Yttrium-90 Internal Radiation Therapy as Part of the Multimodality Treatment of Metastatic Colorectal Carcinoma

About 70% of patients with metastatic colorectal carcinoma (mCRC) have liver metastases. Hepatic failure accounts for most mCRC-related deaths. Therefore, controlling liver metastases may improve outcomes. A data overview of liver-directed treatment using yttrium-90 selective internal radiation therapy (SIRT) is provided as part of a multimodality treatment. SIRT in mCRC is discussed, and the prognostic factors for patient selection are defined. Pooled analyses of three recent trials incorporating SIRT plus chemotherapy revealed subsets of patients with mCRC who might benefit from SIRT. A multidisciplinary treatment for most mCRC patients is proposed to achieve long-term survival in this cohort of patients.

Esthesioneuroblastoma with recurrent dural metastases: Long-term multimodality treatment and considerations

Background: Esthesioneuroblastoma (ENB) is a rare malignant disease and treatment protocols have not been standardized, varying widely by disease course and institutional practices. Management typically includes wide local excision through open or endoscopic resection, followed by radiotherapy, chemotherapy, and stereotactic radiosurgery. Tumor control can differ on a case-by-case basis. Herein, the complex management of a rare case of recurrent disease with multiple dural metastases is presented. Case Description: A 60-year-old patient was diagnosed with ENB after presenting with anosmia and epistaxis. The patient underwent combined endonasal and transfrontal sinus craniofacial resection, followed by proton beam radiation therapy and chemotherapy. Subsequently, he developed a total of 25 dural metastases that were controlled with repeated Gamma Knife Radiosurgery (GKRS). In spite of post-treatment course that was complicated by radiation necrosis and local vasculopathy, the patient made significant recovery to functional baseline. Conclusion: The management of ENB entails multimodality and multidisciplinary care, which can help patients obtain disease control and long-term survival. Recurrent ENB dural metastases can behave as oligometastatic disease manageable with aggressive focal GKRS. As prognosis continues to improve, chronic treatment effects of radiation in such cases should be taken into consideration.

SMARCA4/BRG1-Deficient Sinonasal Carcinoma: Morphologic Spectrum of an Evolving Entity

Context.— Molecular analysis of poorly differentiated/undifferentiated sinonasal neoplasms has resulted in identification of a growing number of genetically defined tumors. SMARCA4-deficient sinonasal carcinoma is one such recently described entity that emerged from within sinonasal undifferentiated carcinoma (SNUC), neuroendocrine carcinoma (NEC), and teratocarcinosarcoma (TCS). Objective.— To identify SMARCA4-deficient sinonasal carcinomas from a large institutional cohort of poorly differentiated/undifferentiated carcinomas and evaluate their clinicopathologic features. Design.— SMARCA4/BRG1 immunohistochemistry was performed on all tumors diagnosed as SNUC, poorly differentiated carcinoma, NEC, and TCS during a 12-year period. SMARCA2/BRM and INSM1 immunostaining was performed in SMARCA4-deficient cases. Results.— Twelve SMARCA4-deficient sinonasal carcinomas were identified among 299 cases. Morphologically, 5 cases were large cell NEC, 2 cases were small cell NEC, and 5 were TCS. SMARCA4 loss was diffuse and complete in 10 cases, while 2 cases showed focal retention. Most cases showed diffuse cytokeratin staining accompanied by weak, usually focal staining for chromogranin and synaptophysin. INSM-1 showed negativity in most cases. All cases showed retained SMARCA2 expression. IDH1/2 mutation was absent in all cases analyzed. Four of 7 patients died of disease, and aggressive multimodality treatment had better outcome. Conclusions.— SMARCA4-deficient sinonasal carcinomas are morphologically akin to sinonasal poorly differentiated NECs and TCS, display cytokeratin positivity and only focal staining for neuroendocrine markers, and have aggressive biological behavior. Inclusion of SMARCA4 in the immunohistochemical panel for diagnostic workup of all sinonasal NEC and TCS phenotypes will facilitate their early recognition. Comprehensive germline and somatic mutational analyses of these tumors are necessary for further insights into their molecular pathogenesis.

Multimodality Management of EBV-Associated Nasopharyngeal Carcinoma

Nasopharyngeal carcinoma (NPC) is a rare cancer of the nasopharyngeal mucosa with a specific geographic predisposition. NPC is often associated with Epstein–Barr Virus (EBV) infection and as a result contains many characteristic biomarkers. Treatment of locally-contained NPC is generally achieved through use of radiotherapy (RT), as part of a multimodality treatment regimen. Induction chemotherapy followed by concurrent RT and platinum-based chemotherapy regimen has emerged as the definitive treatment of choice for locoregionally-advanced NPC. Recently, immunotherapy is finding a role in the treatment of recurrent or metastatic NPC. Immune checkpoint blockade therapies targeted against the programmed death-1 (PD-1) receptor have demonstrated efficacy in early phase clinical trials, with ongoing phase III trials in effect. Biomarkers for treatment efficacy remain an ongoing area of investigation, with important prognostic implications on the horizon.

