Preoperative Radiotherapy Is Associated With Significant Survival Benefits for Patients With Gastric Signet Ring Cell Carcinoma: A SEER-Based Approach.

OBJECTIVE: To explore the clinical and pathological features of gastric signet ring cell carcinoma, and evaluate the survival impact of preoperative radiotherapy on these patients. METHODS: The Surveillance, Epidemiology, and End Results database was used to extract eligible patients from 2004 to 2015. The patients were divided into those with and without preoperative radiotherapy. The categorical variables were described by chi-square tests. The patients' survival was compared between the 2 groups by Kaplan-Meier method with log-rank tests. Cox proportional hazard model was adopted to identify prognostic factors of cancer-specific survival. RESULTS: Totally 4771 patients were recruited, of whom 218(4.6%) patients received preoperative radiotherapy, while 4553(95.4%) patients didn't receive this treatment. Survival analysis of the entire cohort demonstrated that preoperative radiotherapy improved both cancer-specific survival and overall survival (p < 0.001) of the patients. Cox proportional hazard models identified age >60, tumor size >50 mm, TNM stage II-IV as independent risk factors for poor prognosis (HR > 1, p < 0.05). Notably, preoperative radiotherapy was identified as an independent protective factor for favorable prognosis (HR < 1, p < 0.05). Subgroup survival analysis showed that preoperative radiotherapy exerted significant survival benefits for the stages III and IV patients. CONCLUSIONS: In this population-based study, preoperative radiotherapy is associated with significant survival benefits for the patients with advanced gastric signet ring cell carcinoma. Hence preoperative radiotherapy is feasible for these patients.

Comparisons between the Dosimetric and Clinical Outcomes of Tomotherapy and 3D Conformal Radiotherapy in Gastric Cancer Treatment

Introduction: Previous studies comparing tomotherapy (TOMO) and three dimensional (3D) conformal radiotherapy (3DCRT) in gastric radiotherapy are limited and tend to be based on dosimetry. The aim of the present study was to evaluate the clinical outcomes of these two treatment modalities. Methods: A total of 51 patients diagnosed with gastric cancer who were treated with postoperative adjuvant chemoradiotherapy and had subtotal/total gastrectomy and D2 lymphatic dissection were recruited to the present study: 30 patients were treated with TOMO and 21 patients were treated with 3DCRT. Results: The 3DCRT and TOMO treatment regimens were compared. There was no difference in planning target volume (PTV) 95%, but TOMO was statistically significant in regard to PTV 105% (P<0.05). TOMO was also significantly different when compared with 3DCRT when evaluating liver mean dose, liver V40, right/left kidneys mean dose, right/left kidneys V20 and spinal cord mean dose values (P<0.05). Grade 2 acute side effects were more frequent (85.7%) following 3DCRT. In addition, the median overall survival time for TOMO treated patients was 62 months while in 3DCRT treated patients it was 22.05 months. The difference in disease free survival was also significantly increased in patients treated with TOMO (66.7% vs. 19.0%; P<0.05). Conclusion: TOMO treatment resulted in lower acute side effects with better patient survival following gastric cancer radiotherapy.

Signet-ring cell adenocarcinoma of unknown primary presenting with superior vena cava (SVC) syndrome: rare type of cancer.

A 53-year-old man presented with a 3-month history of progressive, non-productive cough followed by occasional swelling of the face and upper extremities. Physical examination on admission revealed prominent superficial vessels at the neck and upper extremity swelling. Bronchoscopy revealed the superior segment of the right lower lobe was narrow but without visible mass; cell block and biopsy done revealed signet-ring cell carcinoma with an immunohistochemistry pattern favouring the primary site of malignancy as either gastric or of the pancreaticobiliary tree. However, CT scan of the abdomen and pelvis with triple contrast revealed only slight gastric wall thickening; the pancreas was unremarkable. The patient underwent radiotherapy with noted improvement of symptoms. He was then discharged with plans for further work-up on an outpatient basis. This work highlights the importance of a comprehensive histopathological and immunohistochemical work-up which can help predict a site of origin to be able to provide the appropriate management.

