Roi Dagan

The significance of a marginal excision after preoperative radiation therapy for soft tissue sarcoma of the extremity

Marginal excision of soft tissue sarcoma (STS), defined as resection through the tumor pseudocapsule or surrounding reactive tissue, increases the likelihood of local recurrence and necessitates re‐excision or postoperative radiation. However, its impact after preoperative radiation therapy (RT) remains unclear. This study therefore investigated the significance of marginal margins in patients treated with preoperative RT for extremity STS, reporting long‐term local control and limb preservation endpoints.

Elective neck dissection during salvage surgery for locally recurrent head and neck squamous cell carcinoma after radiotherapy with elective nodal irradiation.

To define the role of elective neck dissection during salvage surgery for locally recurrent head and neck squamous cell carcinoma (SCCA) initially treated with elective nodal irradiation (ENI).

Long-term Results following Postoperative Radiotherapy for Soft Tissue Sarcomas of the Extremity

PURPOSE To review long-term outcomes following postoperative radiotherapy (RT) for extremity soft tissue sarcoma (STS) and identify variables affecting the therapeutic ratio. METHODS AND MATERIALS Between 1970 and 2008, 173 patients with localized extremity STS were treated with postoperative radiation. No patients received prior irradiation. Sixteen percent of tumors had recurred after initial surgery alone; 89% of tumors were high grade. The median patient age was 57 years (range, 18-86 years). Sixty-one percent underwent >1 surgery before RT in an attempt to achieve wide negative margins. Final margin status was negative in 70% and marginal or microscopically positive in 30%. The median time between final surgery and start of RT was 40 days. The median RT dose was 65 Gy (range, 49-74 Gy). The median follow-up for all patients was 10.4 years and 13.2 years among survivors. RESULTS At 10 years, local control (LC), cause-specific survival (CSS), and overall survival (OS) rates were 87%, 80%, and 70%, respectively, with 89% of local failures occurring within 3 years after treatment. On multivariate analysis, age >55 years (82% vs 93%, P<.05) and recurrent presentation (67% vs 91%, P<.05) were associated with inferior 10-year LC. The LC according to final margin status was 90% for wide negative margins vs 79% for marginal/microscopically positive margins (P=.08). Age>55 years and local recurrence were associated with inferior CSS and OS on multivariate analysis. Twelve percent of patients experienced grade 3+ toxicity; 12 of these occurred in patients with tumors of the proximal lower extremity, with the most common toxicity of pathologic fracture occurring in 6.3%. CONCLUSIONS This large single-institution series confirms that postoperative RT for STS of the extremities provides good long-term disease control with acceptable toxicity. Our experience supports recurrent presentation and older age as adverse prognostic factors for LC.

Initial Report of a Prospective Dosimetric and Clinical Feasibility Trial Demonstrates the Potential of Protons to Increase the Therapeutic Ratio in Breast Cancer Compared With Photons.

PURPOSE To compare dosimetric endpoints between proton therapy (PT) and conventional radiation and determine the feasibility of PT for regional nodal irradiation (RNI) in women with breast cancer. METHODS AND MATERIALS From 2012 to 2014, 18 women (stage IIA-IIIB) requiring RNI prospectively enrolled on a pilot study. Median age was 51.8 years (range, 42-73 years). The cohort included breast-conserving therapy (BCT) and mastectomy patients and right- and left-sided cancers. Treatment targets and organs at risk were delineated on computed tomography scans, and PT and conventional plans were developed. Toxicity was prospectively recorded using Common Terminology Criteria for Adverse Events version 4.0. A Wilcoxon signed-rank sum test compared the dose-volume parameters. The primary endpoint was a reduction in cardiac V5. RESULTS Median follow-up was 20 months (range, 2-31 months). For all patients, the PT plan better met the dosimetric goals and was used for treatment. Proton therapy alone was used for 10 patients (9 postmastectomy, 1 after BCT) and combined proton-photon in 8 (6 BCT, 2 postmastectomy with immediate expander reconstruction). Proton therapy improved coverage of level 2 axilla (P=.0005). Adequate coverage of internal mammary nodes was consistently achieved with PT (median D95, 50.3 Gy; range, 46.6-52.1 Gy) but not with conventional radiation therapy (median D95, 48.2 Gy; range, 40.8-55 Gy; P=.0005). Median cardiac V5 was 0.6% with PT and 16.3% with conventional radiation (P<.0001). Median ipsilateral lung V5 and V20 were improved with PT (median V5 35.3% vs 60.5% [P<.0001]; and median V20, 21.6% vs 35.5% [P<.0001]). Grade 3 dermatitis developed in 4 patients (22%), which was the only grade 3 toxicity. No grade 4+ toxicities developed. CONCLUSION Proton therapy for RNI after mastectomy or BCT significantly improves cardiac dose, especially for left-sided patients, and lung V5 and V20 in all patients without excessive acute toxicity. Proton therapy simultaneously improves target coverage for the internal mammary nodes and level 2 axilla, which may positively impact long-term survival in breast cancer patients.

