IMRT Reduces Acute Toxicity in Patients Treated With Preoperative Chemoradiation for Gastric Cancer.

PURPOSE: Preoperative chemoradiation is being currently evaluated in 2 randomized international trials. However, chemoradiation for gastric cancer can be associated with relatively high rates of acute toxicity. We compared rates of toxicity, toxicity-related events, and oncologic outcomes in patients treated with intensity modulated radiation therapy (IMRT) and those treated with 3-dimensional conformal radiation therapy (3DCRT). METHODS AND MATERIALS: We retrospectively reviewed records of 202 patients with consecutive gastric cancer treated with preoperative intent radiation therapy at our institution from 1998 to 2018. Patients with gastroesophageal junction involvement and those with metastatic disease were excluded. Eighty-two patients received 3DCRT, and 120 patients received IMRT. The median radiation dose was 45 Gy, and 99% received concurrent chemotherapy. RESULTS: There were no significant differences between the 3DCRT and IMRT groups regarding sex, race, histology, tumor location, histology, or nodal stage. The rate of grade 3 to 4 acute toxicity was significantly lower in patients treated with IMRT compared with 3DCRT (49% vs 70%, P = .004). The composite rate of toxicity-related events (hospitalization, feeding tube use, intravenous rehydration, or radiation therapy breaks) was also significantly lower in patients treated with IMRT compared with 3DCRT (56% vs 85%, P <.001). In addition, 68% of patients who received IMRT and 73% of patients who received 3DCRT underwent subsequent surgical resection (P = .245). Among patients who underwent surgery, the 3-year overall survival rates were not significantly different between those treated with IMRT and 3DCRT (71% vs 69%, P = .786). Patients receiving IMRT had a significantly higher absolute nadir lymphocyte count compared with patients receiving 3DCRT (median, 0.21 vs 0.16 K/UL; P = .047). CONCLUSIONS: Our study suggests that IMRT might significantly reduce rates of grade 3 to 4 acute toxicity and toxicity-related events compared with 3DCRT, with no significant difference in oncologic outcomes. IMRT is an appropriate and possibly preferable radiation modality in patients treated with preoperative chemoradiation for gastric cancer.

Low incidence of late failure and toxicity after spine stereotactic radiosurgery: Secondary analysis of phase I/II trials with long-term follow-up.

BACKGROUND AND PURPOSE: To characterize local control and late toxicity in long-term survivors prospectively-treated with spine stereotactic radiosurgery (SSRS). MATERIALS AND METHODS: From 2002 to 2011, 228 patients were prospectively-treated on protocol for metastatic disease of 261 vertebral sites. A subset of 52 patients surviving >4 years following treatment were collectively treated for 58 sites (encompassing 69 vertebrae) and underwent secondary analysis. Of all sites, 9% received prior radiation, and 16% encompassed multiple contiguous vertebrae. Radiation prescriptions were most commonly 24 Gy in 1 and 27 Gy in 3 fractions. Outcomes were evaluated via Kaplan-Meier, and associations analyzed via logistic regression. RESULTS: Median follow-up was 6.7 years (range: 49-142 months). Five-year local control by site was 91%, with late failures (>2 years) occurring in 3%. Overall and Grade ≥3 late toxicities (>2 years) were observed in 5% and 2% of sites. The last known neurologic event (grade 2 radiculopathy) was noted 2.1 years post-treatment, while the last documented fracture occurred at 4.1 years. No Grade ≥3 events were witnessed after 3.1 years post-SSRS, and no toxicities were noted after 4.1 years through end of follow-up. Re-irradiation, number of segments treated per site (1 vs. 2-3), and fractionation (1 vs. 3-5) were not associated with failure or toxicity. CONCLUSION: SSRS maintains excellent disease control and a favorable late toxicity profile even among long-term survivors, with very few failures or toxicities after 2 years in this prospectively-treated population. Overall, these data support the durable control and long-term safety of SSRS with extended follow-up.

Volumetric assessment of apparent diffusion coefficient predicts outcome following chemoradiation for cervical cancer.

