Samir H. Patel

Charged particle therapy versus photon therapy for paranasal sinus and nasal cavity malignant diseases: a systematic review and meta-analysis

BACKGROUND Malignant tumours arising within the nasal cavity and paranasal sinuses are rare and composed of several histological types, rendering controlled clinical trials to establish the best treatment impractical. We undertook a systematic review and meta-analysis to compare the clinical outcomes of patients treated with charged particle therapy with those of individuals receiving photon therapy. METHODS We identified studies of nasal cavity and paranasal sinus tumours through searches of databases including Embase, Medline, Scopus, and the Cochrane Collaboration. We included treatment-naive cohorts (both primary and adjuvant radiation therapy) and those with recurrent disease. Primary outcomes of interest were overall survival, disease-free survival, and locoregional control, at 5 years and at longest follow-up. We used random-effect models to pool outcomes across studies and compared event rates of combined outcomes for charged particle therapy and photon therapy using an interaction test. FINDINGS 43 cohorts from 41 non-comparative observational studies were included. Median follow-up for the charged particle therapy group was 38 months (range 5-73) and for the photon therapy group was 40 months (14-97). Pooled overall survival was significantly higher at 5 years for charged particle therapy than for photon therapy (relative risk 1·51, 95% CI 1·14-1·99; p=0·0038) and at longest follow-up (1·27, 1·01-1·59; p=0·037). At 5 years, disease-free survival was significantly higher for charged particle therapy than for photon therapy (1·93, 1·36-2·75, p=0·0003) but, at longest follow-up, this event rate did not differ between groups (1·51, 1·00-2·30; p=0·052). Locoregional control did not differ between treatment groups at 5 years (1·06, 0·68-1·67; p=0·79) but it was higher for charged particle therapy than for photon therapy at longest follow-up (1·18, 1·01-1·37; p=0·031). A subgroup analysis comparing proton beam therapy with intensity-modulated radiation therapy showed significantly higher disease-free survival at 5 years (relative risk 1·44, 95% CI 1·01-2·05; p=0·045) and locoregional control at longest follow-up (1·26, 1·05-1·51; p=0·011). INTERPRETATION Compared with photon therapy, charged particle therapy could be associated with better outcomes for patients with malignant diseases of the nasal cavity and paranasal sinuses. Prospective studies emphasising collection of patient-reported and functional outcomes are strongly encouraged. FUNDING Mayo Foundation for Medical Education and Research.

Angiosarcoma of the Scalp and Face The Mayo Clinic Experience

IMPORTANCE The etiology and optimal treatment are unknown for angiosarcoma, an aggressive malignant tumor that affects vascular endothelial cells and can be mistaken for benign lesions such as hemangioma. OBJECTIVE To determine the treatment outcomes of patients with angiosarcoma of the face or scalp treated with a combination of surgery, radiation therapy, and/or chemotherapy. DESIGN, SETTING, AND PARTICIPANTS Retrospective study of 55 patients with angiosarcoma of the face or scalp treated between January 1, 1973, and December 31, 2012, at a tertiary-care academic medical institution. INTERVENTIONS Surgery, radiation therapy, and/or chemotherapy. MAIN OUTCOMES AND MEASURES Locoregional control (LRC), recurrence-free survival (RFS), and overall survival (OS). RESULTS Fifty-five patients had angiosarcoma localized to the face or scalp. Forty of these patients (73%) received a combination of surgery, radiation therapy, and/or chemotherapy. Eight patients (15%) were treated with surgery alone, 1 (2%) with radiation alone, 5 (9%) with chemotherapy alone, and 1 (2%) with observation alone. Median (range) follow-up for surviving patients was 25.2 (4.7-227.1) months. Five-year LRC, RFS, and OS (95% CI) were 18% (7%-32%), 16% (6%-31%), and 38% (21%-54%), respectively. Of 36 patients with failed treatment, 34 had failure in a local and/or regional site. On univariate analysis, the use of multimodality therapy (vs no multimodality therapy) was associated with higher 5-year LRC (95% CI) (20% [3%-37%] vs 11% [0%-29%]; P = .04), higher RFS (19% [2%-36%] vs 10% [0%-27%]; P = .02), and higher OS (46% [26%-66%] vs 16% [0%-43%]; P = .04). Age 70 years or older (vs <70 years) was associated with lower 5-year LRC (95% CI) (5% [0%-14%] vs 48% [23%-74%]; P = .02) and lower RFS (5% [0%-13%] vs 49% [24%-75%]; P = .04). Radiation therapy (vs no radiation therapy) was associated with higher 5-year LRC (95% CI) (20% [3%-36%] vs 12% [0%-32%]; P = .02) and higher RFS (19% [2%-35%] vs 12% [0%-31%]; P = .004). On multivariable analysis, age younger than 70 years (vs ≥70 years) was associated with improved 5-year LRC (95% CI) (48% [23%-74%] vs 5% [0%-14%]; P = .03) and RFS (49% [24%-75%] vs 49% [24%-75%]; P = .04). CONCLUSIONS AND RELEVANCE Multimodality therapy for angiosarcoma is associated with improved LRC, RFS, and OS. Younger patients with resectable disease undergoing multimodality therapy for angiosarcoma had the best clinical outcomes.

