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IntroductionA broad range of stakeholders have called for randomised evidence on the potential clinical benefits and harms of proton therapy, a type of radiation therapy, for patients with breast cancer. Radiation therapy is an important component of curative treatment, reducing cancer recurrence and extending survival. Compared with photon therapy, the international treatment standard, proton therapy reduces incidental radiation to the heart. Our overall objective is to evaluate whether the differences between proton and photon therapy cardiac radiation dose distributions lead to meaningful reductions in cardiac morbidity and mortality after treatment for breast cancer.MethodsWe are conducting a large scale, multicentre pragmatic randomised clinical trial for patients with breast cancer who will be followed longitudinally for cardiovascular morbidity and mortality, health-related quality of life and cancer control outcomes. A total of 1278 patients with non-metastatic breast cancer will be randomly allocated to receive either photon or proton therapy. The primary outcomes are major cardiovascular events, defined as myocardial infarction, coronary revascularisation, cardiovascular death or hospitalisation for unstable angina, heart failure, valvular disease, arrhythmia or pericardial disease. Secondary endpoints are urgent or unanticipated outpatient or emergency room visits for heart failure, arrhythmia, valvular disease or pericardial disease. The Radiotherapy Comparative Effectiveness (RadComp) Clinical Events Centre will conduct centralised, blinded adjudication of primary outcome events.Ethics and disseminationThe RadComp trial has been approved by the institutional review boards of all participating sites. Recruitment began in February 2016. Current version of the protocol is A3, dated 08 November 2018. Dissemination plans include presentations at scientific conferences, scientific publications, stakeholder engagement efforts and presentation to the public via lay media outlets.Trial registration numberNCT02603341

Soft tissue sarcomas (STS) are rare solid tumors of mesenchymal cell origin that display a heterogenous mix of clinical and pathologic characteristics. STS can develop from fat, muscle, nerves, blood vessels, and other connective tissues. The evaluation and treatment of patients with STS requires a multidisciplinary team with demonstrated expertise in the management of these tumors. The complete NCCN Guidelines for Soft Tissue Sarcoma (available at NCCN.org) provide recommendations for the diagnosis, evaluation, and treatment of extremity/superficial trunk/head and neck STS, as well as intra-abdominal/retroperitoneal STS, gastrointestinal stromal tumor, desmoid tumors, and rhabdomyosarcoma. This manuscript discusses guiding principles for the diagnosis and staging of STS and evidence for treatment modalities that include surgery, radiation, chemoradiation, chemotherapy, and targeted therapy.

Background The purpose of this study was to evaluate the efficacy and tolerability of the addition of 2 monoclonal antibodies, bevacizumab and cetuximab, to 2 cycles of high-dose cisplatin administered concurrently with intensity-modulated radiation therapy (IMRT) for head and neck squamous cell carcinoma (HNSCC). Methods Patients with newly diagnosed stage III/IVB (M0) HNSCC received cetuximab (400 mg/m2 loading dose, followed by 250 mg/m2 weekly), bevacizumab (15 mg/kg, days 1 and 22), and cisplatin (50 mg/m2, days 1, 2, 22, and 23) concurrently with IMRT (70 Gy). The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS) and safety and tolerability. Results Among 30 patients enrolled in this study, the primary tumor site was the oropharynx in 24 patients (p16 immunohistochemistry was positive in 17, negative in 1, and not done in 6 of the oropharyngeal tumors). Median age was 57 years (range, 38–77 years) and 27 patients had clinical stage IVA disease. All patients completed the full planned dose of radiation therapy. The most common ≥ grade 3 adverse events were lymphopenia, mucositis (functional), and dysphagia. With a median follow-up of 33.8 months, 2-year PFS was 88.5% (95% confidence interval [CI] = 68.1–96.1) and 2-year OS was 92.8% (95% CI = 74.2–98.1). Conclusion The addition of bevacizumab and cetuximab to 2 cycles of cisplatin, given concurrently with IMRT, was well-tolerated and was associated with favorable efficacy outcomes in this patient population. © 2015 Wiley Periodicals, Inc. Head Neck, 2015

Background The purpose of this study was to examine patterns of failure and the relationship to radiation doses in patients with head and neck carcinoma of unknown primary (HNCUP). Methods We reviewed 85 patients with HNCUP treated with curative-intent radiation therapy (RT) during 1995 to 2012. Results There have been no failures in the pharyngeal axis. Relapse at initial neck sites of disease developed in 7 patients (8.2%). The median dose to these sites was 70 Gy (range, 63–70 Gy). Failure at neck sites without initial disease occurred in 4 patients (4.7%). The median dose was 54 Gy (range, 50–58.8 Gy). There were no contralateral failures in a small cohort of patients receiving unilateral treatment (n = 6). Percutaneous endoscopic gastrostomy (PEG) tube dependence at 12 months was 7.4%, and 2.5% at 3 years. Esophageal stricture developed in 5 patients (5.9%). Conclusion RT for HNCUP produces excellent locoregional control rates with acceptably low levels of late toxicity. Doses prescribed to sites of eventual failure did not vary significantly from those sites that were treated and remain in control. © 2015 Wiley Periodicals, Inc. Head Neck 38: E426–E431, 2016

Gastrointestinal stromal tumors (GIST) are the most common soft tissue sarcoma of the gastrointestinal tract, resulting most commonly from KIT or platelet-derived growth factor receptor α (PDGFRα)-activating mutations. These NCCN Guideline Insights highlight the important updates to the NCCN Guidelines for Soft Tissue Sarcoma specific to the management of patients with GIST experiencing disease progression while on imatinib and/or sunitinib.

These NCCN Guidelines Insights highlight the important updates to the NCCN Guidelines for Soft Tissue Sarcoma (STS) specific to the role of radiation therapy in the management of patients with retroperitoneal/intra-abdominal STS. The guidelines have also included recommendations for genetic testing and counseling for patients with a clinical and/or family history of genetic cancer syndromes associated with a predisposition for the development of STS.

Recent studies have demonstrated that per-beam planar intensity-modulated radiation therapy (IMRT) quality assurance (QA) passing rates may not predict clinically relevant patient dose errors. This work is to evaluate the effect of dose variations introduced in dynamic multileaf collimator (DMLC) modeling and delivery processes on clinically relevant metrics for IMRT. Ten head and neck (HN) IMRT plans were randomly selected for this study. The conventional per-beam IMRT QA was performed for each plan by 2 different methods: (1) with gantry angle of 0 (gantry pointing downward) for all IMRT fields and (2) with gantry at specific angles as designed in the IMRT plan. For each patient, a batch analysis was done for each scenario and then imported to the 3DVH (Sun Nuclear Corp.) for processing. A “corrected DVH” was generated and compared to the DVH from the treatment plan. Their differences represented errors introduced from the combination of the treatment planning system (TPS) dose calculation algorithm and beam-delivery. The dose metrics from the two scenarios were compared with the corresponding calculated doses, and then their differences were analyzed. Although all per-beam planar IMRT QA had high Gamma passing rates 99.3 ± 1.3% (92.3–100%) for “2%/3 mm” criteria, there were significant errors in some of the calculated clinical dose metrics. Such as, for all the plans studied, there were as much as 3.2%, 5.7%, 5.6%, 2.3%, 4.1%, and −3.8% errors found in max cord dose, max brainstem dose, mean parotid dose, larynx dose, oral cavity dose, and PTV(D95) dose, respectively. The differences in errors for clinical metrics obtained between the two scenarios (zero gantry angle vs. true gantry angles) can also be significant: max cord dose (2.9% vs. 0.2%), max brainstem dose (3.8% vs. 0.4%), mean parotid dose (2.3% vs. 4.5%), mean larynx dose (3.9% vs. 2.0%), mean oral cavity dose (1.6% vs. 3.9%), and PTV(D95) dose (−0.4% vs. −2.6%). However, in the two scenarios, a strong and clear correlation between the dose differences for each of the organ structures was observed. This study confirms that conventional IMRT QA performance metrics are not predictive of dose errors in PTV and organs-at-risk. The clinically-relevant-dose QA has allowed us to predict the patient dose-volume relationships.

In this study, we verified the treatment planning calculations of skin doses with the incorporation of the bolus effect due to the intervening alpha-cradle (AC) and carbon fiber couch (CFC) using radiochromic EBT2 films. A polystyrene phantom (25 × 25 × 15 cm3) with six EBT2 films separated by polystyrene slabs, at depths of 0, 0.1, 0.2, 0.5, 1, 1.4 cm, was positioned above an AC, which was ~1 cm thick. The phantom and AC assembly were CT scanned and the CT-images were transferred to the treatment planning system (TPS) for calculations in three scenarios: (A) ignoring AC and CFC, (B) accounting for AC only, (C) accounting for both AC and CFC. A single posterior 10 × 10 cm2 field, a pair of posterior-oblique 10 × 10 cm2 fields, and a posterior IMRT field (6 MV photons from a Varian Trilogy linac) were planned. For each radiation field configuration, the same MU were used in all three scenarios in the TPS. Each plan for scenario C was delivered to expose a stack of EBT2 films in the phantom through AC and CFC. In addition, in vivo EBT2 film measurement on a lung cancer patient immobilized with AC undergoing IMRT was also included in this study. Point doses and planar distributions generated from the TPS for the three scenarios were compared with the data from the EBT2 film measurements. For all the field arrangements, the EBT2 film data including the in vivo measurement agreed with the doses calculated for scenario (C), within the uncertainty of the EBT2 measurements (~4%). For the single posterior field (a pair of posterior-oblique fields), the TPS generated doses were lower than the EBT2 doses by 34%, 33%, 31%, 13% (34%, 31%, 31%, 11%) for scenario A and by 27%, 25%, 22%, 8% (25%, 21%, 21%, 6%) for scenario B at the depths of 0, 0.1, 0.2, 0.5 cm, respectively. For the IMRT field, the 2D dose distributions at each depth calculated in scenario C agree with those measured data. When comparing the central axis doses for the IMRT field, we found the TPS generated doses for scenario A (B) were lower than the EBT2 data by 35%, 34%, 31%, 16% (29%, 26%, 23%, 10%) at the depths of 0, 0.1, 0.2, 0.5 cm, respectively. There were no significant differences for the depths of 1.0 and 1.4 cm for all the radiation fields studied. TPS calculation of doses in the skin layers accounting for AC and CFC was verified by EBT2 film data. Ignoring the presence of AC and/or CFC in TPS calculation would significantly underestimate the doses in the skin layers. For the clinicians, as more hypofractionated regimens and stereotactic regimens are being used, this information will be useful to avoid potential serious skin toxicities, and also assist in clinical decisions and report these doses accurately to relevant clinical trials/cooperative groups, such as RTOG.

The major changes to the 2012 and 2011 NCCN Guidelines for Soft Tissue Sarcoma pertain to the management of patients with gastrointestinal stromal tumors (GISTs) and desmoid tumors (aggressive fibromatosis). Postoperative imatinib following complete resection for primary GIST with no preoperative imatinib is now included as a category 1 recommendation for patients with intermediate or high risk of recurrence. The panel also reaffirmed the recommendation for preoperative use of imatinib in patients with GISTs that are resectable with negative margins but associated with significant surgical morbidity. Observation was included as an option for patients with resectable desmoid tumors that are small and asymptomatic, not causing morbidity, pain, or functional limitation. Sorafenib is included as an option for systemic therapy for patients with desmoid tumors.