OBJECTIVE: To determine the utility of volumetric diffusion weighted imaging (DWI) compared to other clinical factors for predicting recurrence and survival in cervical cancer patients treated with definitive chemoradiation. METHODS AND MATERIALS: We retrospectively studied cervical cancer patients treated with definitive chemoradiation between 2009-2013 at a single institution with a baseline MRI with DWI and 18F-FDG positron emission tomography/computed tomography (FDG-PET) scan. To identify clinical and imaging metrics correlated with survival and recurrence endpoints, variable importance values were calculated from random forest models. To provide clinically relevant threshold values, recursive partitioning analysis dichotomized patients into potential risk groups based on selected metrics. Cox's proportional hazard models assessed the effect of clinical and imaging factors on survival endpoints. RESULTS: Ninety-three patients were included in the analysis (median age 50 years). At a median follow-up of 35.6 months, 32 patients (34%) had disease recurrence. In the best multivariate model including clinical and imaging parameters, 90th percentile ADC < 1.917 was the only significantly associated factor with worse progression free survival (PFS). Overall survival, PFS, and distant metastasis free survival (DMFS) were significantly different between patient groups divided on 90th percentile ADC with threshold of 1.917 × 10-3 mm2/s and MRI volume with threshold of 18.9 cc (P = 0.037, P = 0.0002, P = 0.001). High MRI volume and low ADC were associated with worse clinical outcomes. CONCLUSIONS: Volumetric 90th percentile ADC value of the primary tumor on pretreatment MRI was a significant predictor of PFS and DMFS in cervical cancer patients, independent of established clinical factors and SUV on FDG-PET.

Use of three pins in Gamma Knife stereotactic radiosurgery for brain metastases.

PURPOSE: We present our institutional experience in treating brain metastases with GK-SRS and a headframe fixed to the skull with only 3 pins to avoid collisions between the headframe and the Gamma Knife (GK) machine. METHODS AND MATERIALS: Among 3500 consecutive patients who received GK-SRS in 2011-2017, 50 had 1 of the 2 anterior pins removed immediately before treatment of ≥1 brain lesion. Endpoints were local control, dosimetric parameters, and toxicity. RESULTS: Median follow-up time for the 49 patients with follow-up was 7.0 months (range 0.2-57.0). Median number of lesions treated per session was 6 (range 1-18); a median 1 lesion was treated with 3-pin fixation (range 1-2) and a median 5 lesions treated with 4-pin fixation (range 0-17) during the same session. Lesions treated with 3-pin fixation were in the occipital lobe (n=41), cerebellum (n=9), or temporal lobe (n=1). No local failures were noted. The sole grade 2 toxicity (partial seizure) was attributed to treatment of a 4-pin-fixed lesion. Except for gradient index, dosimetry did not vary for lesions treated with 3-pin versus 4-pin fixation. CONCLUSIONS: Treating brain metastases with 3-pin fixation did not compromise treatment outcome and is a good option for posterior brain metastases that cannot otherwise be treated with 4-pin GK-SRS.

Reirradiation of head and neck cancer using modern highly conformal techniques.

Locoregional disease recurrence or development of a second primary cancer after definitive radiotherapy for head and neck cancers remains a treatment challenge. Reirradiation utilizing traditional techniques has been limited by concern for serious toxicity. With the advent of newer, more precise radiotherapy techniques, such as intensity-modulated radiotherapy (IMRT), proton radiotherapy, and stereotactic body radiotherapy (SBRT), there has been renewed interest in curative-intent head and neck reirradiation. However, as most studies were retrospective, single-institutional experiences, the optimal modality is not clear. We provide a comprehensive review of the outcomes of relevant studies using these 3 head and neck reirradiation techniques, followed by an analysis and comparison of the toxicity, tumor control, concurrent systemic therapy, and prognostic factors. Overall, there is evidence that IMRT, proton therapy, and SBRT reirradiation are feasible treatment options that offer a chance for durable local control and survival. Prospective studies, particularly randomized trials, are needed.

Stereotactic radiosurgery for trigeminal pain secondary to recurrent malignant skull base tumors.