ACR appropriateness criteria® follow-up and retreatment of brain metastases

Multiple options for retreatment are available, which include whole-brain radiation therapy, stereotactic radiosurgery, surgery, chemotherapy, and supportive care. Size, number, timing, location, histology, performance status, and extracranial disease status all need to be carefully considered when choosing a treatment modality. There are no randomized trials examining the retreatment of brain metastases. Repeat whole-brain radiation has been examined in a single-institution experience, showing the potential for clinical responses in selected patients. Local control rates as high as 91% using stereotactic radiosurgery for relapses after whole-brain radiation are reported. Surgery can be indicated in progressive and/or hemorrhagic lesions causing mass effect. The role of chemotherapy in the recurrent setting is limited but some agents may have activity on the basis of experiences on a smaller scale. Supportive care continues to be an important option, especially in those with a poor prognosis. Follow-up for brain metastases patients is discussed, examining the modality, frequency of imaging, and imaging options in differentiating treatment effect from recurrence. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of the current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

Transoral laser microsurgery followed by radiation therapy for oropharyngeal tumors: The mayo clinic arizona experience

The purpose of this study was to report the treatment outcomes of patients with advanced oropharyngeal cancer treated with transoral laser microsurgery (TLM) followed by radiation therapy (RT) at Mayo Clinic in Arizona.

ACR appropriateness criteria® pre-irradiation evaluation and management of brain metastases

Pretreatment evaluation is performed to determine the number, location, and size of the brain metastases and magnetic resonance imaging (MRI) is the recommended imaging technique, particularly in patients being considered for surgery or stereotactic radiosurgery. A contiguous thin-cut volumetric MRI with gadolinium with newer gadolinium-based agents can improve detection of small brain metastases. A systemic workup and medical evaluation are important, given that subsequent treatment for the brain metastases will also depend on the extent of the extracranial disease and on the age and performance status of the patient. Patients with hydrocephalus or impending brain herniation should be started on high doses of corticosteroids and evaluated for possible neurosurgical intervention. Patients with moderate symptoms should receive approximately 4-8 mg/d of dexamethasone in divided doses. The routine use of corticosteroids in patients without neurologic symptoms is not necessary. There is no proven benefit of anticonvulsants in patient without seizures. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

Prognostic impact of atrial fibrillation on clinical outcomes of acute coronary syndromes, heart failure and chronic kidney disease

Atrial fibrillation (AF) is the most common type of sustained arrhythmia, which is now on course to reach epidemic proportions in the elderly population. AF is a commonly encountered comorbidity in patients with cardiac and major non-cardiac diseases. Morbidity and mortality associated with AF makes it a major healthcare burden. The objective of our article is to determine the prognostic impact of AF on acute coronary syndromes, heart failure and chronic kidney disease. Multiple studies have been conducted to determine if AF has an independent role in the overall mortality of such patients. Our review suggests that AF has an independent adverse prognostic impact on the clinical outcomes of acute coronary syndromes, heart failure and chronic kidney disease.

Relapse patterns after transoral laser microsurgery and postoperative irradiation for squamous cell carcinomas of the tonsil and tongue base.

Objectives: We evaluated relapse patterns after transoral laser microsurgery (TLM) in squamous cell carcinoma (SCC) of the tonsil and tongue base and evaluated the indications for adjuvant irradiation. Methods: Between December 1, 1996, and December 31, 2005, 79 patients with previously untreated SCC of the tonsil or tongue base underwent TLM with or without neck dissection. Thirty-eight patients (48%) underwent postoperative irradiation (median, 62 Gy) to the primary site and the neck. Analysis of relapse patterns was performed on the basis of adverse risk factors and the presence or absence of adjuvant irradiation. Results: The median follow-up for living patients was 47 months (range, 10 to 107 months), and patients were monitored for at least 2 years or until recurrence or death. Local, regional, and distant treatment failures numbered 4, 6, and 4 for surgery alone (n = 41) and 0, 2, and 6 for adjuvant irradiation (n = 38), respectively. Patients with high-risk features (extracapsular extension or at least 2 adverse factors) had locoregional control rates at 2 or more years of 66% and 94% for TLM alone and TLM plus adjuvant irradiation, respectively. Conclusions: Adjuvant irradiation after TLM resection of oropharyngeal SCC with intermediate- or high-risk features improves locoregional control compared with TLM alone.

