Targeting TRIM29 As a Negative Regulator of CAR-NK Cell Effector Function to Improve Antitumor Efficacy of These Cells: A Perspective.

Natural killer (NK) cells are among the most important cells in innate immune defense. In contrast to T cells, the effector function of NK cells does not require prior stimulation and is not MHC restricted. Therefore, chimeric antigen receptor (CAR)-NK cells are superior to CAR-T cells. The complexity of the tumor microenvironment (TME) makes it necessary to explore various pathways involved in NK cell negative regulation. CAR-NK cell effector function can be improved by inhibiting the negative regulatory mechanisms. In this respect, the E3 ubiquitin ligase tripartite motif containing 29 (TRIM29) is known to be involved in reducing NK cell cytotoxicity and cytokine production. Also, targeting TRIM29 may enhance the antitumor efficacy of CAR-NK cells. The present study discusses the negative effects of TRIM29 on NK cell activity and genomic deletion or suppression of the expression of TRIM29 as a novel approach to optimize CAR-NK cell-based immunotherapy.

Efficacy and Feasibility of Adding Induction Chemotherapy to Neoadjuvant Chemoradiation in Locally Advanced Rectal Cancer: A Phase II Clinical Trial.

PURPOSE: Currently, neoadjuvant chemoradiation (CRT) followed by total mesorectal resection is considered the standard of care for treating locally advanced rectal cancer. This study aimed to investigate the efficacy and feasibility of adding induction chemotherapy to neoadjuvant CRT in locally advanced rectal cancer. METHODS: This phase-II clinical trial included 54 patients with newly diagnosed, locally advanced (clinical T3-4 and/or N1-2, M0) rectal cancer. All patients were treated with 3 cycles of preoperative chemotherapy using the XELOX (capecitabine + oxaliplatin) regimen before and after a concurrent standard long course of CRT (45-50.4 Gy) followed by standard radical surgery. Pathologic complete response (PCR) rate and toxicity were the primary and secondary endpoints, respectively. RESULTS: The study participants included 37 males and 17 females, with a median age of 59 years (range, 20-80 years). Twenty-nine patients (54%) had clinical stage-II disease, and 25 patients (46%) had clinical stage-III disease. Larger tumor size (P = 0.006) and distal rectal location (P = 0.009) showed lower PCR compared to smaller tumor size and upper rectal location. Pathologic examinations showed significant tumor regression (6.1 ± 2.7 cm vs. 1.9 ± 1.8 cm, P < 0.001) with 10 PCRs (18.5%) compared to before the intervention. The surgical margin was free of cancer in 52 patients (96.3%). Treatment-related toxicities were easily tolerated, and all patients completed their planned treatment without interruption. Grade III and IV toxicities were infrequent. CONCLUSION: The addition of induction chemotherapy to neoadjuvant CRT is an effective and well-tolerated treatment approach in patients with rectal cancer.

Insufficient lymph node assessment in gastric adenocarcinoma.

BACKGROUND: This study aimed to investigate the sufficient (≥ 16) lymph node assessment in 449 patients with gastric adenocarcinoma and literature review. METHODS: Four hundred and forty-nine patients with pathologically confirmed locoregional invasive gastric adenocarcinoma from 2004 to 2013 were included. A standard surgical resection was performed for all the patients with (n = 16) or without (n = 433) neoadjuvant treatment. RESULTS: In this study, 301 men and 148 women with a median age of 58 (range 21-88) years were included. The median total numbers of examined lymph nodes were 9 (range 0-55). Ninety-five patients (21.2%) had adequate (≥ 16) lymph node examination, and 70 patients (15.6%) had no examined lymph nodes. In univariate analysis, total or near total gastrectomy (P <  0.001), advanced node stage (P < 0.001), primary tumor size > 6 cm (P < 0.001), and the presence of perineural invasion (P = 0.039) were associated with more average number of examined lymph nodes. On multivariate analysis, node stage (P < 0.001) and type of surgery (P = 0.008) were independent predictive factors. CONCLUSION: In this study, approximately one in five patients with gastric adenocarcinoma had sufficient lymph node assessment. More studies are suggested for identifying a true inadequate lymph node dissection from insufficient lymph node assessment.