Relationship between Treatment Plan Dosimetry, Toxicity, and Survival following Intensity-Modulated Radiotherapy, with or without Chemotherapy, for Stage III Inoperable Non-Small Cell Lung Cancer

Concurrent chemoradiotherapy (cCRT) is the preferred treatment for stage III NSCLC because surgery containing multimodality treatment is often not appropriate. Alternatives, often for less fit patients, include sequential CRT and RT alone. Many reports describing the relationship between overall survival (OS), toxicity, and dosimetry are based on clinical trials, with strict criteria for patient selection. We performed an institutional analysis to study the relationship between dosimetric parameters, toxicity, and OS in inoperable patients with stage III NSCLC treated with (hybrid) IMRT/VMAT-based techniques in routine clinical practice. Eligible patients had undergone treatment with radical intent using cCRT, sCRT, or RT alone, planned to a total dose ≥ 50 Gy delivered in ≥15 fractions. All analyses were performed for two patient groups, (1) cCRT (n = 64) and (2) sCRT/RT (n = 65). The toxicity rate differences between the two groups were not significant, and OS was 29 and 17 months, respectively. For sCRT/RT, no dosimetric factors were associated with OS, whereas for cCRT, PTV-volume, esophagus V50 Gy, and contralateral lung V5 Gy were associated. cCRT OS was significantly lower in patients with esophagitis ≥ G2. The overall rate of ≥G3 pneumonitis was low (3%), and the rate of high-grade esophagitis the OS in this real-world patient population was comparable to those reported in clinical trials. Based on this hypothesis-generating data, more aggressive esophageal sparing merits consideration. Institutional auditing and benchmarking of the planning strategy, dosimetry, and outcome have an important role to play in the continuous quality improvement process.

Multimodality Treatment in Metastatic Gastric Cancer: Working Together to Tailor the Continuum of Care

Gastric cancer (GC) represents one of the most frequent and lethal tumors worldwide today, finding itself in fifth place in terms of incidence and third in terms of mortality [...]

The Use of Intraoperative Radiation Therapy (IORT) in Multimodality Management of Cancer Patients. A Single Institution Experience.

Background Intraoperative radiation therapy (IORT) is a highly conformal technique given in the operating room in many cancer sites for better tumor local control by increasing the tumor radiation dose without exceeding normal tissues tolerance doses.Purpose Assess the feasibility of Intra operative radiation therapy (IORT) and short-term toxicity in patients with different cancer sites treated with a multidisciplinary protocols including IORT.Patients & MethodsMedical records of cancer patients who received IORT at King Faisal Specialized Hospital and Research center(KFSHRC), Riyadh, Saudi Arabia from 2013 until 2017 were retrospectively reviewed.ResultsTotal 188 patients with 212 IORT applications were analyzed. Twenty-four patients had more than one application.116 patients were males. Median age at time of diagnosis was 49.5years (19-77). Hundred thirty four patients had primary while 54 cases had recurrent disease. Gastro esophageal cancer and soft tissue sarcoma were the most frequent diagnosis in 49 patients followed by colorectal cancer in 35 patients. Major surgeries with curative intent done in 183 patients (97.3%) and 118 patients (62.8%) had hyperthermic intraperitoneal chemotherapy (HIPEC) in addition to IORT. The 30days postoperative mortality rate was 3.2%. Fifty-three (28.2%) patients develop Grade III-IV complications according to Clavien-Dindo grading system. ConclusionThe data presented discussing treatment modalities for different malignant tumors which are treated and may benefit from using IORT technique as a part of multimodality treatment. IORT seems safe and feasible, however a longer follow-up is needed for proper evaluation and defining the role of IORT in tailored multimodality approach.

Downstaging Conversion Therapy in Patients With Initially Unresectable Advanced Hepatocellular Carcinoma: An Overview

The high mortality rate associated with hepatocellular carcinoma (HCC) is partly due to the high proportion of patients who present with advanced stage disease at diagnosis, for whom there are limited treatment options. For selected patients with initially unresectable HCC, locoregional and/or systemic treatments can result in tumor downstaging and consequently provide opportunities for surgical intervention and the potential for long-term survival. Therefore, the key aim of ‘conversion therapy’ is to reduce tumor burden so that patients become amenable to surgical resection. Various therapies have been investigated as candidates for downstaging patients with potentially resectable HCC including transarterial chemoembolization, transarterial radioembolization with yttrium-90 microspheres, radiotherapy, systemic therapies and combination or multimodality treatment approaches. However, downstaging conversion therapy remains controversial and there are several challenges such as defining the criteria used to identify the population of patients who are ‘potentially resectable’, the criteria used to define successful downstaging, and the optimum treatment approach to maximize the success of downstaging therapy. In this review article, we summarize clinical experience and evidence of downstaging conversion treatment in patients identified as having ‘potentially resectable’ HCC.

When Everything Revolves Around Internal Carotid Artery: Analysis of Different Management Strategies in Patients With Very Advanced Cancer Involving the Skull Base

Internal or common carotid artery encasement (CAE) is observed in almost 2-7% of head and neck cancers (HNC) and designates the tumor with the T4b category. This clinical scenario is associated with a dismal prognosis, owing to the risk for thrombosis and bleeding that usually characterizes such an advanced cancer. Standardized radiological criteria to infer invasion of the carotid artery are lacking. Complete surgical resection in the context of a multimodality treatment is supposed to offer the greatest chances of cure. Surgery can either be carotid-sparing or include carotidectomy. Data on probability of cerebrovascular and non-cerebrovascular complications, risk of carotid blowout, poor oncologic outcomes, and less-than-certain efficacy of diagnostic and interventional preventive procedures against cerebral infarction make it difficult to define surgery as the recommended option among other therapeutic strategies. Non-surgical therapies based on radiation therapy possibly combined with chemotherapy are more frequently employed in HNC with CAE. In this context, carotid blowout is the most feared complication, and its probability increases with tumor stage and cumulative radiation dose received by the vessel. The use of highly conformal radiotherapies such as intensity-modulated particle therapy might substantially improve the manageability of HNC with CAE by possibly reducing the risk of late sequalae. Despite evidence is frail, it appears logical that a case-by-case evaluation through multidisciplinary decision making between head and neck surgeons, radiation oncologists, medical oncologists, diagnostic and interventional radiologists, and vascular surgeons are of paramount value to offer the best therapeutic solution to patients affected by HNC with CAE.