Impact of bowel space contouring variability on radiation dose and volume assessments in treatment planning for gynaecologic cancers.

INTRODUCTION: Correlations between radiation dose/volume measures and small bowel (SB) toxicity are inconsistent in the medical literature. We assessed the impact of inter-provider variation in bowel bag contouring technique on estimates of radiation dose received by the SB during pelvic radiotherapy. METHODS: Ten radiation oncologists contoured rectum, bladder and bowel bags on treatment planning computed tomography (CT) scans of two patients receiving adjuvant radiation for endometrial cancer. A radiation plan was generated for each patient and used to determine the radiation dose/volume for each organ. Kappa statistics were applied to assess the inter-provider contouring agreement, and Levene test evaluated the homogeneity of variance for radiation dose/volume metrics, including the V45Gy (cm3 ). RESULTS: The bowel bag showed greater variation in radiation dose/volume estimates compared to the bladder and rectum. The V45Gy ranged from 163 to 384 cm3 for data set A and 109 to 409 cm3 for dataset B. Kappa values were 0.82/0.83, 0.92/0.92 and 0.94/0.86 for the bowel bag, rectum, and bladder on data sets A/B, demonstrating lower inter-provider agreement for bowel bag compared with bladder and rectum. CONCLUSION: Inter-provider contouring variability is more significant for the bowel bag than the rectum and bladder, with an associated greater variability in dose and volume estimates during radiation planning.

Treatment Tolerance of Cetuximab versus Alternative Chemotherapy Agents in Non-Cisplatin Candidates with Head and Neck Cancer Receiving Concurrent Chemoradiotherapy.

INTRODUCTION: Standard of care for radiosensitization in head and neck squamous cell carcinoma (HNSCC) is concurrent chemoradiotherapy (CCRT) with high-dose cisplatin. The optimal chemoradiation regimen for patients medically unfit for cisplatin is unclear. We compared our experience with concurrent cetuximab (CTX) versus other cytotoxic non-cisplatin agents. METHODS: We reviewed 53 patients between 2011 and 2017 with HNSCC treated with CCRT ineligible for cisplatin. Chemotherapy and radiotherapy treatment tolerance was evaluated in those receiving CTX versus non-CTX chemotherapy (NCC). Of the NCC regimens, the majority were carboplatin/paclitaxel and were dosed at an area under the curve (AUC) of 2 and 45-50 mg/m2, respectively. Standard radiation dosing was 70 Gray (Gy) in the definitive setting and 60-66 Gy in the postoperative setting. Patient characteristics and treatment toxicities were evaluated using categorical methods. RESULTS: Patients were well balanced overall including differences between performance status and the comorbidity score. NCC patients experienced more radiation treatment breaks (52.4% vs. 21.9%, p = 0.022), radiation delays >1 week (33.3% vs. 3.1%, p < 0.01), and chemotherapy dose-limiting toxicity (61.9% vs. 28.1%, p = 0.015) compared to CTX patients. Nutritional dependence on a PEG tube was more likely in the NCC cohort (52.4% vs. 22.6%, p = 0.027). CONCLUSION: Our results suggest decreased treatment tolerance in non-cisplatin cytotoxic chemotherapy compared to cetuximab. Further prospective study is needed to clarify optimal chemotherapy in patients unable to receive cisplatin.

Sarcopenia and Treatment Toxicity in Older Adults Undergoing Chemoradiation for Head and Neck Cancer: Identifying Factors to Predict Frailty.

This study was performed to identify treatment related toxicities in older adults undergoing concurrent chemoradiotherapy for head and neck cancer and nutritional and skeletal muscle measures that might identify frailty. Imaging analysis was done with the following skeletal muscle measurements: skeletal muscle index (SMI), skeletal muscle density (SMD), and skeletal muscle gauge (SMG). Patients were dichotomized by age into younger (<70 years old, 221 patients) and older age groups (≥70 years old, 51 patients). Low SMI was more common in older patients (86.7%) compared to younger patients (51.7%, p < 0.01), as were low SMD (57.8% vs. 37.3%, p = 0.012) and low SMG (76.1% vs. 44.2%, p < 0.01), despite having similar BMIs (27.3 kg/m2 versus 27.7 kg/m2, p = 0.71). Older patients were significantly more likely to experience chemotherapy toxicity than younger patients (54.9% versus 32.3%, p < 0.01). On multivariate analysis age (p < 0.01), current smoking status (p < 0.01), and low SMI (p < 0.01) remained as significant predictors for missed chemotherapy cycles or discontinuation. Older patients were more likely to require ≥5-day radiation breaks than younger patients (27.5% versus 8.6%, p < 0.01). On multivariate analysis, age (p < 0.01), low albumin status (p = 0.03), and low SMI (p = 0.04) were identified as predictors of prolonged radiation treatment breaks. Based on the results of our study, sarcopenia may be used as an additional marker for frailty alongside traditional performance status scales.

Stereotactic Body Radiation Therapy for Apical Lung Tumors: Dosimetric Analysis of the Brachial Plexus and Preliminary Clinical Outcomes.