OBJECTIVE: The objective of this study was to assess outcomes after Gamma Knife radiosurgery (GKRS) re-irradiation for palliation of patients with trigeminal pain secondary to recurrent malignant skull base tumors. METHODS: From 2009 to 2016, 26 patients who had previously undergone radiation treatment to the head and neck received GKRS for palliation of trigeminal neuropathic pain secondary to recurrence of malignant skull base tumors. Twenty-two patients received single-fraction GKRS to a median dose of 17 Gy (range 15-20 Gy) prescribed to the 50% isodose line (range 43%-55%). Four patients received fractionated Gamma Knife Extend therapy to a median dose of 24 Gy in 3 fractions (range 21-27 Gy) prescribed to the 50% isodose line (range 45%-50%). Those with at least a 3-month follow-up were assessed for symptom palliation. Self-reported pain was evaluated by the numeric rating scale (NRS) and MD Anderson Symptom Inventory-Head and Neck (MDASI-HN) pain score. Frequency of as-needed (PRN) analgesic use and opioid requirement were also assessed. Baseline opioid dose was reported as a fentanyl-equivalent dose (FED) and PRN for breakthrough pain use as oral morphine-equivalent dose (OMED). The chi-square and Student t-tests were used to determine differences before and after GKRS. RESULTS: Seven patients (29%) were excluded due to local disease progression. Two experienced progression at the first follow-up, and 5 had local recurrence from disease outside the GKRS volume. Nineteen patients were assessed for symptom palliation with a median follow-up duration of 10.4 months (range 3.0-34.4 months). At 3 months after GKRS, the NRS scores (n = 19) decreased from 4.65 ± 3.45 to 1.47 ± 2.11 (p < 0.001); MDASI-HN pain scores (n = 13) decreased from 5.02 ± 1.68 to 2.02 ± 1.54 (p < 0.01); scheduled FED (n = 19) decreased from 62.4 ± 102.1 to 27.9 ± 45.5 mcg/hr (p < 0.01); PRN OMED (n = 19) decreased from 43.9 ± 77.5 to 10.9 ± 20.8 mg/day (p = 0.02); and frequency of any PRN analgesic use (n = 19) decreased from 0.49 ± 0.55 to 1.33 ± 0.90 per day (p = 0.08). At 6 months after GKRS, 9 (56%) of 16 patients reported being pain free (NRS score 0), with 6 (67%) of the 9 being both pain free and not requiring analgesic medications. One patient treated early in our experience developed a temporary increase in trigeminal pain 3-4 days after GKRS requiring hospitalization. All subsequently treated patients were given a single dose of intravenous steroids immediately after GKRS followed by a 2-3-week oral steroid taper. No further cases of increased or new pain after treatment were observed after this intervention. CONCLUSIONS: GKRS for palliation of trigeminal pain secondary to recurrent malignant skull base tumors demonstrated a significant decrease in patient-reported pain and opioid requirement. Additional patients and a longer follow-up duration are needed to assess durability of symptom relief and local control.

Reirradiation of thoracic cancers with intensity modulated proton therapy.

PURPOSE: Reirradiation of thoracic malignancies is a treatment challenge, with concerns for toxicity and the inability to deliver definitive doses. Intensity modulated proton therapy (IMPT) may allow safe delivery of a higher dose of radiation to the tumor while minimizing toxicities. METHODS AND MATERIALS: Between 2011 and 2016, 27 patients who received IMPT for reirradiation of thoracic malignancies with definitive intent were retrospectively analyzed. Patients were included if they received a prior thoracic radiation course. All doses were recalculated to an equivalent dose in 2-Gy fractions (EQD2). Patients received IMPT to a median dose of 66 EQD2 Gy (range, 43.2-84 Gy) for recurrence of thoracic cancer (93%) or sequentially after a course of thoracic stereotactic ablative radiation therapy (7%). RESULTS: Twenty-two patients (81%) were treated for non-small cell lung cancer. The median time to reirradiation was 29.5 months. At a median follow-up for all patients of 11.2 months (25.9 surviving patients), the median overall survival was 18.0 months, with a 1-year overall survival of 54%. Four patients (15%) experienced an in-field local failure (LF), with a 1-year freedom from LF rate of 78%. The 1-year freedom from locoregional failure and 1-year progression-free survival rates were 61% and 51%, respectively. Patients who received 66 EQD2 Gy or higher had improved 1-year freedom from LF (100% vs 49%; P = .013), 1-year freedom from locoregional failure (84% vs 23%; P = .035), and 1-year progression-free survival (76% vs 14%; P = .050). Reirradiation was well tolerated, with only 2 patients (7%) experiencing late grade 3 pulmonary toxicity, and none with grade 3 or higher esophagitis. There were no grade 4-5 toxicities. CONCLUSIONS: These data represent the largest series of patients treated with IMPT for definitive reirradiation of thoracic cancers. They demonstrate that IMPT provided durable local control with minimal toxicity and suggest that higher doses may improve outcomes.

Reirradiation of Skull Base Tumors With Advanced Highly Conformal Techniques.