Preoperative radiotherapy improves survival in rectal signet-ring cell carcinoma-a population-based study.

BACKGROUND: To investigate the clinical value of preoperative and postoperative radiotherapy (RT) in patients with rectal signet-ring cell carcinoma (SRCC). METHODS: Using the Surveillance, Epidemiology, and End Results program patients with stage II-III rectal SRCC were retrospectively included between 1988 and 2012. Univariate and multivariate Cox regression analyses were performed to analyze the effect of preoperative and postoperative RT on cause-specific survival (CSS). RESULTS: A total of 292 patients were included: 138 patients received preoperative RT, 101 patients received postoperative RT, and 53 patients underwent surgery alone. Overall, 5- and 10-year CSS was 43.8 and 37.6%, respectively. Preliminary survival analysis demonstrated that preoperative RT improved CSS versus surgery alone, especially in patients with stage III disease. Multivariate analysis demonstrated that preoperative RT was independent predictors for CSS in stage III rectal SRCC. CSS in preoperative and postoperative RT groups was comparable. CONCLUSIONS: Preoperative RT significantly improved survival outcomes in patients with stage III rectal SRCC.

Negative lymph node count is an independent prognostic factor for patients with rectal cancer who received preoperative radiotherapy.

BACKGROUND: Negative lymph node (NLN) count has been reported to provide more accurate prognostic information than the N stage alone in patients with rectal cancer (RC). Since preoperative radiotherapy (Pre-RT) can significantly affect the LN status, it is unclear whether NLN count still has prognostic value count on survival of patients with RC who received Pre-RT. METHODS: In this study, clinicopathological characteristics, number of positive LNs and survival time were collected from Surveillance, Epidemiology, and End Results Program (SEER)-registered RC patients. Univariate and multivariate Cox proportional hazards models were used to assess the risk factors for survival. RESULTS: X-tile plots identified 9 (P < 0.001) as the optimal cutoff NLN value to divide the patients into high and low risk subsets in terms of cause specific survival (CSS). NLN count was validated as independently prognostic factor in univariate and multivariate analysis (P < 0.001). Subgroup analysis showed that NLN count was an independently prognostic factor for patients with stage ypII (P = 0.002) and ypIII (P < 0.001). CONCLUSIONS: Our results firmly demonstrated that NLN count provides accurate prognostic information for RC patients with Pre-RT.

Prognosis and value of preoperative radiotherapy in locally advanced rectal signet-ring cell carcinoma.

As well known, signet-ring cell carcinoma (SRCC) is a rare histological subtype of colorectal adenocarcinoma, which has been associated with poor prognosis and resistant to non-surgery therapy compared with common adenocarcinoma. In this study, we assessed the effect of preoperative radiotherapy (PRT) for locally advanced rectal SRCC in a large patient group from the Surveillance, Epidemiology, and End Results program (SEER, 1988-2011) database. SRCC was found in 0.9% (n = 622) rectal cancer (RC) patients in our study. In the PRT setting, SRCC had significantly worse cancer-specific survival than mucinous adenocarcinoma and nonmucinous adenocarcinoma patients (log-rank, P < 0.001). In terms of SRCC, stage III RC patients benefited from PRT (log-rank, P < 0.001) while stage II did not (P = 0.095). The multivariate Cox proportional hazard model showed that PRT was an independent benefit factor in stage III rectal SRCC patients (HR, 0.611; 95% CI, 0.407-0.919; P = 0.018). In conclusion, SRCC was an independent predictor of poor prognosis in stage III RC patients, but not in stage II. In the PRT setting of locally advanced RC, SRCC patients had significantly worse prognosis. PRT was an independent prognostic factor associated with improved survival in stage III rectal SRCC.

Percutaneous computed tomography-guided iodine-125 seeds implantation for unresectable pancreatic cancer.