PURPOSE: Dosimetric constraints of the brachial plexus have not yet been well-established for patients undergoing stereotactic body radiation therapy (SBRT). This study evaluated long-term experience with the treatment of early-stage apical lung tumors with SBRT and reports on dosimetric correlates of outcome. METHODS AND MATERIALS: Between 2009 and 2018, a total of 78 consecutive patients with 81 apical lung tumors underwent SBRT for T1-3N0 non-small cell lung cancer. Apical tumors were those with tumor epicenter superior to the aortic arch. The brachial plexus (BP) was anatomically contoured according to the Radiation Therapy Oncology Group atlas. Patient medical records were reviewed retrospectively to determine incidence of brachial plexus injury (BPI) and a normal tissue complication probability model was applied to the dosimetric data. RESULTS: Five patients (6.4%) reported neuropathic symptoms consistent with BPI and occurred a median 11.9 months after treatment (range, 5.2-28.1 months). Most common dose and fractionation in those developing BPI were 50 Gy in 5 fractions (4 patients). Symptoms consisted of pain in 2 patients (40.0%), numbness in the hand or axilla in 4 patients (80.0%), and ipsilateral hand weakness in 1 patient (20.0%). In the overall cohort the median BP Dmax (EQD23 Gy) was 5.13 Gy (range, 0.18-217.2 Gy) and in patients with BPI the median BP Dmax (EQD23 Gy) was 32.14 Gy (range, 13.4-99.9 Gy). The normal tissue complication probability model gave good fit with an area under the curve of 0.75 (odds ratio, 7.3; 95% confidence interval, 0.8-68.3) for BP Dmax (EQD23 Gy) threshold of 20 Gy. CONCLUSIONS: Significant variation exists in the dose delivered to the brachial plexus for patients treated by SBRT for apical lung tumors. The incidence of neuropathic symptoms in the post-SBRT setting was appreciable and prospective clinical correlation with dosimetric information should be used to develop evidence-based dose constraints.

The impact of sarcopenia on tolerance of radiation and outcome in patients with head and neck cancer receiving chemoradiation.

BACKGROUND AND PURPOSE: Sarcopenia is a predictor of poor prognosis in cancer patients. One potential mechanism for worse outcomes in sarcopenic patients is worse tolerance to treatment; this has not been investigated with regard to radiation treatment. We reviewed our institutional experience of head and neck cancer patients receiving concurrent chemoradiation and assessed outcomes with respect to sarcopenia. MATERIALS AND METHODS: Patients treated between 2012 and 2016 were reviewed. Sarcopenia was assessed from radiation planning computed tomography (CT) scans using muscles at the C3 vertebral body using previously published methods. Survival was calculated using the Kaplan-Meier method. Association between patient factors and outcome was calculated in univariate and multivariate analyses. RESULTS: Two hundred and forty-six patients were included. Fifty-eight percent met criteria for sarcopenia. Thirty-seven percent experienced chemotherapy delays of >1 week and 14% had radiation treatment breaks >1 week. On multivariate analysis, concurrent smoking (HR 3.85, p < 0.01) and sarcopenia (HR 2.15, p = 0.01) were associated with chemotherapy toxicity and age >65 years (HR 2.94, p < 0.01) and sarcopenia (HR 2.99, p = 0.04) were associated with prolonged radiation breaks. Sarcopenia was associated with worse overall survival (HR 1.83, p = 0.03) and progression-free survival (HR 1.65, p = 0.03) in the overall cohort. When analyzed separately, sarcopenia was not associated with outcomes in p16-positive oropharynx cancers. CONCLUSION: Sarcopenic patients receiving concurrent chemoradiation are more likely to require radiation treatment breaks and suffer chemotherapy toxicity than their non-sarcopenic counterparts. This may contribute to worse survival outcomes in head and neck cancer, with the exception of p16-positive oropharyngeal cancer.

Weekly cisplatin chemotherapy dosing versus triweekly chemotherapy with concurrent radiation for head and neck squamous cell carcinoma.

BACKGROUND: Triweekly high-dose cisplatin (100 mg/m2 ) with concurrent radiation therapy is the current standard of care in the definitive or appropriate postoperative setting in head and neck squamous cell carcinoma (HNSCC). We compared triweekly 100 mg/m2 with alternative weekly 40 mg/m2 and weekly <40 mg/m2 cisplatin regimens. METHODS: From 2011 to 2016, 163 patients received concurrent cisplatin and intensity-modulated radiotherapy for locally advanced HNSCC. Primary endpoints were overall survival (OS) and progression-free survival. RESULTS: Cisplatin weekly <40 mg/m2 showed inferior OS outcomes when compared to weekly 40 mg/m2 (P = 0.084) and triweekly 100 mg/m2 (P = 0.04) regimens. CONCLUSION: Our study displayed inferior outcomes with weekly cisplatin doses under 40 mg/m2 , suggesting the inferiority of low-dose weekly chemotherapy and the need for ongoing randomized trials to further explore 40 vs 100 mg/m2 chemotherapy regimens.

