disease control from relatively low radiation doses. We report a case of a dramatic radiotherapy response in a necrotic diffuse large B-cell lymphoma mass in an elderly patient with early-stage diffuse large B-cell lymphoma, illustrating the potential for palliative radiotherapy to reduce disease burden in patients not fit for systemic therapy. There is no current consensus recommendation for radiotherapy treatment in this setting.Case presentationA 97-year-old Caucasian woman presented to the emergency department of our institution with a painful, malodorous, necrotic right upper neck mass, which had progressed over a two-month period. Investigations confirmed stage 1A diffuse large B-cell lymphoma. Palliative radiotherapy was delivered to a dose of 25 Gray (Gy) in five fractions on alternate days over two consecutive weeks. After four months, the mass completely resolved with no residual symptoms.ConclusionDramatic responses resulting in durable local control and improvement in quality of life are achievable with palliative radiotherapy, owing to the radiosensitivity of diffuse large B-cell lymphoma.

Postoperative, Single-Fraction Radiation Therapy in Merkel Cell Carcinoma of the Head and Neck

PurposeConventionally fractionated, postoperative radiation therapy (cPORT; 50 Gy in 25 fractions) is considered for patients with Merkel cell carcinoma (MCC) to improve locoregional control. However, cPORT is associated with acute toxicity, especially in the head and neck (H&N) region, and requires daily treatments over several weeks. We previously reported high rates of durable local control with minimal toxicity using 8-Gy single-fraction radiation therapy (SFRT) in the metastatic setting. We report early results on a cohort of patients with localized H&N MCC who received postoperative SFRT if a cPORT regimen was not feasible. Methods and MaterialsTwelve patients with localized MCC of the H&N (clinical/pathologic stages I-II) and no prior radiation therapy to the region were identified from an institutional review board-approved prospective registry who underwent surgical resection followed by postoperative SFRT. Time to event was calculated starting from the date of resection before SFRT. The cumulative incidence of in-field locoregional recurrences and out-of-field recurrences was estimated with death as a competing risk. ResultsTwelve patients with H&N MCC were identified with clinical/pathologic stages I-II H&N MCC. Median age at diagnosis was 81 years (range, 58-96 years); 25% had immunosuppression. At a median follow-up of 19 months (range, 8-34), there were no in-field locoregional recurrences. A single out-of-field regional recurrence was observed, which was successfully salvaged. There were no MCC-specific deaths. No radiation-associated toxicities greater than grade 1 (Common Terminology Criteria for Adverse Events v5) were observed. ConclusionsPreliminary data suggest that SFRT could offer a potential alternative to cPORT to treat the primary site for localized H&N MCC, particularly in elderly or frail patients, with promising in-field local control and minimal toxicity. Further data with validation in larger cohorts are needed to confirm the sustained safety and efficacy of postoperative SFRT.

The use of intraoperative radiation therapy in the management of locally recurrent rectal cancer

Locally recurrent rectal cancer (LRRC) is associated with substantial tumor- and treatment-related morbidity. Curative-intent surgical resection is challenging, and when used as a single modality, the results have been poor. Durable local control (LC) and long-term overall survival (OS) may be achieved with combined modality therapy including radiotherapy (RT), chemotherapy, and surgical resection. RT dose escalation utilizing intra-operative RT (IORT), when combined with external beam RT (EBRT), may offer improved LC particularly for those who have undergone sub-total resection. Curative treatment options are still feasible in patients who experience LR following previous pelvic RT, with data supporting the safety and efficacy of EBRT, surgery, and IORT as long as clinicians are cognizant of repeat RT exposure to small bowel. Advancement in patient selection, RT treatment techniques, and systemic therapies offer an interesting opportunity to improve outcomes for patients with LRRC and should be evaluated further in prospective studies.

The Evolving Role of Radiation Therapy in Patients with Metastatic Soft Tissue Sarcoma.