BACKGROUND: To examine the safety and clinical efficacy of computed tomography (CT)-guided radioactive iodine-125 (125I) seeds implantation for patients with unresectable pancreatic cancer. MATERIALS AND METHODS: A group of 26 patients with pathologically confirmed unresectable pancreatic cancer underwent percutaneous CT-guided 125I seeds implantation. Part of them received transarterial chemotherapy and/or percutaneous transhepatic cholangial drainage before or after seeds implantation. The primary endpoints were the objective response rates, local control rates, and overall survival. RESULTS: CT scan 2 months after treatment revealed complete response (CR) in 8 patients, partial response (PR) in 9 patients. Overall response rate (CR + PR) is 65.38%. Local control rate was 88.46%. Median survival of the whole group was 15.3 months, whereas for Stage III and IV was 17.6 and 9.1 months, respectively. The estimated 1-year survival was 30.77%. CONCLUSIONS: We consider CT-guided 125I seeds implantation as a safe, effective, uncomplicated treatment for unresectable pancreatic cancer.

Adjuvant radiotherapy for gastric carcinoma: 10 years follow-up of 244 cases from a single institution.

BACKGROUND: Postoperative chemoradiotherapy (CRT) of gastric carcinoma improves survival among high- risk patients. This study was undertaken to analyse long-term survival probability and the impact of certain covariates on the survival outcome in affected individuals. MATERIALS AND METHODS: Between January 2000 and December 2005, 244 patients with gastric cancer underwent adjuvant radiotherapy (RT) in our institution. Data were retrieved retrospectively from patient files and analysed with SPSS version 21.0. RESULTS: A total of 244 cases, with a male to female ratio of 2.2:1, were enrolled in the study. The median age of the patients was 52 years (range, 20-78 years). Surgical margin status was positive or close in 72 (33%) out of 220 patients. Postoperative adjuvant RT dose was 46 Gy. Median follow-up was 99 months (range, 79-132 months) and 23 months (range, 2-155 months) for surviving patients and all patients, respectively. Actuarial overall survival (OS) probability for 1-, 3-, 5- and 10-year was 79%, 37%, 24% and 16%, respectively. Actuarial progression free survival (PFS) probability was 69%, 34%, 23% and 16% in the same consecutive order. AJCC Stage I-II disease, subtotal gastrectomy and adjuvant CRT were significantly associated with improved OS and PFS in multivariate analyses. Surgical margin status or lymph node dissection type were not prognostic for survival. CONCLUSIONS: Postoperative CRT should be considered for all patients with high risk of recurrence after gastrectomy. Beside well-known prognostic factors such as stage, lymph node status and concurrent chemotherapy, the type of gastrectomy was an important prognostic factor in our series. With our findings we add to the discussion on the definition of required surgical margin for subtotal gastrectomy. We consider that our observations in gastric cancer patients in our clinic can be useful in the future randomised trials to point the way to improved outcomes.

Evaluation of internal target volume in patients undergoing image-guided intensity modulated adjuvant radiation for gastric cancers.

OBJECTIVE: To evaluate three-dimensional (3D) displacements of gastric remnant during adjuvant radiation. METHODS: From January 2011 to September 2012, patients undergoing adjuvant image-guided intensity-modulated radiation on tomotherapy were included. Megavoltage CT (MVCT) data sets from daily treatment were coregistered with Day 1 MVCT. Residual stomach remnant was delineated on the data set, while the remaining were blinded to previous day contours. Gastric volume and centre of mass (COM) were determined for all data sets. The 3D deviation of COM was calculated for each fraction. Mean 3D and standard deviation (SD) were calculated for each patient and study population, and a 95% confidence interval (CI) was determined. Also, systematic and random errors for patient population and internal target volume (ITV) margin were calculated using the van Herk formula. RESULTS: There were 119 images available for 15 patients. Mean volume of remnant was 319 cm(3) (146-454 cm(3)). Gastric remnant expanded in different directions with no specific directional expansion. Average deviations in mediolateral, superoinferior and anteroposterior directions were 9 mm (3-25 mm; SD, 5 mm), 6 mm (3-16 mm; SD, 4 mm) and 5 mm (1-10 mm; SD, 3 mm), respectively, with 95% CI of 18, 15 and 11 mm, and ITV margins of 19.2, 13.5 and 7.8 mm, respectively. CONCLUSION: There is large variation in gastric remnant volume during the course of radiation. Large displacements observed in the present study necessitate the need to investigate adaptive techniques for optimizing intensity-modulated radiotherapy (IMRT) delivery. ADVANCES IN KNOWLEDGE: An adaptive strategy needs to be developed to optimize IMRT delivery for adjuvant gastric irradiation.