BACKGROUND: The clinical benefit of routine placement of prophylactic percutaneous endoscopic gastrostomy (pPEG) tubes was assessed in patients with oropharyngeal cancer (OPC) who are undergoing intensity-modulated radiotherapy (IMRT) with concurrent chemotherapy. METHODS: From 1998 through 2009, 400 consecutive patients with OPC who underwent chemoradiation were included. Of these, 325 had a pPEG and 75 did not (nPEG). Weight and albumin change from baseline to mid-IMRT, end of IMRT, 1 month post-IMRT, and 3 months post-IMRT were evaluated. The treating physicians prospectively recorded acute and late toxicities. RESULTS: Significantly lower absolute weight loss at end of IMRT (6.80 kg vs 8.38 kg, P = .007), 1 month post-IMRT (9.06 kg vs 11.33 kg, P = .006), and 3 months post-IMRT (11.10 kg vs 13.09 kg, P = .044) was noted in the pPEG versus nPEG groups. This benefit in reduction of percent weight loss was consistently significant only among patients with BMI 55 years (P < .001), female sex (P < .001), and T3/4 category disease (P < .001) were significantly associated with prolonged PEG use. CONCLUSIONS: Although pPEG reduced absolute and percent weight loss and need for hospitalizations in our cohort of patients with OPC undergoing chemoradiation, no differences were noted in radiation treatment duration, toxicity, and overall survival. Prolonged PEG use correlated with age >55 years, female sex, and T3/T4 tumors. Cancer 2012. © 2012 American Cancer Society.

Purpose: To evaluate the measured dose distributions using radiochromic EBT2 films for small fields in iPlan (BrainLab) commissioning. Methods: Radiochromic EBT2 films were irradiated with 6 MV photons on a Varian Trilogy linac using polystyrene phantoms. The measurements included dose profiles and depth doses for field sizes of 1 × 1, 2 × 2, 3 × 3, 4 × 4, and 10 × 10 cm 2 etc. The dose profile measurements were taken at the depth of 5 cm. The calibration films were irradiated at dmax(1.4 cm) for doses up to 6 Gy. Films were scanned using an Epson 10,000 XL flatbed scanner with 72 dpi resolution. Pixel values were converted to doses using the established calibration-curve. The 2D dose distributions were generated from the film data analysis. In-house software was utilized to compare the measured doses from films with the treatment planning data. In addition, selected patients’ SRS fields were also measured with the EBT2 films for comparison with iPlan. An EDGE TM detector was also used to check the central-axis doses for the SRS patients’ measurements. Results and Discussion: The measured planar dose distributions achieved more than 98% and 95% passing rates with a set of 2%/2 mm dose and DTA criteria for all square fields and all patient treatment fields (

ObjectivesTo assess whether sparing neck-level IB in target delineation of node-positive (N+) oropharyngeal carcinoma (OPC) can improve xerostomia outcomes without compromising locoregional control (LRC).MethodsA total of 125 N+ OPC patients with a median age of 57 years underwent chemoradiation between May 2010 and December 2011. A total of 74% of patients had T1-T2 disease, 26% T3-T4, 16% N1, 8% N2A, 48% N2B, 28% N2C; 53% base of tongue, 41% tonsil, and 6% other. Patients were divided into those who had target delineation sparing of bilateral level IB (the spared cohort) versus no sparing (the treated cohort). Sparing of contralateral high-level II nodes was also performed more consistently in the spared cohort. A prospective xerostomia questionnaire (patient reported) was given at each patient follow-up visit to this cohort of patients to assess late xerostomia. Clinical assessment (observer rated) at each patient follow-up visit was also recorded.ResultsThe 2-year LRC for the spared and treated cohorts was 97.5% and 93.8%, respectively (median follow-up, 23.2 mo). No locoregional failures occurred outside of treatment fields. The spared cohort experienced significant benefits in patient-reported xerostomia summary scores (P=0.021) and observer-rated xerostomia scores (P=0.006). In addition, there were significant reductions in mean doses to the ipsilateral submandibular gland (63.9 vs. 70.5 Gy; P

This study was designed to assess the feasibility and potential benefit of using intensity-modulated radiotherapy (IMRT) planning for patients newly diagnosed with glioblastoma multiforme (GBM). Five consecutive patients with confirmed histopathologically GBM were entered into the study. These patients were planned and treated with 3-dimensional conformal radiation therapy (3DCRT) using our standard plan of 3 noncoplanar wedged fields. They were then replanned with the IMRT method that included a simultaneous boost to the gross tumor volume (GTV). The dose distributions and dose-volume histograms (DHVs) for the planning treatment volume (PTV), GTV, and the relevant critical structures, as obtained with 3DCRT and IMRT, respectively, were compared. In both the 3DCRT and IMRT plans, 59.4 Gy was delivered to the GTV plus a margin of 2.5 cm, with doses to critical structures below the tolerance threshold. However, with the simultaneous boost in IMRT, a higher tumor dose of approximately 70 Gy could be delivered to the GTV, while still maintaining the uninvolved brain at dose levels of the 3DCRT technique. In addition, our experience indicated that IMRT planning is less labor intensive and time consuming than 3DCRT planning. Our study shows that IMRT planning is feasible and efficient for radiotherapy of GBM. In particular, IMRT can deliver a simultaneous boost to the GTV while better sparing the normal brain and other critical structures.

Purpose: To assess the patterns of failure for patients with medulloblastoma receiving a conformal tumor bed boost rather than a boost to the entire posterior fossa. Patients and Methods: From 1994 to 2002, 32 consecutive patients with newly diagnosed medulloblastoma treated at Memorial Sloan-Kettering Cancer Center (New York, NY) received a conformal boost to the tumor bed in conjunction with craniospinal radiation therapy. Twenty-eight patients also received chemotherapy. The median age was 9 years (range, 3 to 34 years), and the male to female ratio was 3:1. Twenty-seven patients had standard-risk disease, and five patients had high-risk disease. Craniospinal doses ranged from 23.4 to 39.6 Gy, and total tumor bed doses ranged from 54 to 59.4 Gy. Results: With a median follow-up of 56 months, six patients have relapsed; five relapsed outside of the posterior fossa, and one failed within the posterior fossa, outside of the high-dose boost volume. Five-year actuarial disease-free and overall survival rates were 84% and 85%, respectively. Freedom from posterior fossa failure was 100% and 86% at 5 and 10 years, respectively. Freedom from distant failure was 84% at 5 years, with a trend for improvement when full-dose craniospinal radiation (36 to 39.6 Gy) was used compared with a reduced dose (23.4 Gy) of radiation (100% v 63%, respectively; P = .06). No other predictive variables were identified. Conclusion: Conformal treatment to the tumor bed allows for significant sparing of critical structures. The posterior fossa failure rate in this series is similar to that reported when the entire posterior fossa is treated. This approach should be investigated further in a phase III trial.