The management of metastatic disease is evolving. As systemic therapies continue to improve, there is increasing recognition that local therapy to distant sites of disease impacts outcomes among many histologies, including sarcoma. Various local therapy strategies exist, but radiation therapy (RT) is particularly critical as it provides a non-invasive, yet locally ablative strategy for metastatic management. Various delivery techniques including stereotactic body radiation therapy (SBRT) or hypofractionated RT can escalate the biologic dose while avoiding normal tissues in order to reduce tumor burden, provide durable local control, palliate symptoms, potentially prevent further seeding of metastatic lesions, and potentially prolong survival. This review summarizes the current state of the literature on the important role of RT for the treatment of metastatic sarcoma organized by the site of metastatic disease. Particularly for patients presenting with oligometastatic or oligoprogressive disease, consolidative RT is an important local therapy strategy to be considered in a multidisciplinary setting.

Immunotherapy and Radiation Therapy for Non-Small Cell Lung Cancer-A Stimulating Partnership.

Non-small cell lung cancer (NSCLC) is the most common subtype of lung cancer and the leading cause of cancer-related death. Although durable local control rates are high after surgical resection or definitive radiotherapy for early-stage disease, a substantial proportion of these patients eventually experience regional and/or distant failure and succumb to their metastatic disease. The discovery of immunotherapeutics and targeted biologics has revolutionized the treatment of locally advanced and metastatic disease, improving progression-free and overall survival when incorporated with the current standards of care. Notably, post-hoc analyses and early clinical trials provide a growing body of evidence to support a synergistic effect between radiation and immunotherapy for the treatment of NSCLC from early-stage to metastatic disease. Radiotherapy appears to be capable of not only potentiating the effect of immunotherapy in targeted lesions, but also eliciting an antitumor response in distant lesions without any direct exposure to radiation. This review explores the biologic basis of immunotherapy, targeted biologics, and radiotherapy as well as the preclinical and clinical data that support the combined use of radioimmunotherapy for early-stage, locally advanced, and metastatic NSCLC.

Stereotactic radiosurgery for the treatment of bulky spine metastases.

Stereotactic radiosurgery (SRS) has shown durable local control for the treatment of metastatic diseasespinal metastases. Multilevel disease or epidural or paraspinal involvement present challenges to achieving local control, and this study aims to analyze treatment outcomes for such lesions. Patients treated at a single institution with SRS to the spine from 2010-2018 were retrospectively reviewed. Inclusion criteria required clinical follow-up with either a pain assessment or imaging study. Bulky spine metastasis was defined as consisting of multilevel disease or epidural or paraspinal tumor involvement. 54 patients treated for 62 lesions met inclusion criteria. 42 treatments included at least two vertebrae, and 21and 31 had paraspinal and epidural involvement, respectively. Treatment regimens had a median 24Gy in 3 fractions to a volume of 37.75 cm3. Median follow-up was 14.36months, with 5 instances (8%) of local failure. Median overall survival was 13.32months. Pain improvement was achieved in 47 treatments (76%), and pain improved with treatment (p < 0.0001). Severe pain (HR = 3.08, p = 0.05), additional bone metastases (HR = 4.82, p = 0.05), and paraspinal involvement (HR = 3.93, p < 0.005) were predictive for worse overall survival. Kaplan-Meier analysis demonstrated that prior chemotherapy (p = 0.03) and additional bone metastases (p = 0.02) were predictive of worse overall survival. Grade < 3 toxicity was observed in 19 cases; no grade ≥ 3 side effects were observed. SRS can effectively treat bulky metastases to the spine, resulting in improvement of pain with minimal toxicity. Severe pain independently predicts for worse overall survival, indicating that treatment prior to worsening of pain is strongly recommended.

