Colorectal cancer is one of the major leading causes of death in both men and women. The successful management of colon or rectal cancer demands a multidisciplinary approach. In the last few years, significant improvement has been noticed in the management of localized rectal cancer to reduce local recurrence and obtain complete pathological response following appropriate surgical steps, if necessary. Implementation of neoadjuvant therapy not only enhances disease control, it may also ensure sphincter preserving procedures or organ-preserving options. This article principally concentrates on the current neoadjuvant treatment for locally advanced rectal cancer and the prognostic outcomes of such therapy, including a discussion on the historical perspective.

Purpose-Few studies to date have evaluated factors associated with the development of radiation pneumonitis (RP) in patients with Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL), especially in patients treated with contemporary radiation techniques. These patients represent a unique group owing to the often large radiation target volumes within the mediastinum and to the potential to receive several lines of chemotherapy that add to pulmonary toxicity for relapsed or refractory disease. Our objective was to determine the incidence and clinical and dosimetric risk factors associated with RP in lymphoma patients treated with intensity modulated radiation therapy (IMRT) at a single institution. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Methods-We Conflicts of Interest: None HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript acute toxicity criteria were identified in univariate analysis using the Pearson χ 2 test and logistic multivariate regression.Results-Mediastinal radiation was administered as consolidation therapy in 110 patients with newly diagnosed HL or NHL and in 40 patients with relapsed or refractory disease. The overall incidence of RP (RTOG grade 1-3) was 14% in the entire cohort. Risk of RP was increased for patients who received radiation for relapsed or refractory disease (25%) versus those who received consolidation (10%, P=0.019). Several dosimetric parameters predicted RP, including mean lung dose (MLD) >13.5 Gy, V 20 >30%, V15 >35%, V 10 >40% and V 5 >55%. The likelihood ratio (LR) χ 2 value was highest for V 5 < 55% (LR χ 2 =19.37).Conclusions-In using IMRT to treat mediastinal lymphoma, all dosimetric parameters predicted RP, although small doses to large volumes of lung had the greatest influence. Patients with relapsed or refractory lymphoma who received salvage chemotherapy and hematopoietic stem cell transplantation were at higher risk for symptomatic RP.

Rectal cancer has been successfully managed in the last couple of decades. In the USA, as the initial approach, neoadjuvant concurrent chemoradiation has been associated not only with decrease in tumor size and recurrence but also with higher resection rate with minimal side effects. Data support that addition of chemotherapy to radiotherapy is superior to radiotherapy alone in the neoadjuvant setting. Recent debates have addressed the question of administration of adjuvant chemotherapy following surgery. In this article, we discuss the role of chemotherapy in both the neoadjuvant and the adjuvant settings for locally advanced rectal cancer.

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298 Background: Appendiceal adenocarcinomas (AAs) are orphan tumors. Little is known about their molecular profile limiting understanding of their biology and development of novel targeted therapies. The purpose of this study was to delineate the molecular landscape of AAs. Methods: We performed a retrospective review of AAs patients (pts) who were evaluated at MD Anderson Cancer Center between October 2012 and April 2017 and underwent next-generation sequencing (NGS) with internal or external assays (at least 45 genes) using either tumor tissue specimens or peripheral blood for circulating cell-free DNA (cfDNA). The primary outcome was to assess the prevalence of genomic alterations (GAs) in AAs. We then performed comparative exploratory analyses of GAs using TCGA colorectal cancer (CRC) sequencing. Results: A total of 78 patients were identified of which 57 (73%) and 18 (23%) underwent tissue based and ctDNA based sequencing, respectively (3 cases had both). At least 1 GA was found in 61 (78%) of AA specimens, with a mean (SD) of 2.8 (1.6) GAs per case. Of these 44 (72%) had ≥ 2 GAs and 31 (51%) had ≥ 3 GAs. The most frequent GAs were KRAS (38 [62%]), TP53 (22 [36%]), GNAS (17 [28%]), SMAD4 (11 [18%]), PIK3CA (10 [16%]), APC (9 [15%]), ATM (8 [13%]), BRAF (5 [8%]), KIT (5 [8%]), NRAS (3 [5%]) and MET (3 [5%]). GNAS mutations frequently co-occurred with KRAS mutations (42% v 5%, OR 14.3, P < 0.001). No GA was associated with grade, mucinous histology or overall survival (OS). Besides these mutations, we also found unusual cases with targetable mutations such as ALK, EGFR, MET, IDH1 and ERBB2. In our comparative analyses, mutations in KRAS (p = 0.009), TP53 (p = 0.020), GNAS (p < 0.001) and APC (p < 0.001) genes were significantly different from CRC whereas there was no difference in prevalence of PIK3CA, SMAD4 and ATM genes. Conclusions: To date, our analysis of one of the largest cohorts of AAs, demonstrate a majority of AAs harbor at least 1 GAs. Although treatment paradigms in AAs are extrapolated from CRC, the molecular profile of these tumors differs significantly. Molecular characterization of these rare tumors is a necessary first step towards discovery of opportunities for use of targeted therapies in these patients.