PURPOSE OF REVIEW: Skull base reirradiation is challenging due to complex anatomy, enrichment of treatment-resistant clonogens, and increased risk of severe treatment complications. Without local therapy, early mortality is certain and tumor progression can result in debilitating symptoms. Modern radiotherapy advancements, such as image-guided radiation therapy (IGRT), intensity-modulated radiation therapy (IMRT), particle therapy, and stereotactic radiation therapy (SRT), are attractive for skull base reirradiation. RECENT FINDINGS: Although limited by their retrospective nature and heterogeneous patient populations, several studies have demonstrated that reirradiation with these highly conformal techniques is feasible. Compared to IMRT or particle therapy reirradiation, SRT reirradiation appears promising with lower toxicity and increased convenience. Here, we provide thorough explanations for each technology and summarize the most relevant and recent studies, with particular attention to efficacy and toxicity. Skull base reirradiation using these extremely conformal therapy techniques requires meticulous treatment planning and should be delivered by experienced teams.

Radiation therapy improves survival in patients with testicular diffuse large B-cell lymphoma.

In 120 Stage I-IV testicular diffuse large B-cell lymphoma (DLBCL) patients treated from 1964 to 2015, we assessed the benefits of prophylactic contralateral testicular radiation (RT) and prophylactic central nervous system (CNS) therapy on overall, progression free, testicular relapse free, and CNS relapse free survival (OS, PFS, TRFS, and CRFS, respectively). Seventy percent of patients received RT, 53% received anthracyclines and rituximab (modern therapy), and 61% received CNS prophylaxis. On univariate analysis RT was associated with improved TRFS, PFS, and trended toward improved OS. On multivariate analysis (MVA), RT was significantly associated with improved OS and PFS; the PFS benefit persisted among patients receiving modern therapy. CNS prophylaxis was associated with improved OS, PFS, and TRFS, but not CRFS on univariate analysis, and was not significant on MVA. RT is associated with improved survival, and should be considered for all testicular DLBCL patients, but additional strategies are needed to prevent CNS relapse.

Diffusion-Weighted Magnetic Resonance Imaging as a Predictor of Outcome in Cervical Cancer After Chemoradiation.

PURPOSE: To determine whether apparent diffusion coefficient (ADC) value is predictive of survival after definitive chemoradiation for cervical cancer independent of established imaging and clinical prognostic factors. METHODS AND MATERIALS: Between 2011 and 2013, the pretreatment MRI scans for 69 patients treated with definitive chemoradiation for newly diagnosed cervical cancer were retrieved. Scans were acquired with a 1.5-T magnetic resonance scanner, including diffusion-weighted imaging sequences. Mean ADC value was measured within a region of interest in the primary cervical cancer on the baseline MRI scan. Baseline tumor maximum standardized uptake value on positron emission tomography/computed tomography was determined by the reading radiologist. Treatment included external beam radiation therapy to the pelvis followed by brachytherapy in 97%, and with concurrent weekly cisplatin in 99% of patients. Univariate and multivariate analyses were done to investigate the association of clinical and imaging variables with disease control and survival endpoints using a Cox proportional hazard test. RESULTS: Median follow-up was 16.7 months (range, 3.1-44.2 months). The 1-year overall survival, locoregional recurrence-free survival, and disease-free survival rates were 91%, 86%, and 74%, respectively. The median ADC value was 0.941 × 10-3 mm2/s (range, 0.256-1.508 × 10-3 mm2/s). The median standardized uptake value in the primary tumor was 15 (range, 6.2-43.4). In multivariate analysis, higher ADC value (hazard ratio [HR] 0.36, 95% confidence interval [CI] 0.15-0.85, P=.02), higher stage (HR 2.4, 95% CI 1.1-5.5, P=.033), and nonsquamous histology (HR 0.23, 95% CI 0.07-0.82, P=.024) were independent predictors of disease-free survival. CONCLUSIONS: The mean ADC value of the primary tumor on pretreatment MRI was the only imaging feature that was an independent predictor of disease-free survival in cervical cancer patients treated with chemoradiation. Further validation will be needed to determine whether ADC values may prove useful in identifying cervical patients at high risk of recurrence.

The use of spine stereotactic radiosurgery for oligometastatic disease.