Stereotactic body radiation therapy in the treatment of ovarian cancer

BackgroundThis study evaluates the outcomes and toxicity of stereotactic body radiation therapy (SBRT) in ovarian cancer.MethodsThis retrospective analysis considered all patients treated with SBRT from 2009 to 2018 with a primary ovarian tumor. Follow-up included PET-CT and CT scans at 2–3 month intervals. Statistical analysis primarily consisted of univariate analysis, Cox proportional hazards analysis, and the Kaplan-Meier method.ResultsThe study included 35 patients with 98 treatments for lymph nodes (51), local recurrence (21), and de novo solid metastases (26). Median biologically effective dose (BED), gross tumor volume, and planning target volume were 38.40 Gy, 10.41 cc, and 25.21 cc, respectively. 52 lesions showed complete radiographic response, and two-year local control was 80%. Median overall survival (OS) was 35.2 months, and two-year progression-free survival (PFS) was 12%. On univariate analysis, Eastern Cooperative Oncology Group performance status > 0 was predictive of decreased OS (p = 0.0024) and PFS (p = 0.044). Factors predictive of local failure included lower BED (p = 0.016), treatment for recurrence (p = 0.029), and higher pre-treatment SUV (p = 0.026). Kaplan-Meier analysis showed BED ≤35 Gy (p < 0.005) and treatment for recurrence (p = 0.01) to be predictive of local failure. On Cox proportional hazards analysis, treatment of lymph nodes was predictive of complete radiographic response (hazard ratio (HR) = 4.95), as was higher BED (HR = 1.03). Toxicity included 27 cases of grade < 3 toxicity, and one grade 5 late toxicity of GI bleed from a radiation therapy-induced duodenal ulcer.ConclusionsSBRT provides durable local control with minimal toxicity in ovarian cancer, especially with BED > 35 Gy and treatment for lymph nodes.

Definitive re-irradiation of locally recurrent esophageal cancer after trimodality therapy in patients with a poor performance status.

There are few treatment guidelines for locally recurrent esophageal cancer after trimodality treatment (pre-operative chemoradiation followed by surgery) in patients with a poor performance status. The purpose of this single institutional, retrospective study was to evaluate the clinical outcomes and toxicities of definitive-intent re-irradiation for patients with recurrent esophageal cancer with a poor performance status [ECOG (Eastern Cooperative Oncology Group) ≥2]. Seven patients were identified with a median age of 74 years (range, 61-81 years). Four patients were ECOG 2 and three patients were ECOG 3. The median follow-up time after re-irradiation was 49 months. The median interval between initial radiotherapy and re-treatment was 32 months. Six patients received concurrent chemotherapy [carboplatin + paclitaxel in three patients; folinic acid, fluorouracil, oxaliplatin (FOLFOX) + 5-fluorouracil in one patient; FOLFOX in one patient, and capecitabine in one patient]. At the last follow-up, the six patients who underwent concurrent chemotherapy had stable disease (86%), while the one who did not receive chemotherapy progressed (14%). Two patients developed metastases. Three patients developed acute (<6 months) grade 4 toxicities (dysphagia, anemia, esophagitis). There were no early deaths attributable to treatment. Late toxicities (>6 months) were limited to grades 1 and 2 dysphagia and pneumonitis in four patients. In conclusion, definitive re-irradiation of recurrent esophageal cancer in patients with a poor performance status appears to be safe with acceptable acute toxicity and late complications. It also appears to result in durable local control when combined with chemotherapy, albeit with a small number of patients and limited follow-up.

Spine stereotactic radiosurgery for metastases from hepatobiliary malignancies: patient selection using PRISM scoring.