An iterative algorithm has been developed to analytically determine patient specific input parameters for intensity‐modulated radiotherapy prostate treatment planning. The algorithm starts with a generic set of inverse planning parameters that include dose and volume constraints for the target and surrounding critical structures. The overlap region between the target volume and the rectum is used to determine the optimized target volume coverage goal. Sequential iterations are performed to vary the numerous parameters individually or in sets while other parameters remain fixed. A coarse grid search is first used to avoid convergence on a local maximum. Linear interpolation is then used to define a region for a fine grid search. Selected parameters are also tested for possible improvements in target coverage. In several representative test cases investigated the coverage of the planning target volume improved with the use of the algorithm while still meeting the clinical acceptability criteria for critical structures. The algorithm avoids time‐consuming random trial and error variations that are often associated with difficult cases and also eliminates lengthy user learning curves. The methodology described in this paper can be applied to any treatment planning system that requires the user to select the input optimization parameters. PACS number(s): 87.53.–j, 87.90.+y

6076 Background: We conducted a pilot study using functional imaging to guide reduction in radiation (RT) to 30Gy with concurrent chemotherapy in patients with HPV+ OPC. Methods: 19 patients were enrolled prospectively from 7/2015-10/2016. Primary tumors were excised and analyzed for DNA repair foci ex-vivo. A pre-RT dynamic 18F-FMISO (fluoromisonidazole) PET was then used to assess tumor hypoxia (defined as > 1.2 tumor to muscle SUV ratio) in cervical lymph nodes. Patients without hypoxia on baseline or repeat scan done 5-10 days after initiation of chemoRT received 30Gy (57% reduction) over 3 weeks to the tumor bed and neck with 2 cycles of concurrent chemotherapy (high-dose cisplatin or carboplatin/5-FU). Patients with persistent hypoxia received the standard dose of 70Gy over 7 weeks with chemo. Neck dissection (ND) was done 4-months post chemoRT. Weekly DWI MRI, ctDNA, whole exome & RNA sequencing were performed. Results: 19 patients (11 tonsil, 5 BoT, 3 unknown primaries) were enrolled. Staging: 11 T1, 5 T2, 3 Tx; 5 N1, 3 N2a, 11 N2b; all M0. On pre-RT 18F-FMISO scans, 13 were positive and 6 were negative for hypoxia. Of the 12 intra-treatment 18F-FMISO scans (1 not done due to intermittent illness, this patient received 70Gy), 3 were positive and these patients received 70Gy chemoRT. 15 patients were de-escalated to 30Gy. To date, analysis showed complete pathologic response in 8 of 9 patients (all 15 expected to have ND by April 2017. The one positive case received only 1 cycle of cisplatin. To date, 18 of 19 patients (95%-6 pending ND) remain disease free. Correlative analysis with sequencing, DNA repair foci, ctDNA, and results from pathologic and intra-treatment imaging response will be presented. Conclusions: This is the first report of apersonalized approach to a major decrease in RT dosing for definitive treatment of HPV+ oropharyngeal carcinoma guided by patient-specific imaging-based treatment response. De-escalation to 30Gy informed by intra-treatment imaging for hypoxia appears feasible, safe and efficacious. A multi-center trial to validate these pilot results is planned. Clinical trial information: NCT00606294.

Extraskeletal chondrosarcoma of the leg is a rare, malignant neoplasm with very few cases having been reported in the literature. In this study we investigate the possibility of using intensity modulated radiotherapy (IMRT) for this type of disease and demonstrate its advantages over conventional three-dimensional (3D) conformal treatment. A case was presented of a patient with extraskeletal chondrosarcoma of the lateral compartment of the leg in which the target volume was 50 cm in length and twisted around the surrounding bones. Both the 3D conformal plan and IMRT plan were designed using the Memorial Sloan-Kettering Cancer Center planning system. The IMRT plan produced a superior dose distribution to the patient as compared to the 3D conformal plan both in terms of dose conformity and homogeneity in the target volumes, and reduction of the maximum dose to the bone. The planning time of the IMRT plan was about 35 times shorter than that of the 3D conformal plan. It was demonstrated that the IMRT technique can be used not just for small tumors, but also for large and spiral-shaped tumors close to critical organs. The IMRT method requires less planning time, and provides better target coverage with more sparing of critical structures. When planning patients with multiple target volumes receiving different prescribed doses, the IMRT technique can more easily meet this requirement. 2001 American College of Medical Physics.

Purpose: Women with large breasts have marked dose inhomogeneity and often an inferior cosmetic outcome when treated with breast conservation compared to smaller-sized patients. We designed a prone breast board, which both minimizes breast separation and irradiated lung or heart volume. We report feasibility, cosmesis, and preliminary local control and survival for selected women with Stage 0–II breast cancer. Materials and Methods: Fifty-six patients with clinical Stage 0–II breast cancer were treated with lumpectomy and breast irradiation utilizing a prototype prone breast board. A total of 59 breasts were treated. Indications for treatment in the prone position were large or pendulous breast size (n = 57), or a history of cardiopulmonary disease (n = 2). The median bra size was 41D (range, 34D–44EE). Cosmesis was evaluated on a 1–10 (worst-to-best) scale. Results: Acute toxicity included skin erythema (80% of patients experienced Grade I or Grade II erythema), breast edema (72% of patients experienced mild edema), pruritus (20% of patients), and fatigue (20% of patients reported mild fatigue). One patient required a treatment break. The only late toxicity was related to long-term cosmesis. The mean overall cosmesis score for 53 patients was 9.37 (range, 8–10). Actuarial 3- and 5-year local control rates are 98%. Actuarial overall survival at 3 and 5 years are 98% and 94%. Conclusion: Our data indicate that treating selected women with prone breast radiotherapy is feasible and tolerated. The approach results in excellent cosmesis, and short-term outcome is comparable to traditional treatment techniques. This technique offers an innovative alternative to women who might not otherwise be considered candidates for breast conservation.