Continuous low-dose irradiation by I-125 seeds induces apoptosis of gastric cancer cells regardless of histological origin.

The efficacy of conventional radiation therapy for gastric cancer is controversial. In this study, we evaluated the in vitro and in vivo effects of continuous low-dose-rate irradiation by I-125 seeds on different histological types of gastric cancer cell lines. Three human gastric cancer cell lines (MKN74, MKN45, and NUGC4) were treated with or without continuous low-dose irradiation by I-125 seeds in vitro and in vivo. Cell viability, apoptosis, caspase-3 assay, and cell-cycle distribution were examined in vitro. Body weight and tumor volumes of BALB/c nude mice bearing MKN74, MKN45, and NUGC4 gastric cancer xenografts were measured, and in vivo cell proliferation and apoptosis assays were performed by Ki67 and TUNEL staining, respectively. Continuous low-dose-rate irradiation by I-125 seeds reduced cell viability and induced cell apoptosis through the activation of caspase-3, and led to the accumulation of cells in the G 2/M phase in vitro. It also suppressed the growth of gastric cancer xenografts in nude mice, while inhibiting cell proliferation and inducing apoptosis as demonstrated by Ki67 and TUNEL staining. Therefore, our data suggest that continuous low-dose-rate irradiation by I-125 seeds could be a promising new option for gastric cancer treatment, regardless of histological origin.

Uncorrectable ptosis: primary cutaneous signet-ring cell carcinoma.

Primary cutaneous signet-ring cell carcinoma (PCSRCC) is a rare but aggressive tumor. Our case highlights a 60-year-old man who presented with eyelid ptosis, for which he underwent multiple surgical procedures over a 3-year period prior to referral to our clinic. These procedures were complicated by scarring, delayed healing, and poor cosmetic outcome. In addition, the patient was noted to develop progressive enophthalmos. These concerning signs led to a CT scan and subsequent eyelid biopsy, which revealed a diagnosis of PCSRCC. Further management has involved an MRI and orbitotomy with biopsy revealing widespread extension of the carcinoma. Exenteration was performed to reduce the likelihood of metastasis. There are few documented case reports of PCSRCC of the eyelid in the literature. Of the 33 published cases of PCSRCC, 27 cases involve the eyelids and the other 6 cases involve the axilla. The unique clinical features of this case will be discussed, in particular the presentation as ptosis, an otherwise commonplace complaint in the oculoplastics clinic. The surgical course and histopathologic findings will be presented. The literature regarding PCSRCC will be reviewed including demographics, management, and prognosis. Although rare, PCSRCC follows an aggressive course with characteristically delayed diagnosis. Early identification and treatment likely offer a better prognosis. Thus, description of the clinical presentation of this rare tumor may aid in recognition and earlier treatment.

The therapeutic and adverse effects of modified radiation fields for patients with rectal cancer.