Prognostic significance of paraglottic space invasion in T2N0 glottic carcinoma

Purpose:The purpose of this study was to evaluate the prognostic significance of paraglottic space invasion determined with pretreatment computed tomography (CT) for patients with T2N0 glottic carcinoma treated with radiotherapy (RT). Methods:Eighty patients with T2N0 glottic squamous cell carcinomas treated with definitive RT between 1983 and 2002 who had pretreatment CT information available regarding paraglottic space invasion were analyzed. Follow up ranged from 0.14 to 18 years (median, 7.1 years). No patient was lost to follow up. Results:Five-year outcomes were: local control, 78%; local control with larynx preservation, 80%; relapse-free survival, 71%; and cause-specific survival, 91%. Multivariate analyses of various parameters (including vocal cord mobility, paraglottic space invasion, supraglottic invasion, and subglottic extension) showed that only subglottic extension significantly influenced the probability of cure. Conclusion:Paraglottic space invasion is likely associated with increased tumor volume and, by itself, is not necessarily associated with poorer outcome after definitive RT.

Combination therapy for renal cell cancer: what are possible options?

Antiangiogenic therapy has shown promise in the treatment of patients with renal cell carcinoma (RCC). Two classes of antiangiogenic drugs, the anti-vascular endothelial growth factor antibody bevacizumab and the tyrosine kinase inhibitors sorafenib, sunitinib and pazopanib, have shown efficacy in patients with RCC and are approved by the US Food and Drug Administration for treatment of this cancer. In practice, the clinical benefit of antiangiogenic drugs in RCC has been heterogeneous, and in patients who do respond, benefits are modest and/or short-lived. To improve efficacy, combination targeted therapy has been attempted, but with either very limited additional efficacy or nontolerable toxicities. Recent advances in the molecular understanding of tumor angiogenesis and mechanism of resistance, along with the rapid development of targeted drug discovery, have made it possible to further explore novel combination therapy for RCC.

Outcomes of Sinonasal Cancer Treated With Proton Therapy

PURPOSE To report disease outcomes after proton therapy (PT) for sinonasal cancer. METHODS AND MATERIALS Eighty-four adult patients without metastases received primary (13%) or adjuvant (87%) PT for sinonasal cancers (excluding melanoma, sarcoma, and lymphoma). Common histologies were olfactory neuroblastoma (23%), squamous cell carcinoma (22%), and adenoid cystic carcinoma (17%). Advanced stage (T3 in 25% and T4 in 69%) and high-grade histology (51%) were common. Surgical procedures included endoscopic resection alone (45%), endoscopic resection with craniotomy (12%), or open resection (30%). Gross residual disease was present in 26% of patients. Most patients received hyperfractionated PT (1.2 Gy [relative biological effectiveness (RBE)] twice daily, 99%) and chemotherapy (75%). The median PT dose was 73.8 Gy (RBE), with 85% of patients receiving more than 70 Gy (RBE). Prognostic factors were analyzed using Kaplan-Meier analysis and proportional hazards regression for multiple regression. Dosimetric parameters were evaluated using logistic regression. Serious, late grade 3 or higher toxicity was reported using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4. The median follow-up was 2.4 years for all patients and 2.7 years among living patients. RESULTS The local control (LC), neck control, freedom from distant metastasis, disease-free survival, cause-specific survival, and overall survival rates were 83%, 94%, 73%, 63%, 70%, and 68%, respectively, at 3 years. Gross total resection and PT resulted in a 90% 3-year LC rate. The 3-year LC rate was 61% for primary radiation therapy and 59% for patients with gross disease. Gross disease was the only significant factor for LC on multivariate analysis, whereas grade and continuous LC were prognostic for overall survival. Six of 12 local recurrences were marginal. Dural dissemination represented 26% of distant recurrences. Late toxicity occurred in 24% of patients (with grade 3 or higher unilateral vision loss in 2%). CONCLUSIONS Dose-intensified, hyperfractionated PT with or without concurrent chemotherapy results in excellent LC after gross total resection, and results in patients with gross disease are encouraging. Patients with high-grade histology are at greater risk of death from distant dissemination. Continuous LC is a major determinant of survival justifying aggressive local therapy in nearly all cases.