A comprehensive approach in high-grade glioma management: position statement from the Neuro-Oncology Scientific Club (NOSC), Shiraz, Iran.

Establishing a robust teamwork model in the practice of neuro-oncology requires continued interdisciplinary efforts. The Neuro-Oncology Scientific Club (NOSC) initiative is an interdisciplinary clinical forum promoting the comprehensive approach across involved disciplines in the management of central nervous system (CNS) malignancies. With its provincial founding panels and national steering board, NOSC has been operational in Iran since 2011. This initiative has pursued its mission through interval strategic meetings, tumor boards, case discussions as well as publishing neuro-oncology updates, case study periodicals, and newsletters. A provincial meeting of NOSC in Shiraz put together insights from international practice guidelines, emerging evidence, and expert opinions to draw a position statement on high-grade glioma management in adults. The present report summarizes key highlights from the above clinical forum.

Efficacy and Safety of Low-Dose-Rate Endorectal Brachytherapy as a Boost to Neoadjuvant Chemoradiation in the Treatment of Locally Advanced Distal Rectal Cancer: A Phase-II Clinical Trial.

PURPOSE: Despite advances in rectal cancer treatment over the last decade, local control and risk of late side effects due to external beam radiation therapy (EBRT) remain as concerns. The present study aimed to investigate the efficacy and the safety of low-dose-rate endorectal brachytherapy (LDRBT) as a boost to neoadjuvant chemoradiation for use in treating locally advanced distal rectal adenocarcinomas. METHODS: This phase-II clinical trial included 34 patients (as the study arm) with newly diagnosed, locally advanced (clinical T3-T4 and/or N1/N2, M0) lower rectal cancer. For comparative analysis, 102 matched patients (as the historical control arm) with rectal cancer were also selected. All the patients were treated with LDRBT (15 Gy in 3 fractions) and concurrent chemoradiation (45-50.4 Gy). Concurrent chemotherapy consisted of oxaliplatin 130 mg/m(2) intravenously on day 1 plus oral capecitabine 825 mg/m(2) twice daily during LDRBT and EBRT. RESULTS: The study results revealed a significant differences between the study arm and the control arm in terms in the pathologic tumor size (2.1 cm vs. 3.6 cm, P = 0.001), the pathologic tumor stage (35% T3-4 vs. 65% T3-4, P = 0.003), and the pathologic complete response (29.4% vs. 11.7%, P < 0.028). Moreover, a significantly higher dose of EBRT (P = 0.041) was found in the control arm, and a longer time to surgery was observed in the study arm (P < 0.001). The higher rate of treatment-related toxicities, such as mild proctitis and anemia, in the study arm was tolerable and easily manageable. CONCLUSION: A boost of LDRBT can optimize the pathologic complete response, with acceptable toxicities, in patients with distal rectal cancer.

Small Cell Carcinoma of the Esophagus: Clinicopathological Features and Outcome of 22 Cases.

BACKGROUND: Small cell esophageal carcinoma (SCEC) is a highly aggressive and rare neoplasm. OBJECTIVES: This study aimed to report the characteristics, prognostic factors, and treatment outcomes of 22 patients with SCEC. PATIENTS AND METHODS: This brief report was carried out by reviewing the medical records of 22 patients with newly histologically proven SCEC that were treated between 2000 and 2010 at 2 tertiary academic hospitals. All the potential prognostic variables, including the patients' characteristics, tumor features, and treatment modalities were analyzed to establish their influence on the patients' survival rates. RESULTS: This study was conducted on 7 males and 15 females with a median age of 61 years. Dysphagia and weight loss were the most prevalent symptoms. According to the results, 14 patients (64%) had limited diseases and 8 cases (36%) had extensive diseases. In those with extensive diseases, liver, lung, and lymph nodes (LNs) were the most metastatic sites. Besides, most tumors were located in lower (50%) and middle (32%) part of the esophagus. Most patients (91%) were treated with sequential (55%) or concurrent (36%) chemoradiation (CRT). Surgical resection was also performed for 7 patients. Chemotherapy regimen consisted of cisplatin and etoposide in 14 patients (64%). The median follow up time was 12 months. The 1, 3, and 5-year overall survival rates were 27%, 14%, and 4%, respectively. Yet, no prognostic factors were found because of the small sample size of the study. CONCLUSIONS: Primary SCEC is a rare and highly aggressive tumor. However, prognosis is poor and long-term survival is exceptional. CRT could be an appropriate alternative to operation.