Dose escalation via stereotactic radiation therapy techniques has been necessary for hepatobiliary malignancies in the primary and oligometastatic setting, but such dose escalation is challenging for spine metastases due to spinal cord proximity. Here, we investigate the role of spine stereotactic radiosurgery (SSRS) in the management of such metastases. We retrospectively reviewed patients treated with SSRS to spinal metastases from hepatobiliary malignancies between 2004 and 2017 at our Institution. We used the Kaplan-Meier method to calculate overall survival (OS) and local control (LC) and Cox regression analysis to identify factors associated with disease-related outcomes. We identified 28 patients treated to 43 spinal metastases with SSRS for either HCC or cholangiocarcinoma. The 1-year LC and OS were 85% and 23%, respectively. The median time to death was 6.2months, while median time to local failure was not reached. Tumor volume > 60cc (SHR 6.65, p = 0.03) and Bilsky ≥ 1c (SHR 4.73, p = 0.05) predicted for poorer LC, while BED10 > 81Gy trended towards better local control (SHR 4.35, p = 0.08). Child-Pugh Class (HR 3.02, p = 0.003), higher PRISM Group (HR 3.49, p = 0.001), and systemic disease progression (HR 3.65, p = 0.001) were associated with worse mortality based on univariate modeling in patients treated with SSRS; on multivariate analysis, PRISM Group (HR 2.28, p = 0.03) and systemic disease progression (HR 2.67, p = 0.03) remained significant. Four patients (10%) developed compression deformity and one patient (2%) developed radiation neuritis. SSRS provides durable local control in patients with metastatic hepatobiliary malignancies, with higher BED necessary to ensure excellent LC. PRISM scoring is a promising prognostic tool to aid SSRS patient selection.

Efficacy and Toxicity of Stereotactic Body Radiotherapy for Early to Advanced Stage Hepatocellular Carcinoma – Initial Experience From an Australian Liver Cancer Service

AimsIntrahepatic progression remains the predominant mode of cancer-related death in hepatocellular carcinoma (HCC) underscoring the need for effective local therapies. We report our initial experience with liver stereotactic body radiotherapy (SBRT) in the management of early to advanced stage HCC at an Australian tertiary liver cancer service. Materials and methodsPatients with liver-confined HCC unsuitable for surgical resection or thermal ablation treated with SBRT between October 2013 and December 2018 were retrospectively evaluated. The primary end point was freedom from local progression. Secondary end points were progression-free survival, disease-specific survival, overall survival and toxicity. ResultsNinety-six patients were treated for 112 lesions (median size 3.8 cm, range 1.5–17 cm). The median follow-up was 13 months (range 3–65). Forty-six patients had received prior local therapies (median 1, range 1–5), 83 (86%) patients had cirrhosis with baseline Child–Pugh scores of A (88%) and B7–8 (12%). Fifty-nine (61%) patients had Barcelona Clinic Liver Cancer (BCLC) stage 0/A disease and 37 (39%) had stage B/C. Macrovascular invasion was present in 20 (21%). The median biologically effective dose (BED10) was 86 and 60 Gy for the BCLC 0/A and B/C cohorts, respectively. Freedom from local progression at 18 months was 94% for BCLC 0/A and 74% for BCLC B/C. Progression-free survival and overall survival at 12 months were 80 and 95% for BCLC 0/A and 40 and 71% for BCLC B/C, respectively. Five patients (7%) with cirrhosis and without disease progression had an increase in Child–Pugh score >1 within 3 months of SBRT, four of whom had intercurrent infections. Clinical toxicities grade ≥2 were reported in 20% of patients. ConclusionSBRT is an effective ablative modality for early stage HCC with low rates of significant toxicity. Lower dose SBRT can provide durable local control for advanced stage HCC. However, out-of-field relapse remains common, providing a rationale to investigate SBRT in combination with other therapies.

Outcomes and the Role of Primary Histology Following LINAC-based Stereotactic Radiation for Sarcoma Brain Metastases.