PURPOSE: To compare the therapeutic effect and complications of modified radiation fields (MRFs) with those of conventional pelvic radiation fields (CPRFs) for rectal cancer. METHODS AND MATERIALS: From December 1996 to October 2009, a total of 160 patients with rectal carcinoma who received total mesorectal excision and postoperative radiotherapy were examined. Ninety-four patients were in the CPRFs group, and 66 were in the MRFs group. The dose was 50 Gy per 25 fractions in the initial plan. RESULTS: The treatment volume and the volume of small bowel that received more than 15 Gy of the MRFs was smaller than that of the CPRFs (P < .001). The rates of local recurrence, overall survival, and disease-free survival were not statistically significant between the MRFs and CPRFs groups (P > .05). There was a statistical difference (P < .05) in the incidence of acute toxicity, which included serious complications in the lower digestive tract (grade ≥3). The completion rate for the initial radiotherapy plan was higher in the MRFs group than in the CPRFs group (P = .027). CONCLUSIONS: Compared with CPRFs, MRFs manifested a lower incidence of complications and the same therapeutic effects. This finding will facilitate the clinical application of MRFs for patients with rectal cancer.

Neoadjuvant radiochemotherapy and surgery for advanced rectal cancer : prognostic significance of tumor regression.

PURPOSE: Preoperative radiochemotherapy is widely used in the treatment of locally advanced rectal cancer. The predictive value of response to neoadjuvant treatment remains uncertain. We retrospectively evaluated the impact of downstaging and tumor regression as prognostic factors and its influence on the ability to perform sphincter-sparing surgery. PATIENTS AND METHODS: A total of 72 consecutive patients with advanced rectal cancer were included in this retrospective analysis. All patients were treated with preoperative 5-fluorouracil-based chemotherapy and pelvic radiation with a total dose of 50.4 Gy followed by surgery 6 weeks later. RESULTS: A sphincter-preserving procedure could be performed on 42 patients, and in all 72 patients complete resection (R0) was achieved. A pathological complete response (ypT0, ypN0) was achieved in 8 (11%) patients. None of the patients showing a complete pathological response relapsed or died during the follow-up period. At a median follow-up of 28 months, 65 patients were alive, none of these patients had local recurrence and 15 patients had metastatic disease. Patients showing a complete pathological response had a significantly better 2-year disease-free survival compared to patients with ≥10% residual tumor cells (p = 0.024). Patients < 65 years showed a significantly better response rate, compared with those > 65 years of age (p = 0.036). Acute toxicity was moderate. CONCLUSION: Preoperative radiochemotherapy is an effective and safe treatment for patients with locally advanced rectal cancer. Pathological parameters after preoperative radiochemotherapy, including tumor regression grading, could be correlated with disease-free survival. The impact of tumor regression grading needs to be further validated in prospective clinical trials.

Postoperative chemoradiation in patients with localized gastric adenocarcinoma: single center experience.

BACKGROUND: 5-Fluorouracil (FU)-based chemotherapy (CT) and concurrent 45 Gy radiotherapy (RT) is one of the standard postoperative approaches currently used in gastric carcinoma. The high toxicity rates of this treatment leads to interruption of treatment in the majority of patients. In our study, we investigated the rates of toxicity and treatment discontinuation observed during postoperative FU-based chemoradiotherapy (CRT); retrospectively evaluated the effect of CRT and the other prognostic factors on local and distant control and survival. PATIENTS AND METHODS: A total of 160 patients consisting of 97 total and 63 subtotal gastrectomy receiving postoperative CRT, have been studied retrospectively. RESULTS: Patients who had to discontinue the treatment for a median of 6 (range, 3-13) days experienced toxicity during treatment at a rate of 43%. During the 21 (range, 4-68) months of follow-up local recurrences were observed in 8 (5%) patients and distant recurrences were observed in 41 (25.6%) patients. While the 1-3 year overall survival (OS) rates were 75% and 42%, 13-year disease-free survival (DFS) rates were 63% and 42%, respectively. In the univariate analysis for OS and DFS demonstrated statistical significance for below those 60 years of age, D1-D2 dissection type, negative surgical margin, early treatment beginning, the absence of invasion, and early stage disease. D1D2 dissection type, early treatment beginning, age below 60 years and early stage disease significantly improve OS and DFS in multivariate analysis. CONCLUSIONS: Survival is worse in patients older than 60 years, had late treatment beginning, advanced stage and D0 dissection.