Impact of Peer Review on Use of Hypofractionated Regimens for Early-Stage Breast Cancer for Patients at a Tertiary Care Academic Medical Center and Its Community-Based Affiliates.

PURPOSE: Data have demonstrated that hypofractionated radiation therapy (HFRT) and conventionally fractionated radiation therapy regimens are equivalent with respect to outcomes. Efforts to increase HFRT use have had mixed success. We implemented a prospective peer review chart rounds integrating all practice sites and reviewed the use of HFRT in an attempt to identify potential predictors of use. MATERIALS AND METHODS: Patients treated with whole-breast radiation therapy within our cancer care network from January 2016 to June 2017 were evaluated. Radiation courses with a dose per fraction of greater than 2 Gy were considered HFRT, whereas those with a dose per fraction of less than or equal to 2 Gy were considered as conventionally fractionated radiation therapy. Patient, provider, and tumor characteristics were categorized by use of HFRT and compared between groups using a χ2 test or two-tailed t test. RESULTS: A total of 349 consecutive patients were identified. All 120 patients treated at the main academic site received HFRT. There was significant variation in use of HFRT among community-based providers (28% to 100%; P < .001). There was increased use of HFRT after implementation of institution-wide prospective peer review (66% v 81% before and after implementation, respectively; P = .001). Age, tumor grade, chemotherapy receipt, surgeon type (academic v community), and treatment after implementation of peer review all correlated with HFRT use. On multivariable analysis, treatment after implementation of peer review ( P < .001) remained a significant predictor of HFRT use, as did age ( P = .005), tumor grade ( P = .013), and surgeon type ( P < .001). CONCLUSION: Significant variation persists in the use of HFRT among providers. Increased awareness and oversight through prospective peer review may be useful in improving compliance to HFRT. Expanding these efforts to include education of referring surgeons may be helpful.

Correlation of Acute and Late Brainstem Toxicities With Dose-Volume Data for Pediatric Patients With Posterior Fossa Malignancies.

PURPOSE: Radiation-induced brainstem toxicity after treatment of pediatric posterior fossa malignancies is incompletely understood, especially in the era of intensity modulated radiation therapy (IMRT). The rates of, and predictive factors for, brainstem toxicity after photon RT for posterior fossa tumors were examined. METHODS AND MATERIALS: After institutional review board approval, 60 pediatric patients treated at our institution for nonmetastatic infratentorial ependymoma and medulloblastoma with IMRT were included in the present analysis. Dosimetric variables, including the mean and maximum dose to the brainstem, the dose to 10% to 90% of the brainstem (in 10% increments), and the volume of the brainstem receiving 40, 45, 50, and 55 Gy were recorded for each patient. Acute (onset within 3 months) and late (>3 months of RT completion) RT-induced brainstem toxicities with clinical and radiographic correlates were scored using Common Terminology Criteria for Adverse Events, version 4.0. RESULTS: Patients aged 1.4 to 21.8 years underwent IMRT or volumetric arc therapy postoperatively to the posterior fossa or tumor bed. At a median clinical follow-up period of 2.8 years, 14 patients had developed symptomatic brainstem toxicity (crude incidence 23.3%). No correlation was found between the dosimetric variables examined and brainstem toxicity. Vascular injury or ischemia showed a strong trend toward predicting brainstem toxicity (P=.054). Patients with grade 3 to 5 brainstem toxicity had undergone treatment to significant volumes of the posterior fossa. CONCLUSION: The results of the present series demonstrate a low, but not negligible, risk of brainstem radiation necrosis for pediatric patients with posterior fossa malignancies treated with IMRT. No specific dose-volume correlations were identified; however, modern treatment volumes might help limit the incidence of severe toxicity. Additional work investigating inherent biologic sensitivity might also provide further insight into this clinical problem.

The Effect of Transition Clinics on Knowledge of Diagnosis and Perception of Risk in Young Adult Survivors of Childhood Cancer.

BACKGROUND: Improved treatment for pediatric cancers has ensured an evergrowing population of patients surviving into adulthood. The current study evaluated the impact of previous engagement in survivor care on patient knowledge and awareness of health risks as young adults. PROCEDURE: Young adult survivors of childhood cancers (N=93, M age=23.63 y) were recruited during their annual survivor clinic visit. Participants completed self-reported measures of demographics, treatment knowledge, perception of future health risks, participation in previous survivor care, and neurocognitive functioning. RESULTS: In total, 82% of patients (N=76/93) reported previously participating in survivorship care. These patients were more likely to have knowledge of their radiation treatment (P=0.034) and more likely to recognize risk for future health effects from their treatment (P=0.019). Income between $10,000 and $24,999 (odds ratio=0.168; 95% confidence interval, 0.046-0.616; P=0.031) was associated with decreased patient knowledge regarding diagnosis. Male sex (odds ratio=0.324; 95% confidence interval, 0.135-0.777; P=0.012) was associated with less knowledge of future health risks. Patients with self-reported difficulties on the CCSS-NCQ were more likely to regard their cancer treatment as a future health risk. CONCLUSION: Participation in survivor care plays an important role in imparting information to young adult survivors of pediatric cancer regarding their disease history and risk for future health problems.