Ex Vivo Drug Screening Informed Targeted Therapy for Metastatic Parotid Squamous Cell Carcinoma.

The purpose of ex vivo drug screening in the context of precision oncology is to serve as a functional diagnostic method for therapy efficacy modeling directly on patient-derived tumor cells. Here, we report a case study using integrated multiomics ex vivo drug screening approach to assess therapy efficacy in a rare metastatic squamous cell carcinoma of the parotid gland. Tumor cells isolated from lymph node metastasis and distal subcutaneous metastasis were used for imaging-based single-cell resolution drug screening and reverse-phase protein array-based drug screening assays to inform the treatment strategy after standard therapeutic options had been exhausted. The drug targets discovered on the basis of the ex vivo measured drug efficacy were validated with histopathology, genomic profiling, and in vitro cell biology methods, and targeted treatments with durable clinical responses were achieved. These results demonstrate the use of serial ex vivo drug screening to inform adjuvant therapy options prior to and during treatment and highlight HER2 as a potential therapy target also in metastatic squamous cell carcinoma of the salivary glands.

Surgical care quality and oncologic outcome after D2 gastrectomy for gastric cancer.

AIM: To examine the quality of surgical care and long-term oncologic outcome after D2 gastrectomy for gastric cancer. METHODS: From 1999 to 2008, a total of 109 consecutive patients underwent D2 gastrectomy without routine pancreaticosplenectomy in a multimodal setting at our institution. Oncologic outcomes together with clinical and histopathologic data were analyzed in relation to the type of surgery performed. Staging was carried out according to the Union for International Cancer Control criteria of 2002. Patients were followed-up for five years at the outpatient clinic. The primary measure of outcome was long-term survival with the quality of surgery as a secondary outcome measure. Clinical data were retrospectively collected from the patient records, and causes of death were obtained from national registries. RESULTS: A total of 109 patients (58 men) with a mean age of 67.4 ± 11.2 years underwent total gastrectomy or gastric resection with D2 lymph node dissection. The tumor stage distribution was as follows: stage I, (27/109) 24.8%; stage II, (31/109) 28.4%; stage III, (41/109) 37.6%; and stage IV, (10/109) 9.2%. Forty patients (36.7%) received chemotherapy or chemoradiotherapy. The five-year overall survival rate for all 109 patients was 45.0%, and was 47.1% for the 104 patients treated with curative R0 resection. The five-year disease-specific survival rates were 53.0% and 55.8%, respectively. In a multivariate analysis, body mass index and tumor stage were independent prognostic factors for overall survival (both P < 0.01), whereas body mass index, tumor stage, tumor site, Lauren classification, and lymph node invasion were prognostic factors for cancer-specific survival (all P < 0.05). Postoperative 30-d mortality was 1.8% and 30-d, surgical (including three anastomotic leaks, two of which were treated conservatively), and general morbidities were 26.6%, 12.8%, and 14.7%, respectively. CONCLUSION: D2 dissection is a safe surgical option for gastric cancer, providing quality surgical care and long-term oncologic outcomes that are in line with current Western standards.

Short- and long-term outcome following laparoscopic versus open resection for carcinoma of the rectum in the multimodal setting.

BACKGROUND: Laparoscopic resection for rectal cancer has remained controversial because of the lack of level 1 evidence regarding oncologic safety and long-term survival. OBJECTIVES: The aim of this study was to assess the impact of laparoscopic versus open resection for rectal cancer on clinical and oncologic outcome in the multimodal setting. DESIGN: This is a review of prospectively gathered data from a single-institution rectal cancer database. SETTINGS: This study was conducted in the Central Hospital of Central Finland. PATIENTS: From January 1999 to December 2006, 191 selected patients were included. INTERVENTIONS: One hundred patients underwent laparoscopic resection, and 91 patients, also suitable for laparoscopic surgery, underwent open major rectal resection in the multimodal setting. MAIN OUTCOME MEASURES: The main measures of outcome were early recovery and short- and long-term morbidity; local recurrence and survival were secondary outcomes. LIMITATIONS: This is not a randomized study. RESULTS: The study groups were balanced for baseline characteristics. Conversion rate to open surgery was 22%. Laparoscopic surgery resulted in significantly less bleeding (175 mL vs 500 mL, p < 0.001), 1 day earlier recovery of normal diet (3 days vs 4 days, p = 0.001), and shorter postoperative hospital stay (7 days vs 9 days, p < 0.001). Postoperative 30-day mortality (1% vs 3%), morbidity (31% vs 43%), readmission (11% vs 15%), and reoperation (6% vs 9%) rates were similar in the 2 groups, but significantly fewer patients in the laparoscopic group had long-term complications (19% vs 36%, p = 0.033). The 5-year disease-free survival (78% vs 80%, p = 0.74) and local recurrence (5% vs 6%, p = 0.66) rates were similar in the laparoscopic and open group for those 175 patients treated for cure. CONCLUSION: Laparoscopic surgery resulted in faster postoperative recovery and fewer long-term complications than open surgery without apparently compromising the long-term oncologic outcome. Our results indicate that laparoscopic rectal resection is an acceptable alternative to open surgery in selected patients with rectal cancer.

Quality of surgical care, local recurrence, and survival in patients with low- and midrectal cancers following multimodal therapy.

PURPOSE: To assess the quality of surgical care and outcome following multimodal treatment for low- and midrectal cancers, focusing on differences between low anterior and abdominoperineal resections. METHODS: From 1999 to 2007, 179 patients underwent low anterior resection (LAR), abdominoperineal resection (APR), or proctocolectomy for low- or midrectal cancers. Preoperative (chemo)radiotherapy was given according to local guidelines and adjuvant postoperative chemotherapy in stage III disease. Outcome together with clinical and histopathological data were analyzed in relation to the type of surgery performed. RESULTS: The postoperative mortality was 2.2%; morbidity, 39.6%; reoperation rate, 8.4%; and readmission rate, 16.0%. Involved circumferential resection margin (CRM ≤ 1 mm) rate was 4.5% (APR 9.1% vs. LAR 2.6%, p = 0.046). Intraoperative bowel perforation occurred in 5.5% of APRs. Anastomotic leak rate was 15.3%. The 5-year overall survival of the 179 patients was 68.5 %; disease-specific survival, 82.2%; and local recurrence rate, 6.3%. The overall, disease-specific, and disease-free survival rates in the 162 patients treated for cure were 73.1%, 84.6%, and 78.3%, and local recurrence rate was 4.4% with no significant differences between LAR and APR. CRM was the only independent predictor of local recurrence and CRM, tumor stage, and level independent predictors of disease-free survival. CONCLUSIONS: Quality of surgical care was in line with the current international standards. CRM was an independent predictor for local recurrence and CRM, tumor stage, and level independent prognostic factors for disease-free survival. Neither the type of surgery (LAR vs. APR) nor the surgical approach (laparoscopic vs. open) influenced the oncologic outcome.