BACKGROUND Surgical resection and adjuvant radiation therapy are standard therapy for soft tissue sarcomas. When the tumor approximates bone, periosteal excision may be necessary. It was hypothesized that periosteal stripping and radiation therapy would increase the rate of pathologic fracture. METHODS The soft tissue sarcoma data base at the Memorial Sloan-Kettering Cancer Center was used to identify a consecutive series of 205 patients who were treated over a 15-year period (1982-1997). All patients had a soft tissue sarcoma of the thigh, which was managed by limb-sparing surgery and radiation therapy. Patients who had bone invasion by tumor or bone resection were not included. RESULTS Nine patients, including eight women and one man, developed a femoral fracture in an area of previous radiation and surgery. All nine patients had undergone periosteal excision. The risk of fracture, by Kaplan-Meier survivorship, was 29% at 5 years if the resection included periosteum (P < 0.0001). Cox multiple regression analysis showed that periosteal excision was the only independent prognostic factor for the entire set of 205 patients at risk. However, for the subset of 54 patients who had periosteal stripping, two factors were also found to be prognostically important: female gender (P = 0.022) and chemotherapy (P = 0.020). The risk of fracture was 47% and 45%, respectively. The treatment of the fractures was difficult. There were four nonunions and three delayed unions. CONCLUSIONS Periosteal stripping and radiation therapy places the femur at high risk of pathologic fractures, especially for female patients and patients undergoing chemotherapy. When practical, the combination of periosteal stripping and radiation should be avoided. Cancer 1998;82:2356-2365. © 1998 American Cancer Society.

Learning Objectives After completing this course, the reader will be able to: Discuss the incidence of cancer-related fatigue and the impact it has on cancer patients.Evaluate clinical correlates of cancer-related fatigue and describe possible interventions.Explain the time course of cancer-related fatigue before, during, and post-treatment and the effect treatment has on patients for years after treatment. CME This article is available for continuing medical education credit at CME.TheOncologist.com Background. Cancer-related fatigue (CRF) is a highly prevalent and underestimated symptom in cancer patients. This study aims to analyze CRF solely in a cohort of oropharyngeal cancer patients who underwent treatment with radiotherapy (RT). Methods. In January 2008 to June 2010, 87 consecutive oropharyngeal carcinoma patients underwent definitive RT. Concurrent chemotherapy was used for 94% of patients. The median prescription dose to the planning target volume of the gross or clinical tumor volume was 70 Gy for definitive cases (n = 84) and 66 Gy for postoperative cases (n = 3), both delivered over 6.5 weeks. A normalized 12-point numeric rating scale assessed CRF from patient visits before, during, and after RT. Results. The median follow-up of living patients was 14 months. Fatigue peaked 1–2 weeks post-RT and remained higher than baseline for up to 2 years post-RT in 50% of patients. The average fatigue score at the time of completion of therapy or maximum thereafter up to 1 year post-RT was significantly worse than baseline. Patients who experienced pain had a trend toward significance with association for a higher maximum difference in fatigue from baseline. Karnofsky performance status score, weight change, and mood disorders did not correlate with CRF. Conclusions. Fatigue was a common treatment-related symptom in this uniform cohort of patients with oropharyngeal cancer. RT was highly correlated with worsening of CRF. Pain control has the potential to help mitigate CRF in patients experiencing pain, and will need to be confirmed using larger datasets.

Over the past 20 years, it has become evident that limb preservation is possible in the management of soft tissue sarcomas of the extremities. Amputation has been generally replaced by more conservative operations that preserve limb function, followed by radiation therapy. Although external beam irradiation has been the most commonly applied adjuvant, there has been increasing interest in using brachytherapy instead of external beam therapy. The reasons for this tren include the apparent equivalence of local control for properly selected patients using brachytherapy, improved patient convenience, shorter treatment time, and lower cost. A recently published report of a prospective randomized trail shows statistically significant improvement in local control when brachytherapy is added to surgery for high grade sarcomas. The treatment concepts used when using brachytherapy challenge many of the orginal teachings for external beam irradiation with regard to field size, volume irradiated, and the tissues that require treatment in the postoperative setting. This article addresses thse controversies, as well as reviews the evolving role of brachytherapy in the management of soft tissue sarcomas. Issues such as patient selection, integration with other local therapies, and complications are highlighted, and special situations are discussed.

Purpose: To analyze the effect of primary gross tumor volume (pGTV) and nodal gross tumor volume (nGTV) on treatment outcomes in patients treated with definitive intensity-modulated radiation therapy (IMRT) for oropharyngeal cancer (OPC). Methods and Materials: Between September 1998 and April 2009, a total of 442 patients with squamous cell carcinoma of the oropharynx were treated with IMRT with curative intent at our center. Thirty patients treated postoperatively and 2 additional patients who started treatment more than 6 months after diagnosis were excluded. A total of 340 patients with restorable treatment plans were included in this present study. The majority of the patients underwent concurrent platinum-based chemotherapy. The pGTV and nGTV were calculated using the original clinical treatment plans. Cox proportional hazards models and log-rank tests were used to evaluate the correlation between tumor volumes and overall survival (OS), and competing risks analysis tools were used to evaluate the correlation between local failure (LF), regional failure (RF), distant metastatic failure (DMF) vs. tumor volumes with death as a competing risk. Results: Median follow-up among surviving patients was 34 months (range, 5-67). The 2-year cumulative incidence of LF, RF and DF in this cohort of patients was 6.1%, 5.2%, and 12.2%,more » respectively. The 2-year OS rate was 88.6%. Univariate analysis determined pGTV and T-stage correlated with LF (p < 0.0001 and p = 0.004, respectively), whereas nGTV was not associated with RF. On multivariate analysis, pGTV and N-stage were independent risk factors for overall survival (p = 0.0003 and p = 0.0073, respectively) and distant control (p = 0.0008 and p = 0.002, respectively). Conclusions: In this cohort of patients with OPC treated with IMRT, pGTV was found to be associated with overall survival, local failure, and distant metastatic failure.« less

