Preliminary results of a cohort study of induction chemotherapy-based treatment for locally recurrent rectal cancer.

BACKGROUND: A significant number of patients treated for locally recurrent rectal cancer have local or systemic failure, especially after incomplete surgical resection. Neoadjuvant treatment regimens in patients who have already undergone preoperative (chemo)radiotherapy for the primary tumour are limited. The objective of the present study was to evaluate the influence of a neoadjuvant regimen incorporating induction chemotherapy (ICT) in patients with locally recurrent rectal cancer who had preoperative (chemo)radiotherapy for the primary cancer or an earlier local recurrence. METHODS: Patients were treated with a sequential neoadjuvant regimen including three or four cycles of 5-fluorouracil and oxaliplatin-containing chemotherapy. When no progressive disease was found at evaluation, neoadjuvant treatment was continued with chemoradiation therapy (CRRT) using 30 Gy with concomitant capecitabine. If there was a response to ICT, the patient was advised to continue with systemic chemotherapy after CRRT as consolidation chemotherapy while waiting for resection. These patients were compared with patients who received CRRT alone in the same time interval. RESULTS: Of 58 patients who had ICT, 32 (55 per cent) had surgery with clear resection margins, of whom ten (17 per cent) exhibited a pathological complete response (pCR). The remaining 26 patients had 23 R1 and three R2 resections. In 71 patients who received CRRT, a similar rate of R0 (35 patients) and R1 (36) resection was found (P = 0·506), but only three patients (4 per cent) had a pCR (P = 0·015). CONCLUSION: The incorporation of ICT in neoadjuvant regimens for locally recurrent rectal cancer is a promising strategy.

Results of a pooled analysis of IOERT containing multimodality treatment for locally recurrent rectal cancer: Results of 565 patients of two major treatment centres.

OBJECTIVE: Aim of this study is analysing the pooled results of Intra-Operative Electron beam Radiotherapy (IOERT) containing multimodality treatment of locally recurrent rectal cancer (LRRC) of two major treatment centres. METHODS AND MATERIALS: Five hundred sixty five patients with LRRC who underwent multimodality-treatment up to 2010 were studied. The preferred treatment was preoperative chemo-radiotherapy, surgery and IOERT. In uni- and multivariate analyses risk factors for local re-recurrence, distant metastasis free survival, relapse free survival, cancer-specific survival and overall survival were studied. RESULTS: Two hundred fifty one patients (44%) underwent a radical (R0) resection. In patients who had no preoperative treatment the R0 resection rate was 26%, and this was 43% and 50% for patients who respectively received preoperative re-(chemo)-irradiation or full-course radiotherapy (p < 0.0001). After uni- and multivariate analysis it was found that all oncologic parameters were influenced by preoperative treatment and radicality of the resection. