Intratumoral HLA-DR-/CD33+/CD11b+ Myeloid-Derived Suppressor Cells Predict Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer.

Capecitabine-based neoadjuvant chemoradiation therapy (nCRT) is currently the mainstay of treatment for locally advanced rectal cancer (LARC), prior to surgical tumor removal. While response to this treatment is partial, it carries significant risk of side effects. As of today, there is no accepted model to predict tumor response, and allow for patient stratification. The level of circulating Myeloid-derived suppressor cells (MDSCs), a subpopulation of early myeloid cells (EMCs), has been shown to correlate with prognosis and response to therapy in advanced colon cancer, but their role in LARC is not clear. We sought to study the effect of intratumoral and circulating levels of different EMCs subpopulations including MDSCs on response to nCRT. We analyzed tumor, normal mucosa, and peripheral blood samples from 25 LARC patients for their different EMCs subpopulation before and after nCRT, and correlated them with degree of pathologic response, as determined postoperatively. In addition, we compared LARC patient to 10 healthy donors and 6 metastatic patients. CD33+HLA-DR-CD16-CD11b+EMCs in the circulation of LARC patients were found to inhibit T-cell activation. Furthermore, elevated levels of CD33+HLA-DR- myeloid cells were found in the tumor relative to normal mucosa, but not in the circulation when compared to healthy subjects. Moreover, intratumoral, but not circulating levels of MDSCs correlated with clinical stage and response to therapy in patients treated with nCRT, with high levels of MDSCs significantly predicting poor response to nCRT. Importantly, therapy by itself, had significant differential effects on MDSC levels, leading to increased circulating MDSCs, concomitantly with decreasing intratumoral MDSCs. Our results suggest that high levels of intratumoral, but not circulating MDSCs may confer drug resistance due to immunomodulatory effects, and serve as a biomarker for patient stratification and decision-making prior to nCRT.

Acne during adolescence did not predict skin rash reaction to cetuximab.

Cetuximab, a monoclonal antibody, is a part of the treatment for metastatic colorectal cancer. The most common side effect of cetuximab is skin rash, which has a similar distribution to acne vulgaris and some overlapping pathophysiological mechanisms. The aim of the current study was to determine whether acne vulgaris in adolescence (AinA) is predictive of a cetuximab-related rash to better understand the pathogenesis of this side effect and explore potential preventive actions. From July 2013 to June 2015, patients with metastatic colorectal cancer planned for treatment with cetuximab were enrolled in the study. Before initiating treatment, patients completed a questionnaire evaluating endocrine disorders, other chronic diseases, smoking, chronic medications, allergies, and dermatologic history of AinA and its severity. Patients were followed for 6 months. Data were collected from 32 participants (16 women, 16 men). Twenty-three (69%) patients experienced a cetuximab-associated skin reaction. Nine (28%) patients had a history of AinA. Of these, seven developed a cetuximab-associated skin reaction. Three of the five (60%) patients who used proton pump inhibitors (PPIs) developed severe (grades 3-4) skin toxicity versus 4/27 (15%) patients who were not on PPIs (P=0.057). The degree of skin toxicity correlated to the median time-to-tumor-progression: 2 months for patients with grades 0-1 compared with 5.5 months for grades 2-4 skin toxicity (P=0.047, 95% confidence interval 1.06-4.95). No significant correlation was found between AinA and cetuximab-associated skin reactions. The correlation between PPI treatment and severe skin toxicity related to cetuximab should be examined further.

Management of Inguinal Involvement of Peritoneal Surface Malignancies by Cytoreduction and HIPEC with Inguinal Perfusion.

BACKGROUND: Achieving complete cytoreduction of peritoneal surface malignancies (PSM) can be challenging. In most cases, delivery of heated intra-peritoneal chemotherapy (HIPEC) is straightforward. However, using the closed technique in some cases may be technically challenging; for example, in patients requiring abdominal closure using a large synthetic mesh. In cases where groin hernias are present, it is imperative to resect the hernia sac, since it may contain tumor deposits. In cases with major inguinal involvement where disease may spread out of the hernia sac or in cases where a hernia repair was performed while disease is present, inguinal perfusion should be considered. AIM: To describe our experience with combined intra-peritoneal and inguinal perfusion of HIPEC following cytoreductive surgery. PATIENTS AND METHODS: This is a retrospective review of all patients who underwent cytoreductive surgery (CRS) and HIPEC at our institution. A prospectively maintained database containing data of patients treated by CRS and HIPEC (n=122) was reviewed. All patients with macroscopic inguinal involvement by PSM with complete cytoreduction perfused by HIPEC were included. RESULTS: We identified five cases who underwent CRS and combined intraperitoneal and inguinal perfusion after resection of large inguinal tumor deposits (n=4) or after a recent hernia repair with hernial sac involvement by mucinous adenocarcinoma (n=1). All five patients were successfully perfused using an additional outflow catheter placed in the groin. DISCUSSION: In cases of inguinal involvement by PSM, complete cytoreduction should be achieved and perfusion of the involved groin considered as it is feasible and safe.