Signet ring cell histology and non-circumferential tumors predict pathological complete response following neoadjuvant chemoradiation in rectal cancers.

PURPOSE: Neoadjuvant chemoradiation followed by surgery is now the standard of care for patients with locally advanced rectal cancers. The aim of this study was to determine the rate of pathological complete response (pCR) following neoadjuvant treatment in patients with rectal cancers and identify the factors predicting the same. METHODS: We conducted a retrospective analysis of patients with rectal cancers treated with neoadjuvant therapy followed by surgery at our institution from 1993 to 2008. Patients who achieved pCR were identified. Various patient, tumor, and treatment-related factors were studied for their influence on pCR by univariate and multivariate analyses. The influence of pCR on survival was also studied but was restricted to patients with a minimum follow-up of 5 years. RESULTS: Between 1993 and 2008, 248 patients with rectal cancers received neoadjuvant therapy followed by surgery. Two hundred and twenty-seven patients received chemoradiation and 21 patients received only radiation. Pathological complete response was seen in 32 patients (12.9%). On multivariate analysis, the factors found to be independently predictive of pathological response were circumferential extent of the primary tumor (p = 0.016) and signet ring cell histology (p = 0.001). Among 116 patients with a minimum follow-up of 5 years, there was a trend towards increased overall survival (75% versus 54%) and reduced local recurrence (6.2% versus 12.3%) in the 16 patients who achieved a pCR compared to those who did not, even though the difference was not statistically significant. CONCLUSIONS: The factors that predict a pCR after neoadjuvant treatment for rectal cancers are absence of circumferential involvement and signet ring cell histology. Pathological complete response may confer an insignificant survival advantage.

Tonsillar metastasis of signet-ring cell adenocarcinoma of the colon.

Cases of primary colorectal signet-ring cell carcinoma metastatic to the tonsil are extremely rare. To the best of our knowledge, only 4 such cases have been previously reported in the literature. We report a new case in a 76-year-old white woman. She was treated with chemotherapy, but her disease continued to spread and she was eventually placed on comfort care and palliative radiation therapy. The manner in which tonsillar metastases evolve is still unknown, but some hypotheses have been proposed, and we briefly review these theories.

Preoperative staging of gastric cancer by endoscopic ultrasonography and multidetector-row computed tomography.

BACKGROUND AND AIM: The aim of this study was to determine the accuracy of endoscopic ultrasonography (EUS) and multidetector-row computed tomography (MDCT) for the locoregional staging of gastric cancer. EUS and computed tomography (CT) are valuable tools for the preoperative evaluation of gastric cancer. With the introduction of new therapeutic options and the recent improvements in CT technology, further evaluation of the diagnostic accuracy of EUS and MDCT is needed. METHODS: In total, 277 patients who underwent EUS and MDCT, followed by gastrectomy or endoscopic resection at Bundang Hospital, Seoul National University, from July 2006 to April 2008, were analyzed. The results from the preoperative EUS and MDCT were compared to the postoperative pathological findings. RESULTS: Among the 277 patients, the overall accuracy of EUS and MDCT for T staging was 74.7% and 76.9%, respectively. Among the 141 patients with visualized primary lesions on MDCT, the overall accuracy of EUS and MDCT for T staging was 61.7% and 63.8%, respectively. The overall accuracy for N staging was 66% and 62.8%, respectively. The performance of EUS and MDCT for large lesions and lesions at the cardia and angle had significantly lower accuracy than that of other groups. For EUS, the early gastric cancer lesions with ulcerative changes had significantly lower accuracy than those without ulcerative changes. CONCLUSIONS: For the preoperative assessment of individual T and N staging in patients with gastric cancer, the accuracy of MDCT was close to that of EUS. Both EUS and MDCT are useful complementary modalities for the locoregional staging of gastric cancer.