High-grade neuroendocrine carcinoma of the larynx: The mayo clinic experience

Objective: To report a single institutional series of high-grade neuroendocrine carcinoma of the larynx (NCL), a very rare yet aggressive tumor. To review the management of NCL, including discussion of clinical behavior, treatment outcome, and prognosis. Method: A retrospective chart review of high-grade laryngeal neuroendocrine carcinomas at a single institution, including small- and large-cell neuroendocrine carcinomas. A total of 8 patients with high-grade NCL treated at our institution from 1992 to 2014 were identified. Results: The median age at diagnosis was 65.5 years (range, 43-80). Five patients were male. Two patients had a known smoking history. Primary tumor location was supraglottic in 7 patients and glottic in 1 patient. Primary treatment consisted of surgery alone (3 patients), radiotherapy alone (1 patient), combination of chemotherapy and radiotherapy (1 patient), and surgery followed by postoperative chemoradiotherapy (3 patients). Locoregional recurrence followed by distant metastasis occurred in 6 patients. Median overall survival was 44.0 months (95% CI, 3-62.0). Conclusion: High-grade NCL is a rare diagnosis. Compared to well- and moderately differentiated NCL, high-grade NCL has a far more aggressive clinical course and associated with a worse prognosis. To our knowledge, this is the largest series of patients with high-grade NCL treated at a single institution. Prompt diagnosis and multimodality therapy including elective neck dissection may improve survival.

Endoscopic resection of sinonasal mucosal melanoma has comparable outcomes to open approaches

Background Endoscopic endonasal resection (EER) of sinonasal mucosal melanoma (SMM) is a newer surgical alternative to traditional external and/or open resection (OR). Studies on long-term outcomes are necessary to validate EER for this aggressive sinonasal malignancy. Objective To compare outcomes of EER versus OR in SMM. Methods A case series of patients who underwent surgical resection of SMM at a tertiary-care institution (2000–2015) was studied retrospectively. Demographics, tumor site and stage, surgical approach, surgical margin status, local control, and survival were compared between those who underwent EER and OR. Results Twenty-two patients met inclusion criteria. Nine underwent EER and 13 underwent OR. The mean age in the EER and OR groups was similar, 78.7 and 72.3 years, respectively. Two-thirds of patients were women (EER, 66.7%; OR, 61.5%). The nasal cavity was the most common primary tumor site (EER, 77.8%; OR, 84.6%). The local tumor stage in both groups was similar, with the majority of cases being T4 (EER, 55.6%; OR, 61.5%; p = 0.99). Negative margins were achieved in all EERs and in 69.2% of ORs. Median follow-up was 25.0 months for the overall group (range, 1.7–172.9 months), 32.6 months (range, 3.4–58.7 months) for EER and 14.1 months (range, 1.7–172.9 months) for OR cohorts. The 5-year overall survival was statistically similar in both groups (EER, 53.3%; OR, 22.7%; p = 0.214) as was disease-free survival (EER, 55.6%; OR, 22.8%; p = 0.178). Local control, however, was significantly higher in the EER cohort (EER, 85.7%; OR, 37.6%; p = 0.026). Conclusion In carefully selected patients with sinonasal melanoma, endoscopic surgery with an experienced team may offer comparable survival and improved local control over open surgery. Prospective, multicentered studies with larger cohorts are needed to validate these results.

Robust intensity-modulated proton therapy to reduce high linear energy transfer in organs at risk.

Purpose: We propose a robust treatment planning model that simultaneously considers proton range and patient setup uncertainties and reduces high linear energy transfer (LET) exposure in organs at risk (OARs) to minimize the relative biological effectiveness (RBE) dose in OARs for intensity‐modulated proton therapy (IMPT). Our method could potentially reduce the unwanted damage to OARs. Methods: We retrospectively generated plans for 10 patients including two prostate, four head and neck, and four lung cancer patients. The “worst‐case robust optimization” model was applied. One additional term as a “biological surrogate (BS)” of OARs due to the high LET‐related biological effects was added in the objective function. The biological surrogate was defined as the sum of the physical dose and extra biological effects caused by the dose‐averaged LET. We generated nine uncertainty scenarios that considered proton range and patient setup uncertainty. Corresponding to each uncertainty scenario, LET was obtained by a fast LET calculation method developed in‐house and based on Monte Carlo simulations. In each optimization iteration, the model used the worst‐case BS among all scenarios and then penalized overly high BS to organs. The model was solved by an efficient algorithm (limited‐memory Broyden–Fletcher–Goldfarb–Shanno) in a parallel computing environment. Our new model was benchmarked with the conventional robust planning model without considering BS. Dose–volume histograms (DVHs) of the dose assuming a fixed RBE of 1.1 and BS for tumor and organs under nominal and uncertainty scenarios were compared to assess the plan quality between the two methods. Results: For the 10 cases, our model outperformed the conventional robust model in avoidance of high LET in OARs. At the same time, our method could achieve dose distributions and plan robustness of tumors assuming a fixed RBE of 1.1 almost the same as those of the conventional robust model. Conclusions: Explicitly considering LET in IMPT robust treatment planning can reduce the high LET to OARs and minimize the possible toxicity of high RBE dose to OARs without sacrificing plan quality. We believe this will allow one to design and deliver safer proton therapy.