Resilience and psychosocial adjustment in digestive system cancer.

The study aims to investigate the contributions of resilience, affective reactions and post traumatic growth (PTG) to psychosocial adjustment and behavioral changes among digestive system cancer patients in Israel. A sample of 200 participants, 57.5 % men (from the 46 to 70-year age range), 1-4 years following diagnosis, completed an inventory assessing demographic and medical information, resilience, current positive affect (PA) and negative affect (NA), PTG, psychosocial adjustment and retrospective report of behavioral changes following cancer treatment. Resilience, PA and NA, and PTG were related to adjustment and/or reported behavioral changes, and PA, NA and PTG mediated some of the effects of resilience on adjustment and/or reported behavioral changes. The data underline the importance of resilience, affect, and PTG in the adjustment of digestive system cancer patients. Future studies are needed to better understand the associations of resilience with psychosocial adjustment and behavioral changes. This knowledge may help improve cancer survivors' adjustment.

The association of resilience and age in individuals with colorectal cancer: an exploratory cross-sectional study.

BACKGROUND: Studies generally report lower emotional distress in older patients with cancer than in younger patients with cancer. The personality construct of resilience was previously found to be higher with age, but has not been assessed in relation to emotional distress in older patients with cancer. OBJECTIVE: To assess the mediating effect of resilience on the associations between age and emotional distress in patients with colorectal cancer (CRC). PATIENTS AND METHODS: An exploratory cross-sectional study of 92 individuals, aged 27-87 years, diagnosed with CRC stage II-III, 1-5 years prior to enrollment in the study. They completed the Wagnild and Young's resilience scale and Brief Symptoms Inventory-18, cancer-related problem list, and demographic and disease-related details. RESULTS: Older age, male gender, and less cancer-related problems were associated with higher resilience and lower emotional distress. A Structural Equation Modeling (SEM) analysis and mediation tests showed that, while controlling for cancer-related problems, resilience mediated the effects of age and gender on emotional distress. CONCLUSIONS: The study enlarges the explanation for the consistent previous findings on the better adjustment of older patients with cancer. Increased professional support should be provided for patients with low resilience levels.

A first report of radioembolization for hepatic metastases from ocular melanoma.

BACKGROUND: Ocular melanoma (OM) metastasizes to the liver and is rapidly fatal despite aggressive therapy. Yttrium-90 microspheres (radioembolization) delivered via the hepatic artery is an established and effective approach for primary and metastatic hepatic tumors, although (90)Y use in OM has not been reported previously. METHODS: A retrospective review was performed for all patients with OM who received radioembolization at 5 centers. RESULTS: 11 patients received 12 treatments with a median activity of 1.55 GBq delivered per treatment. Toxicity was minimal, with PET/CT at 3 months posttreatment showing a response in all patients; 1 patient had a complete response. CONCLUSIONS: Radioembolization can control hepatic metastases of OM with very few side effects.

Severe toxicity related to the 5-fluorouracil/leucovorin combination (the Mayo Clinic regimen): a prospective study in colorectal cancer patients.

The Mayo Clinic regimen of leucovorin 20 mg/m followed immediately by 5-fluorouracil 425 mg/m administered for 5 consecutive days every 4 weeks is commonly used in the treatment of colorectal cancer. This study was aimed at prospectively determining the incidence and pattern of severe toxicity associated with this regimen. We evaluated prospectively 243 patients with colorectal cancer treated in our department with the Mayo Clinic regimen for the incidence of severe toxicity (defined as toxicity requiring hospitalization). Of the 243 patients, 32 (13%) were hospitalized for chemotherapy-related toxicity. Major toxicities included neutropenic fever in 21 (9%), grade III/IV mucositis in 25 (10%) and grade III/IV diarrhea in 20 (8%). There were five (2%) treatment-related deaths. Female patients exhibited a higher incidence of severe toxicity (18%) and toxic death (4/105) than did male patients (9% and 1/138, respectively). Elderly patients (> or =70 years) had a higher incidence of severe toxicity than younger patients did (24% versus 7%, < 0.001). Toxic death occurred in 4 of 89 patients aged 70 years or more compared to 1 of 154 in younger patients. Most episodes of severe toxicity (56%) and toxic deaths (4/5) were observed after the first cycle. We conclude that the Mayo Clinic regimen can be associated with severe toxicity, usually occurring after the first cycle. Female gender and advanced age predict severe toxicity; therefore, dose reduction in high-risk patients should be considered, especially during the first cycle.