Higher Reported Lung Dose Received During Total Body Irradiation for Allogeneic Hematopoietic Stem Cell Transplantation in Children With Acute Lymphoblastic Leukemia Is Associated With Inferior Survival: A Report from the Children's Oncology Group.

PURPOSE: To examine the relationship between lung radiation dose and survival outcomes in children undergoing total body irradiation (TBI)-based hematopoietic stem cell transplantation (HSCT) for acute lymphoblastic leukemia on the Children's Oncology Group trial. METHODS AND MATERIALS: TBI (1200 or 1320 cGy given twice daily in 6 or 8 fractions) was used as part of 3 HSCT preparative regimens, allowing institutional flexibility regarding TBI techniques, including lung shielding. Lung doses as reported by each participating institution were calculated for different patient setups, with and without shielding, with a variety of dose calculation techniques. The association between lung dose and transplant-related mortality, relapse-free survival, and overall survival (OS) was examined using the Cox proportional hazards regression model controlling for the following variables: TBI dose rate, TBI fields, patient position during TBI, donor type, and pre-HSCT minimal residual disease level. RESULTS: Of a total of 143 eligible patients, 127 had lung doses available for this analysis. The TBI techniques were heterogeneous. The mean lung dose was reported as 904.5 cGy (standard deviation, ±232.3). Patients treated with lateral fields were more likely to receive lung doses ≥800 cGy (P < .001). The influence of lung dose ≥800 cGy on transplant-related mortality was not significant (hazard ratio [HR], 1.78; P = .21). On univariate analysis, lung dose ≥800 cGy was associated with inferior relapse-free survival (HR, 1.76; P = .04) and OS (HR, 1.85; P = .03). In the multivariate analysis, OS maintained statistical significance (HR, 1.85; P = .04). CONCLUSIONS: The variability in TBI techniques resulted in uncertainty with reported lung doses. Lateral fields were associated with higher lung dose, and thus they should be avoided. Patients treated with lung dose <800 cGy in this study had better outcomes. This approach is currently being investigated in the Children's Oncology Group AALL1331 study. Additionally, the Imaging and Radiation Oncology Core Group is evaluating effects of TBI techniques on lung doses using a phantom.

Gamma Knife Stereotactic Radiosurgery for Grade 2 Meningiomas.

Purpose This study aims to report long-term clinical outcomes after Gamma Knife radiosurgery (GKRS) for intracranial grade 2 meningiomas. Methods In this Institutional Review Board approved study, we reviewed records of all patients with grade 2 meningiomas treated with GKRS between 1998 and 2014. Results A total of 97 postoperative histopathologically confirmed grade 2 meningiomas in 75 patients were treated and are included in this study. After a mean follow-up of 41 months, 28 meningiomas had local recurrence (29.79%). Median time to local recurrence was 89 months (mean: 69, range: 47-168). The 3- and 5-year actuarial local control (LC) rates were 68.9 and 55.7%, respectively. The 3- and 5-year overall survival rates were 88.6 and 81.1%, respectively. There was a trend toward worse LC with tumors treated with radiation doses ≤ 13 versus > 13 Gy. There was no radiation necrosis or second malignant tumors noted in our series. Conclusion This report, one of the largest GKRS series for grade 2 meningiomas, demonstrates that GKRS is a safe and effective treatment modality for patients with grade 2 meningiomas with durable tumor control and minimal toxicity. Adjuvant GKRS could be considered as a reasonable treatment approach for patients with grade 2 meningiomas.

Thyroid V50 Highly Predictive of Hypothyroidism in Head-and-Neck Cancer Patients Treated With Intensity-modulated Radiotherapy (IMRT).