Lymph Node Metastasis in Gastrointestinal Stromal Tumor (GIST): to Report a Case.

The Gastrointestinal Stromal Tumor (GIST) is a rare mesenchymal tumor of gastrointestinal (GI) tract. This tumor has tendency to liver metastasis and peritoneal recurrence, however; the primarily lymph node involvement or metastasis is rare. Here we reported a 17-years-old girl with multifocal gastric GIST and multiple lymph node involvement at presentation and recurrence in celiac lymph nodes. We also review some case reports on lymph node metastasis in GIST.

Vascular endothelial growth factor (VEGF) improves the sensitivity of CA125 for differentiation of epithelial ovarian cancers from ovarian cysts.

BACKGROUND: The present study aimed to compare the diagnostic value of preoperative serum levels of CA125 and vascular endothelial growth factor (VEGF), and the combination of both biomarkers for differentiating early stage epithelial ovarian cancers from ovarian cysts. MATERIALS AND METHODS: In this study, preoperative and postoperative serum levels of CA125 and VEGF of 30 patients with epithelial ovarian cancers (cancer arm) compared with that of 30 patients with benign ovarian cysts (cyst arm). Initial eligibility included having an ovarian cystic or solid mass detected by transvaginal ultrasonography at the hospital clinic. Included patients had to have localized pelvic disease and no clinical or imaging evidence of extrapelvic disease, ascites and distant metastasis. Initial exclusion criteria included prior history of malignancy or any type of cancer treatment. After surgery, only patients with pathologic diagnosis of early stage epithelial ovarian cancer and ovarian cyst were included. RESULTS: Preoperative serum levels of CA125 (P < 0.001) and VEGF (P < 0.001) were significantly higher in the study arm compared to the control arm. In addition, postoperative serum levels of CA125 (P < 0.001) and VEGF (P < 0.001) in study arm were significantly decreased compared to preoperative serum levels. At usual clinical cut-off levels of 17.6 pg/ml for VEGF and 35 U/ml for CA125, the sensitivity and specificity for detecting early stage epithelial ovary cancer were 90 and 57 % for VEGF and 66.6 and 73 % for CA125, respectively. At 100 % specificity for each test, the addition of VEGF to CA125 increased the sensitivity of early ovarian cancer detection from 60 to 73.3 %. CONCLUSION: This study indicates that the addition of VEGF serum value improves the specificity and the sensitivity of CA125 to detect early stage epithelial ovarian cancers, and to differentiate these neoplasms from ovarian cyst.

Treatment outcome and prognostic factors of adult glioblastoma multiforme.