OBJECTIVE The authors investigated the outcomes following spine stereotactic radiosurgery (SSRS) for patients with oligometastatic disease of the spine. METHODS The study was a secondary analysis of 38 of 209 patients enrolled in 2 separate institutional Phase I/II prospective protocols and treated with SSRS between 2002 and 2011. Of these 38 patients, 33 (87%) were treated for a solitary spine metastasis, with no other history of metastatic disease. SSRS was prescribed to 24 Gy in 1 fraction (8%), 18 Gy in 1 fraction (18%), 16 Gy in 1 fraction (11%), 27 Gy in 3 fractions (53%), 30 Gy in 5 fractions (8%), or 20 Gy in 5 fractions (3%). Seventeen patients (45%) received prior conventional external beam radiation therapy. RESULTS The median overall survival (OS) was 75.7 months, and the 2- and 5-year OS rates were 84% and 60%, respectively. In multivariate analysis, patients who had prior spine surgery and a better Karnofsky Performance Scale score had an improved OS (HR 0.16, 95% CI 0.05-0.52, p < 0.01, and HR 0.33, 95% CI 0.13%-0.84%, p = 0.02, respectively), and those who had undergone prior radiation therapy had a worse OS (HR 3.6, 95% CI 1.2%-10%, p = 0.02). The 1-, 2-, and 5-year local progression-free survival rates were 85%, 82%, and 78%, respectively. The median time to systemic therapy modification was 41 months. Two patients (5%) experienced late Grade 3-4 toxicity. CONCLUSIONS Patients with oligometastatic disease of the spine treated with SSRS can experience long-term survival and a long time before needing a modification in systemic therapy. In addition, SSRS leads to excellent local control and minimal late toxicity.

Gamma Knife Stereotactic Radiosurgery for Brain Metastases Using Only 3 Pins.

BACKGROUND: Removal of a pin during Gamma Knife stereotactic radiosurgery (GK-SRS) may be necessary to prevent collision and allow treatment. OBJECTIVE: To investigate outcomes after GK-SRS for treatment of brain metastases using a head frame immobilized to the skull with only 3 pins. METHODS: Between 2009 and 2014, we retrospectively reviewed the records of 1971 patients and identified 20 patients with multiple brain metastases treated with GK-SRS in which 1 anterior pin was removed immediately before treatment of a single posterior lesion. GK-SRS was also delivered to 116 other lesions in these 20 patients using the standard 4 pins during the same session, serving as an internal control for comparison. Endpoints included local control, dosimetric parameters, toxicity, and overall survival. RESULTS: The median number of lesions treated per session was 6 (range, 2-14). The lesions treated using 3 pins were located in the occipital lobe (n = 14) or the cerebellum (n = 6). Median follow-up was 12.3 months. There was 1 local failure involving a control lesion. Lesions treated using 3 pins had a lower prescription isodose line. GK-SRS of a lesion using 3 pins did not cause any clinical toxicities or increase in radiographic edema or hemorrhage. CONCLUSION: Treating posteriorly located brain metastases with GK-SRS using only 3 pins provided excellent local control and no difference in treatment toxicity, which may make it a safe and reasonable option for lesions that may otherwise be difficult to treat.

Management of nodal recurrences of endometrial cancer with IMRT.

OBJECTIVE: Pelvic and paraortic lymph nodal regions are frequent sites of relapse in women with endometrial cancer who have not undergone adjuvant external beam radiation. We investigated outcomes after definitive management of nodal relapses of endometrial cancer with intensity modulated radiation therapy (IMRT). METHODS: Between 2002-2012, 38 patients with endometrial cancer who had no prior external beam radiation were treated definitively using IMRT for regionally confined pelvic or paraortic nodal recurrences. Thirteen (34%) had chemotherapy prior to radiation, and 21 (55%) received concurrent chemotherapy. The nodal basins were typically treated to 45-50Gy, with a boost to the gross tumor to a median total of 64.7Gy (range 59-73Gy). RESULTS: The median overall survival from date of recurrence was 46.1months and the 2-year survival was 71%. Patients who received concurrent chemotherapy had a significantly longer median survival (61.9months versus 28.7months, p=0.034). In-field failures were more frequent in patients who received chemotherapy prior to radiation, had a shorter recurrence-free interval, received a lower radiation dose, and had higher tumor grade. Three patients (8%) experienced grade 3-4 late gastrointestinal (GI) toxicity. CONCLUSIONS: Long-term survival can be achieved in women with nodal recurrences of endometrial cancer. The use of concurrent chemotherapy and dose escalation with IMRT as feasible may improve survival for women with isolated nodal recurrences of endometrial cancer.