OBJECTIVES: Radiation-induced hypothyroidism affects a significant number of patients with head-and-neck squamous cell cancer (HNSCC). We examined detailed dosimetric and clinical parameters to better determine the risk of hypothyroidism in euthyroid HNSCC patients treated with intensity-modulated radiation therapy (IMRT). MATERIALS AND METHODS: From 2006 to 2010, 75 clinically euthyroid patients with HNSCC were treated with sequential IMRT. The cohort included 59 men and 16 females with a median age of 55 years (range, 30 to 89 y) who were treated to a median dose of 70 Gy (range, 60 to 75 Gy) with concurrent chemotherapy in nearly all (95%) cases. Detailed thyroid dosimetric parameters including maximum dose, mean dose, and other parameters (eg, V50-percent volume receiving at least 50 Gy) were obtained. Freedom from hypothyroidism was evaluated using the Kaplan-Meier method. Univariate and multivariate analyses were conducted using Cox regression. RESULTS: After a median follow-up period of 50 months, 25 patients (33%) became hypothyroid. On univariate analysis, thyroid V50 was highly correlated with developing hypothyroidism (P=0.035). Other dosimetric paramaters including mean thyroid dose (P=0.11) and maximum thyroid dose (P=0.39) did not reach statistical significance. On multivariate analysis incorporating patient, tumor, and treatment variables, V50 remained highly statistically significant (P=0.037). Regardless of other factors, for V50>60%, the odds ratio of developing hypothyroidism was 6.76 (P=0.002). CONCLUSIONS: In HNSCC patients treated with IMRT, thyroid V50 highly predicts the risk of developing hypothyroidism. V50>60% puts patients at a significantly higher risk of becoming hypothyroid. This can be a useful dose constraint to consider during treatment planning.

Low-Dose-Rate Brachytherapy Boosting Concurrent Chemoradiation as a Definitive Treatment Modality for Cervical Cancer: Long-term Clinical Results of Outcomes and Associated Toxicity.

PURPOSE: To review and report the long-term treatment-induced adverse events (AEs) and outcomes of concomitant chemoradiotherapy boosted by low-dose-rate (LDR) conventional brachytherapy (BT) planning in patients with locoregionally advanced cervical cancer. PATIENTS AND METHODS: After obtaining institutional review board approval, we reviewed the records of patients with stage IB1 to IVA, intact cervical cancer who were treated at our institution between 1983 and 2009. Eligible patients underwent definitive radiotherapy with external-beam radiation concomitant with cisplatin-based chemotherapy and boosted by LDR BT. Patient, tumor, and treatment characteristics; treatment-induced AEs, namely, gastrointestinal and genitourinary toxicities, as well as treatment outcomes; locoregional control (LRC), distant control (DC), progression-free survival (PFS), and overall survival (OS) were reviewed and reported. RESULTS: The study included 129 eligible cervical cancer patients; the median age was 46 years (mean, 47 ± 11 y; range, 28 to 81 y), consisting of stages I, II, III, and IV (29.5%, 48.1%, 17.8%, and 4.6%, respectively). The median follow-up was 37 months (mean, 58 ± 59 mo; range, 3 to 275 mo). The 3-year OS, PFS, LRC, and DC were 75.9%, 71.6%, 84.7%, and 80.2%, respectively. The 5-year OS, PFS, LRC, and DC were 70.7%, 68.7%, 84.7%, and 78.3%, respectively. The 10-year OS, PFS, LRC, and DC were 68.7%, 62.3%, 82.5%, and 73.2%, respectively. Gastrointestinal and genitourinary grade 3 and 4 acute AEs were reported in 3.9% and 0%, and chronic grade 3 and 4 AEs were reported in 20.9% and 12.4% of all patients, respectively. CONCLUSIONS: Definitive chemoradiotherapy followed by conventional LDR BT boost is effective, feasible, and tolerable treatment modality for cervical cancer. A comparison with MRI image-guided BT shows comparable treatment outcomes with superior OS in favor of LDR BT but inferior LC with a relatively worse toxicity profile.

Contouring Guidelines for the Axillary Lymph Nodes for the Delivery of Radiation Therapy in Breast Cancer: Evaluation of the RTOG Breast Cancer Atlas.