INTRODUCTION: This study aimed to report the characteristics, prognostic factors and treatment outcome of 223 patients with glioblastoma multiforme (GBM). SUBJECTS AND METHOD: This retrospective study was carried out by reviewing the medical records of 223 adult patients diagnosed at a tertiary academic hospital between 1990 and 2008. Patients' follow up ranged from 1 to 69 months (median 11 months). Surgery was attempted in all patients in whom complete resection in 15 patients (7%), subtotal resection in 77 patients (34%), partial resection in 73 patients (33%) and biopsy alone in 58 patients (26%) were done. In addition, we performed a literature review of PubMed to find out and analyze major related series. In all, we collected and analyzed the data of 33 major series including more than 11,000 patients with GBM. RESULTS: There were 141 men and 82 women. The median progression free- and overall survival were 6 (95% CI=5.711-8.289) and 11 (95% CI=9.304-12.696) months respectively. In univariate analysis for overall survival, age (P=0.003), tumor size (P<0.013), performance status (P<0.001), the extent of surgical resection (P=0.009), dose of radiation (P<0.001), and adjuvant chemotherapy (P<0.001) were prognostic factors. However, in multivariate analysis, only radiation dose, extent of surgical resection, and adjuvant chemotherapy were independent prognostic factors for overall survival. CONCLUSION: The prognosis of adult patients with GBM remains poor; however, complete surgical resection and adjuvant treatments improve progression-free and overall survival.

Very late relapse in breast cancer survivors: a report of 6 cases.

BACKGROUND: Breast cancer is the most common cancer and the leading cause of cancer death among the women worldwide. The risk of local and distant recurrence is the highest during the first two years following the initial treatment. Very late relapse (after 12 years) is uncommon in breast cancer survivors. METHODS: Herein, we report the characteristics and outcomes of 6 such cases of breast cancer. RESULTS: The mean age of the patients was 40.1 years (range 30-57) and the mean disease free survival was 19.6 years. CONCLUSION: Late relapse is not so common in breast cancer but can occur in any stage. Therefore, we suggest life-time follow up for every patient with breast cancer.

Pediatric glioblastoma multiforme: A single-institution experience.

BACKGROUND: Glioblastoma multiforme (GBM) is the most common astrocytoma in adults and has a poor prognosis, with a median survival of about 12 months. But, it is rare in children. We report our experience on the pediatric population (20 years or younger) with GBM. PATIENTS AND METHODS: Twenty-three patients with GBM who were treated at our hospital during 1990-2008 were evaluated. RESULTS: The mean age was 15.2 years, and the majority of them (14/23) were male. All had received radiotherapy and some had also received chemotherapy. The mean survival was 16.0 months. Two cases survived more than 5 years. Age, radiation dose and performance status were significantly related to survival. CONCLUSION: GBM in pediatric patients were not very common in our center, and prognosis was unfavorable.

The efficacy and safety of neoadjuvant chemotherapy +/- letrozole in postmenopausal women with locally advanced breast cancer: a randomized phase III clinical trial.

This two-arm randomized clinical study aimed to evaluate the efficacy and safety of neoadjuvant concurrent chemotherapy and letrozole in postmenopausal women with locally advanced breast carcinoma. One hundred and one postmenopausal women aged 50-83 years with pathologically proven locally advanced (clinical stage T3, T4 and/or N2, N3) breast cancer were randomly assigned to receive neoadjuvant chemotherapy alone (control arm, n = 51) or neoadjuvant chemotherapy concurrent with letrozole 2.5 mg (study arm, n = 50). Chemotherapy consisted of a median 4 (range 3-5) cycles of intravenous 5-fluorouracil 600 mg/m(2), doxorubicin 60 mg/m(2), and cyclophosphamide 600 mg/m(2), every three weeks. All patients subsequently underwent modified radical mastectomy approximately two weeks after the last cycle of chemotherapy. Pathologic complete response rates were 25.5% and 10.2% in the study and the control group, respectively (P = 0.049). Similarly, clinical complete response rates were 27.6% and 10.2% in the study and the control group, respectively (P = 0.037). In the subgroup analysis of hormone receptor-positive cases, the complete response rates were more prominent in study group compared with control group. Common treatment-related side effects such as nausea, vomiting, bone marrow suppression, and mucositis were similar in both groups, but hot flush was more prevalent in study group compared with control group (P = 0.023). The addition of letrozole concurrently with neoadjuvant chemotherapy provides a higher clinical and pathologic response rates with acceptable toxicity compared with chemotherapy alone in postmenopausal women with locally advanced sensitive breast cancer.