Purpose To update the Memorial Sloan-Kettering Cancer Center's experience with intensity-modulated radiotherapy (IMRT) in the treatment of oropharyngeal cancer (OPC). Methods and Materials Between September 1998 and April 2009, 442 patients with histologically confirmed OPC underwent IMRT at our center. There were 379 men and 63 women with a median age of 57 years (range, 27–91). The disease was Stage I in 2%, Stage II in 4%, Stage III in 21%, and Stage IV in 73% of patients. The primary tumor subsite was tonsil in 50%, base of tongue in 46%, pharyngeal wall in 3%, and soft palate in 2%. The median prescription dose to the planning target volume of the gross tumor was 70 Gy for definitive ( n = 412) cases and 66 Gy for postoperative cases ( n = 30). A total 404 patients (91%) received chemotherapy, including 389 (88%) who received concurrent chemotherapy, the majority of which was platinum-based. Results Median follow-up among surviving patients was 36.8 months (range, 3–135). The 3-year cumulative incidence of local failure, regional failure, and distant metastasis was 5.4%, 5.6%, and 12.5%, respectively. The 3-year OS rate was 84.9%. The incidence of late dysphagia and late xerostomia ≥Grade 2 was 11% and 29%, respectively. Conclusions Our results confirm the feasibility of IMRT in achieving excellent locoregional control and low rates of xerostomia. According to our knowledge, this study is the largest report of patients treated with IMRT for OPC.

To compare concurrent cisplatin (CDDP) and radiation (RT) with cetuximab (C225) and RT for locally advanced head-and-neck cancer (LAHNC).This study retrospectively compared 174 consecutive, newly diagnosed LAHNC patients definitively treated from March 1, 2006, to April 1, 2008, with single-agent CDDP/RT (n = 125) or C225/RT (n = 49). We excluded patients who received additional concurrent, induction, or adjuvant systemic therapy; weekly cisplatin; prior head-and-neck radiotherapy; or primary surgical resection. Outcomes were analyzed by the Kaplan-Meier method, Cox model, and competing-risks analysis tools.The C225/RT patients were older and had decreased creatinine clearance. At a median follow-up of 22.5 months for living patients, the 2-year locoregional failure rate was 5.7% for CDDP/RT and 39.9% for C225/RT (p0.0001). The 2-year failure-free survival (FFS) and overall survival (OS) rates were 87.4% vs. 44.5% (p0.0001) and 92.8% vs. 66.6% (p = 0.0003), respectively, in favor of CDDP/RT. When the Cox proportional hazards model was used for multivariate analysis, treatment with CDDP/RT predicted for improved locoregional control (p0.0001), FFS (p0.0001), and OS (p = 0.01). Late Grade 3 or 4 toxicity or feeding tube dependence 9 months after completion of RT was observed in 21% of patients in the CDDP/RT cohort and 24% in the C225/RT cohort (p = 0.66).In this study of LAHNC patients, CDDP/RT achieved better locoregional control, FFS, and OS than C225/RT. Although the results were upheld on multivariate analysis, they must be interpreted cautiously because of the retrospective nature of the study and significant differences in patient selection. There was no statistically significant difference in late Grade 3 or 4 effects or feeding tube dependence.

Purpose Radiation has been shown to improve local control after resection of soft tissue sarcomas. However, it may also result in major complications in the hand, given the compact nature of functional tissues and limited tissue volumes in the hand. The purpose of this investigation was to describe the hand-specific complications of radiation therapy for patients with soft tissue sarcoma of the hand (STSH). Methods We performed a retrospective chart review of 55 consecutive patients with STSH treated by a single surgeon between 1993 and 2006. We identified 26 patients who were treated with external beam radiation, brachytherapy, or both, either preoperatively or postoperatively, and reviewed their clinical course. Results After a median follow-up of 7 years, 29 treatment-related complications occurred in 19 patients who had received radiation, whereas 3 of the 29 patients treated with surgery alone developed complications. All patients who received brachytherapy and 14 of the 21 treated with external beam radiation alone developed complications. There were 5 early minor, 2 early major, 3 late minor, and 19 late major complications. Conclusions Patients with STSH who underwent radiation therapy had a high rate of complications. The complication rate in our series was higher in patients who had brachytherapy catheters placed adjacent to finger joints. A better understanding of predictors of complications will help to determine the optimal timing and type of radiation therapy to treat patients with STSH. Type of study/level of evidence Therapeutic IV.

The soft-tissue sarcomas (STS) of childhood are a relatively rare and heterogeneous group of tumors that may occur anywhere in the body and respond quite differently to therapy. STSs account for 7.4% of all cancers in children younger than 20 years [1]. These soft tissue sarcomas are divided almost equally between rhabdomyosarcomas originating from striated muscle and nonrhabdomyosarcoma soft tissue sarcomas (NRSTS). Sarcomas are malignant tumors of mesenchymal cell origin. They are named according to the normal tissue they resemble — for example, rhabdomyosarcoma (skeletal muscle), leiomyosarcoma (smooth muscle), and fibrosarcoma and malignant fibrous histiocytoma (connective tissue), neurofibrosarcoma or malignant peripheral nerve sheath tumor (neurofibrosarcomas, as seen in patients with neurofibromatosis), liposarcoma (adipose), synovial sarcoma (synovium), peripheral nerve sheath tumors (peripheral nerve), and angiosarcoma (blood and/or lymphatic vessels). Other sarcomas include rare entities such as alveolar softpart sarcoma, extraosseous Ewing’s sarcoma, peripheral neuroectodermal tumors, epitheloid sarcoma, and hemangiopericytoma.