PURPOSE: The purpose of this study was to identify the axillary lymph nodes on pretreatment diagnostic computed tomography (CT) of the chest to determine their position relative to the anatomic axillary borders as defined by the Radiation Therapy Oncology Group (RTOG) breast cancer atlas for radiation therapy planning. METHODS AND MATERIALS: Pretreatment diagnostic CT chest scans available for 30 breast cancer patients with clinically involved lymph nodes were fused with simulation CT. Contouring of axillary levels I, II, and III according to the RTOG guidelines was performed. Measurements were made from the area of distal tumor to the anatomic borders in 6 dimensions for each level. RESULTS: Of the 30 patients, 100%, 93%, and 37% had clinical involvement of levels I, II, and III, respectively. The mean number of lymph nodes dissected was 13.6. The mean size of the largest lymph node was 2.4 cm. Extracapsular extension was seen in 23% of patients. In 97% of patients, an aspect of the involved lymph node lay outside of the anatomic border of a level. In 80% and 83% of patients, tumor extension was seen outside the cranial (1.78 ± 1.0 cm; range, 0.28-3.58 cm) and anterior (1.27 ± 0.92 cm; range, 0.24-3.58 cm) borders of level I, respectively. In 80% of patients, tumor extension was seen outside the caudal border of level II (1.36 ± 1.0 cm, range, 0.27-3.86 cm), and 0% to 33% of patients had tumor extension outside the remaining borders of all levels. CONCLUSIONS: To cover 95% of lymph nodes at the cranial and anterior borders of level I, an additional clinical target volume margin of 3.78 cm and 3.11 cm, respectively, is necessary. The RTOG guidelines may be insufficient for coverage of axillary disease in patients with clinical nodal involvement who are undergoing neoadjuvant chemotherapy, incomplete axillary dissection, or treatment with intensity modulated radiation therapy. In patients with pretreatment diagnostic CT chest scans, fusion with simulation CT should be considered for tumor delineation.

Hyperthermia and radiation therapy for locally advanced or recurrent breast cancer.

INTRODUCTION: This study aims to report the outcome and toxicity of combined hyperthermia (HT) and radiation therapy (RT) in treatment of locally advanced or loco-regionally recurrent breast cancer. PATIENTS AND METHODS: Patients treated with HT and RT from January 1991 to December 2007 were reviewed. RT doses for previously irradiated patients were > 40 Gy and for RT naïve patients > 60 Gy, at 1.8-2 Gy/day. HT was planned for 2 sessions/week, immediately after RT, for a minimum of 20 min and for > 4 sessions. Superficial or interstitial applicators were used with temperature measured by superficial or interstitial thermistors based on target thickness. HT treatment was assessed by thermal equivalent dose (TED), > 42.5 °C and > 43 °C. Endpoints included treatment response, lack of local progression (local control), and survival. RESULTS: 127 patients received HT and RT to 167 sites. These included the intact breast (24.4%), chest wall/skin (67.7%), and breast/chest wall and nodes (7.9%). At a median follow-up of 13 months (mean 30 ± 38), improved overall survival was significantly associated with increasing RT dose (p < 0.0001), median TED 42.5 °C ≥ 200 min (p = 0.003), and local control (p = 0.0002). Local control at last follow-up was seen in 55.1% of patients. Complete response was significantly associated with median TED 42.5 °C ≥ 200 min (p = 0.002) and median TED 43 °C ≥ 100 min (p = 0.03). CONCLUSION: HT and RT are effective for locally advanced or recurrent breast cancer in patients that have been historically difficult to treat by RT alone. Over 50% of patients achieved control of locoregional disease. Overall survival was improved with local control.

Age most significant predictor of requiring enteral feeding in head-and-neck cancer patients.