The brain is a rare site for sarcoma metastases. Sarcoma's radioresistance also makes standard whole-brain radiotherapy less appealing. We hypothesize that stereotactic radiation techniques (stereotactic radiosurgery [SRS]/stereotactic fractionated radiotherapy [FSRT]) may provide effective local control. This single-institution retrospective analysis evaluated our experience with linear acceleator-based SRS/FSRT for sarcoma brain metastases. Time to event analysis was estimated via Kaplan-Meier. Univariable/multivariable Cox regression analyses followed to assess the impact of patient and disease characteristics on outcomes. Between 2003 and 2018, 24 patients were treated with 34 courses of SRS/FSRT to 58 discrete lesions. The median age at first treatment was 57 years (range: 25 to 87 y). Majority of patients had concurrent lung metastases (n=21; 88%), diagnosed spindle cell sarcoma (n=15; 25%) or leiomyosarcoma (n=12; 21%) histology, and were treated with either SRS (n=43; median dose=19 Gy, range: 15 to 24 Gy) or FSRT (n=17; 3/5 fractions, median dose=25 Gy, range: 25 to 35 Gy). With a median follow-up after brain metastasis of 7.3 months, the 6 month/12 month local control, distant brain control, and overall survival of 89%/89%, 59%/34%, and 50%/38%, respectively. All local failures were of primary spindle cell histology (P<0.001), which was associated with poorer distant control (hazard ratio=25.8, 95% confidence interval: 3.1-536.4; P=0.003) on univariable analysis, and OS (hazard ratio=7.1, 95% confidence interval: 2.0-26.1; P=0.003) on multivariable analysis. This is the largest patient cohort with sarcoma brain metastases treated with SRS/FSRT, it provides durable local control, despite a reputation for radioresistance. Further prospective evidence is required to determine the impact of primary histology on control and survival following brain metastasis diagnosis.

Response to hyperfractionated accelerated radiotherapy in chemotherapy-refractory non-Hodgkin lymphoma

Patients with chemotherapy-refractory non-Hodgkin lymphoma (NHL) have a poor prognosis with a median overall survival (OS) of only 10 months. To investigate the role of radiotherapy (RT) in such patients, we conducted a retrospective review of 17 patients with biopsy-proven refractory NHL who received hyperfractionated accelerated RT between 2000 and 2017. Forty-seven percent had stages I and II and 53% had stages III and IV disease. Majority (59%) had diffuse large B-cell lymphoma. One-year local control rate was 82%. Fifty-nine percent proceeded to hematopoietic stem cell transplantation (HSCT). At a median follow-up time of 8.8 months (range: 13 days to 17.4 years), 10 were alive with five in remission. Six patients were long-term survivors with a median OS of 8.1 years. Hyperfractionated accelerated RT in chemotherapy-refractory NHL provides durable local disease control in the majority of cases. Combined with HSCT, the RT regimen may also provide long-term disease remission in a subset of patients.

Spine stereotactic radiosurgery for metastatic thyroid cancer: a single-institution experience.

Patients with metastatic thyroid cancer have prolonged survival compared to those with other primary tumors. The spine is the most common site of osseous involvement in cases of metastatic thyroid cancer. As a result, obtaining durable local control (LC) in the spine is crucial. This study aimed to evaluate the efficacy of spine stereotactic radiosurgery (SSRS) in patients with metastatic thyroid cancer. Information on patients with metastatic thyroid cancer treated with SSRS for spinal metastases was retrospectively evaluated. SSRS was delivered with a simultaneous integrated boost technique using single- or multiple-fraction treatments. LC, defined as stable or reduced disease volume, was evaluated by examining posttreatment MRI, CT, and PET studies. A total of 133 lesions were treated in 67 patients. The median follow-up duration was 31 months. Dose regimens for SSRS included 18 Gy in 1 fraction, 27 Gy in 3 fractions, and 30 Gy in 5 fractions. The histology distribution was 36% follicular, 33% papillary, 15% medullary, 13% Hurthle cell, and 3% anaplastic. The 1-, 2-, and 5-year LC rates were 96%, 89%, and 82%, respectively. The median overall survival (OS) was 43 months, with 1-, 2-, and 5-year survival rates of 86%, 74%, and 44%, respectively. There was no correlation between the absolute biological equivalent dose (BED) and OS or LC. Patients with effective LC had a trend toward improved OS when compared to patients who had local failure: 68 versus 28 months (p = 0.07). In terms of toxicity, 5 vertebral compression fractures (2.8%) occurred, and only 1 case (0.6%) of greater than or equal to grade 3 toxicity (esophageal stenosis) was reported. SSRS is a safe and effective treatment option with excellent LC and minimal toxicity for patients with metastatic thyroid cancer. No association with increased radiation dose or BED was found, suggesting that such patients can be effectively treated with reduced dose regimens.