This study was to investigate the feasibility and potential benefits of combining electrons with intensity modulated photons (IMRT+e) for patients with extensive scalp lesions. A case of a patient with an extensive scalp lesion, in which the target volume covered the entire front half of the scalp, is presented. This approach incorporated the electron dose into the inverse treatment planning optimization. The resulting doses to the planning target volume (PTV) and relevant critical structures were compared. Thermoluminescent dosimeters (TLD), diodes, and GAFCHROMIC EBT films were used to verify the accuracy of the techniques. The IMRT+e plan produced a superior dose distribution to the patient as compared to the IMRT plan in terms of reduction of the dose to the brain with the same dose conformity and homogeneity in the target volumes. This study showed that IMRT+e is a viable treatment modality for extensive scalp lesions patients. It provides a feasible alternative to existing treatment techniques, resulting in improved homogeneity of dose to the PTV compared to conventional electron techniques and a decrease in dose to the brain compared to photon IMRT alone.

Background and purpose To investigate the feasibility and potential benefits of combining electron and photon intensity modulated radiotherapy (IMRT) for patients with malignant pleural mesothelioma (MPM). Patients and methods The planning CT images of 11 MPM patients, six after extrapleural pneumonectomy (EPP) and five after pleurectomy/decortication (P/D), were used for this study. These cases were planned with photon IMRT alone and photon IMRT combined with electrons (IMRT+e). The latter approach incorporated the electron dose into the inverse planning optimization. The resulting doses to the planning target volume (PTV) and relevant critical structures were compared. Results For all patients, the PTV was well covered and doses to critical structures were clinically acceptable for all patients with both techniques. However, IMRT+e exhibited a distinct advantage in reducing the doses to the liver, ipsilateral kidney, contralateral kidney, and heart ( P =0.002, 0.003, 0.025, and 0.001, respectively). Conclusions This study showed that IMRT or IMRT+e is a viable treatment modality for MPM patients. Both plans can provide excellent target coverage and normal tissue sparing, but with the addition of electron beams, the critical structures can be further spared. Additional refining of the electron contribution is expected to further reduce radiation-induced morbidity.

Extraskeletal chondrosarcoma of the leg is a rare, malignant neoplasm with very few cases having been reported in the literature. A case is presented that illustrates the treatment of this malignancy, compares IMRT and conformal radiotherapy techniques, discusses treatment options of the two techniques and their planning time, and assesses the efficacy of using IMRT in other clinical applications. The advantages of IMRT for this difficult clinical application are demonstrated.

Background The purpose of this study was to examine patterns of failure and the relationship to radiation doses in patients with head and neck carcinoma of unknown primary (HNCUP). Methods We reviewed 85 patients with HNCUP treated with curative-intent radiation therapy (RT) during 1995 to 2012. Results There have been no failures in the pharyngeal axis. Relapse at initial neck sites of disease developed in 7 patients (8.2%). The median dose to these sites was 70 Gy (range, 63–70 Gy). Failure at neck sites without initial disease occurred in 4 patients (4.7%). The median dose was 54 Gy (range, 50–58.8 Gy). There were no contralateral failures in a small cohort of patients receiving unilateral treatment (n = 6). Percutaneous endoscopic gastrostomy (PEG) tube dependence at 12 months was 7.4%, and 2.5% at 3 years. Esophageal stricture developed in 5 patients (5.9%). Conclusion RT for HNCUP produces excellent locoregional control rates with acceptably low levels of late toxicity. Doses prescribed to sites of eventual failure did not vary significantly from those sites that were treated and remain in control. © 2015 Wiley Periodicals, Inc. Head Neck 38: E426–E431, 2016

Purpose: It has been a concern that the interplay effect in dynamic radiation treatments of moving targets may compromise dose coverage. In this work we study the interplay-induced dosimetric impact to moving targets in VMAT delivery. Methods: A new patient-specific QA system with ArcCHECK/3DVH v3 (Sun Nuclear Corp) was utilized to estimate “true” dose to a moving target during VMAT delivery. A set of 4DCT scans was acquired for an SBRT lung patient and a VMAT plan was generated using an in-house TPS with ITV (internal-target-volume) generated from the MIPs (maximum-intensity-projections) of 4DCT. The prescribed dose to the PTV (ITV+5mm) was 45Gy in 5 fractions. The motion trajectory was obtained based on the GTVs (gross-tumor-volume) from the 10 phases of 4DCT. The QA system was first used to measure the dose distribution delivered according to the plan. Then, the motion trajectory was incorporated into the QA algorithm to derive the “true” dose coverage, with the virtual motion simulation. Results: The MIP-based ITV had measurable difference from the ITV generated with contoured phases of 4DCT. The dose differences for targets and critical structures between measurements and TPS were: −1.9%, PTV(D95); −3.5%, ITV(D95); 3.0%, max cord; −1%, mean heart; −1.2%, mean esophagus; 1.6%, mean right lung; −0.9%, mean left lung. After accounting for the statistical mean of motion-simulated dose for 5 fractions, the dose differences for the ITV(D95) became −4.1%. However, the dose coverage of the moving GTV itself is nearly unchanged from the plan PTV coverage (