BACKGROUND: A significant number of patients treated for head and neck squamous cell cancer (HNSCC) undergo enteral tube feeding. Data suggest that avoiding enteral feeding can prevent long-term tube dependence and disuse of the swallowing mechanism which has been linked to complications such as prolonged dysphagia and esophageal constriction. We examined detailed dosimetric and clinical parameters to better identify those at risk of requiring enteral feeding. METHODS: One hundred patients with advanced stage HNSCC were retrospectively analyzed after intensity-modulated radiation therapy (IMRT) to a median dose of 70 Gy (range: 60-75 Gy) with concurrent chemotherapy in nearly all cases (97%). Patients with significant weight loss (>10%) in the setting of severely reduced oral intake were referred for placement of a percutaneous endoscopic gastrostomy (PEG) tube. Detailed DVH parameters were collected for several structures. Univariate and multivariate analyses using logistic regression were used to determine clinical and dosimetric factors associated with needing enteral feeding. Dichotomous outcomes were tested using Fisher's exact test and continuous variables between groups using the Wilcoxon rank-sum test. RESULTS: Thirty-three percent of patients required placement of an enteral feeding tube. The median time to tube placement was 25 days from start of treatment, after a median dose of 38 Gy. On univariate analysis, age (p=0.0008), the DFH (Docetaxel/5-FU/Hydroxyurea) chemotherapy regimen (p= .042) and b.i.d treatment (P=0.040) (used in limited cases on protocol) predicted need for enteral feeding. On multivariate analysis, age remained the single statistically significant factor (p=0.003) regardless of other clinical features (e.g. BMI) and all radiation planning parameters. For patients 60 or older compared to younger adults, the odds ratio for needing enteral feeding was 4.188 (p=0.0019). CONCLUSIONS: Older age was found to be the most significant risk factor for needing enteral feeding in patients with locally advanced HNSCC treated with multimodal treatment. Pending further validation, this would support maximizing early nutritional guidance, targeted supplementation, and symptomatic support for older adults (>60) undergoing chemoradiation. Such interventions and others (e.g. swallowing therapy) could possibly delay or minimize the use of enteral feeding, thereby helping avoid tube dependence and tube-associated long-term physiologic consequences.

Whole-Field Sequential Intensity-Modulated Radiotherapy for Local-Regional Advanced Head-and-Neck Squamous Cell Carcinoma.

PURPOSE: There is little published data on the technique and results of whole-field (WF) sequential intensity-modulated radiotherapy (S-IMRT) for patients with head-and-neck squamous cell carcinoma (HNSCC). We report the treatment outcomes, adverse events (AEs), and dosimetric parameters in local-regional advanced (LRA) HNSCC patients treated with the WF S-IMRT technique. METHODS: The IRB approved this retrospective study. Patients received WF S-IMRT with or without concomitant chemotherapy. Three separate IMRT plans corresponding to 3 planning target volumes were generated. This study reports patient and tumor characteristics, treatment-induced acute AEs based on CTCAE version 3.0, chronic AEs according to RTOG scale and treatment outcomes, local-regional control (LRC), distant metastases (DM), relapse-free survival (RFS), and overall survival (OS). RESULTS: Between January 2003 and December 2010, 103 patients with LRA HNSCC were treated either definitively or postoperatively with WF S-IMRT, with (99 patients) or without (4 patients) concurrent chemotherapy. The median age was 55 years (range, 30 to 89 y). The median cumulative target dose was 70 Gy (range, 60 to 75 Gy). At a median follow-up of 40 months (range, 4 to 95 mo), the 2- and 5-year rates of OS were 94% and 77%, RFS were 90% and 84%, LRC were 97% and 93%, and DM were 9% and 11%, respectively. Grade 3 acute AEs included mucositis (68%), dysphagia (35%), weight loss (19.6%), and xerostomia (7.8%). Chronic worst grade 3 AEs included xerostomia (21.9%), weight loss (12.8%), and dysphagia (12.5%). Chronic grade 3 AEs at last follow-up included weight loss (6.25%), dysphagia (6.2%), and xerostomia (6.2%). No patient had an acute or chronic grade 4 AE, brachial plexopathy, or spinal cord injury. CONCLUSIONS: WF S-IMRT results in excellent tumor control and an acceptable toxicity profile in LRA HNSCC patients treated with this technique.