Toxicological Approach for Assessing the Heavy Metal Binding Capacity of Soils

A toxicological approach was taken to determine the heavy metal binding capacity of soils. A soil heavy metal binding capacity (SHMBC) methodology was developed and was based on the use of the MetPLATE TM toxicity test kit, a bioassay that is specific for heavy metal toxicity. SHMBC test is based on the heavy metal binding capacity (HMBC) concept that has been considered in the assessment of the metal binding capacity of surface waters (Huang et al., 1999) and solid wastes landfill leachates (Ward et al., 2005). SHMBC is the ratio of the EC 50 of an added metal in a soil sample divided by the EC 50 of a metal in a reference soil (clean Ottawa sand). A higher SHMBC value indicates higher metal binding to soil and lower bioavailability and potential toxicity to the test bacteria. Five soils (two sandy soils, two organic soils and a clay soil) were used to determine their binding capacity towards Cu, Zn, and Hg, using the developed SHMBC test. The test measured the ability of the solids to reduce metal bioavailability and toxicity. SHMBC was highest for the clay soil and lowest for the sandy soils. The potential application of this relatively rapid (a few hours) test to predict metal toxicity to terrestrial plants is discussed.

Response to sunitinib in combination with proton beam radiation in a patient with chondrosarcoma: a case report

IntroductionChondrosarcoma is well-known to be primarily resistant to conventional radiation and chemotherapy.Case presentationWe present the case of a 32-year-old Caucasian man with clear cell chondrosarcoma who presented with symptomatic recurrence in his pelvis and metastases to his skull and lungs. Our patient underwent systemic therapy with sunitinib and then consolidation with proton beam radiation to his symptomatic site. He achieved complete symptomatic relief with a significantly improved performance status and had an almost complete and durable metabolic response on fluorine-18-fluorodeoxyglucose positron emission tomography.ConclusionsOur findings have important clinical implications and suggest novel clinical trials for this difficult to treat disease.

A multi-national report on stereotactic body radiotherapy for oligometastases: Patient selection and follow-up*

Abstract Aims Stereotactic body radiotherapy (SBRT) for oligometastases is increasingly used with few evidenced-based guidelines. We conducted a survey to determine patient selection and follow-up practice patterns. Materials and methods Seven institutions from US, Canada, Europe, and Australia that recommend SBRT for oligometastases participated in a 72-item survey. Levels of agreement were categorized as strong (6–7 common responses), moderate (4–5), low (2–3), or no agreement. Results There was strong agreement for recommending SBRT for eradication of all detectable oligometastases with most members limiting the number of metastases to five (range 2–5) and three within a single organ (range 2–5). There was moderate agreement for recommending SBRT as consolidative therapy after systemic therapy. There was strong agreement for requiring adequate performance status and no concurrent chemotherapy. Additional areas of strong agreement included staging evaluations, primary diagnosis, target sites, and follow-up recommendations. Several differences emerged, including the use of SBRT for sarcoma oligometastases, treatment response evaluation, and which imaging should be performed during follow-up. Conclusion Significant commonalities and variations exist for patient selection and follow-up recommendations for SBRT for oligometastases. Information from this survey may serve to help clarify the current landscape.