PURPOSE To correlate the pattern of failure and subsequent survival with the technical accuracy of stereotactic brain tumor implantation. METHODS AND MATERIALS The patterns of failure of 47 consecutive patients with primary or recurrent gliomas after stereotactic implantation delivering 60 Gy via removable high activity 125I sources were reviewed. When the tumor was covered at all levels by the chosen isodose distribution, the implant was considered to be "ideal." If the coverage was not complete, a numerical description of the volume of tumor outside the isodose was assigned. Criteria for "adequate" and "inadequate" implants were defined. Standard radiographic criteria, with pathologic confirmation in 26 cases, were used to categorize the patterns of failure into the following components: central, peripheral, distant (within the brain parenchyma), leptomeningeal, and spinal. A peripheral failure was scored as being in the "direction of error" when the prescribed isodose did not cover the tumor volume and the subsequent tumor progression was in this region. Survival was calculated from the date of implantation. RESULTS Of 47 cases examined, 72% had an element of central and/or peripheral failure and 23% had a component of distant or meningeal failure. Among the patients with "adequate" or "inadequate" ("nonideal") implants who had a component of peripheral failure, only 19% were in the "direction of error." All patients with technically "inadequate" implants progressed in both the central and peripheral region. Among the groups who had "ideal," "adequate," and "inadequate" implants; 37%, 70%, and 75%, respectively, underwent reoperation [p = not significant (NS)]. Patients who underwent reoperation had a longer median survival than those who did not; 521 days vs. 298 days, respectively (p = 0.035). For patients with "nonideal" implants, a median survival of 470 days was found for patients undergoing reoperation vs. 184 days for those who did not (p = 0.016). CONCLUSIONS (a) Patients with "inadequate" implants failed in both the central and peripheral region in all cases. This pattern, while less common in those with "ideal" or "adequate" implants, occurred in the majority of cases. (b) The technical excellence of the implant had no impact on survival. (c) Patients with "nonideal" implants were more likely to have reoperation than those with "ideal" implants, and this intervention was associated with a significant survival advantage.

Purpose:Radiotherapy techniques for sparing the hippocampus during cranial irradiation are emerging. This work is to study dose‐painting with volumetric modulated arc therapy (VMAT) in the setting of oligo brain metastases and the clinically relevant dose QA. Methods: A patient having 3 brain metastases was re‐planned using 2‐arc 6 MV photons with in‐house VMAT treatment planning system (TPS). The clinical goal is to dose paint the whole brain and brain metastases to 32 Gy and 63 Gy in 15 fractions, respectively while keeping the mean dose to the hippocampus less than 6 Gy. The VMAT dose QA was carried out using ArcCHECK (AC) and 3DVH (Sun Nuclear Corp) on a Varian Trilogy LINAC. The AC Planned‐Dose‐Perturbation (ACPDP) algorithm was employed to estimate the actual patient dose distribution, at the same grid resolution as that from the TPS calculation. The patient's DICOM RT dose/plan/structures/CT images were loaded into the software. The measured doses and TPS calculated doses for relevant structures were compared. Their differences represented systematic errors induced from the combination of TPS dose calculation algorithm and beam‐delivery. Results: Clinical planning criteria were all satisfied. A 99.5% 3D matching rate for 2%/2mm DD/DTA was observed between the ACPDP reconstruction and TPS‐calculated dose. Despite the excellent agreement, the relative dose differences for patient's critical structures between measurements and TPS are: 0.8%, mean brain lesions; 0.7%, mean whole brain; 9% (

Purpose: To evaluate the measured dose distributions using radiochromic EBT2 films for small fields in iPlan (BrainLab) commissioning. Methods: Radiochromic EBT2 films were irradiated with 6MV photons on a Varian Trilogy linac using polystyrene phantoms. The measurements included dose profiles and depth doses for field sizes of 1×1, 2×2, 3×3, 4×4, and 10×10cm2 etc. The dose profile measurements were taken at the depth of 5cm. The calibration films were irradiated at dmax (1.4cm) for doses up to 6 Gy. Films were scanned using an Epson 10000XL flatbed scanner with 72 dpi resolution. Pixel values were converted to doses using the established calibration‐curve. The 2D dose distributions were generated from the film data analysis. In‐house software was utilized to compare the measured doses from films with the associated treatment planing data. In addition, sample patients' SRS plans were also measured with the EBT2 films for comparison with iPlan. MapCHECK was also used to check the central‐axis doses for the SRS patients' measurements. Results: The measured planar dose distributions achieved more than 95% passing rates with a set of 2%/2mm dose and DTA criteria for all patient treatment fields (< 5×5cm2). Agreement with measurement data with MapCHECK at the central axis (+1%) was found with the plan data. This is the first report for SRS small photon‐field measurements using the latest radiochromic film, EBT2. The results shown in this work indicate that the use EBT2 film provides accurate dosimetry measurements for small photon beams. The measurements show excellent agreement with validated small ion chamber measurements data that were entered into iPlan as commissioning data. Conclusions: The patient‐specific EBT2 film QA for iPlan SRS patients showed good results. The EBT2 films could potentially be a useful dosimeter in verification of commissioning as well as patient‐specific QA for SRS cases.

Purpose: To evaluate current treatment planning system (TPS) dose calculation algorithm for radiation fields with normal and oblique incidence through alpha‐cradle and IGRT couch using radiochromic EBT2 film dosimetry. Methods: A polystyrene phantom (25×25×15cm3) with seven EBT2 films separated by polystyrene slabs, at depths of 0, 1, 2, 5, 10, and 14mm, was positioned above an alpha‐cradle (AC), which was ∼1cm thickness. Such phantom and AC assembly were CT scanned and the CT‐images were transferred to the TPS for calculations in three scenarios: (1) ignoring AC and couch, (2) accounting for AC only, (3) accounting for both AC and IGRT couch. A single PA field and two posterior‐oblique fields (6MV photons, 10×10cm2 from a Varian Trilogy) were planned in the TPS. Each beam was delivered to expose a stack of EBT2 films in the phantom. All films were scanned using an Epson 10000XL flatbed scanner with 72 dpi pixel resolution. The pixel values were converted to doses based on an established calibration curve. Point doses and planar distributions generated from the TPS for the three scenarios were compared with the measurements. Results: The EBT2 film data agree with the doses calculated by our TPS for scenario (3), within the uncertainty of the EBT2 data. The TPS generated doses were lower than the EBT2 doses by 34%, 32%, 31%, 12% for scenario (1) and by 26%, 23%, 22%, 7% for scenario (2) at the depths of 0, 1, 2, and 5mm, respectively. There were no significant differences for the depths of 10 and 14mm. Conclusions: TPS calculation of doses in the buildup region accounting for AC and IGRT couch top was validated by EBT2 film data. Ignoring the presence of AC and/or IGRT couch in TPS calculation would significantly underestimate the doses in the buildup region.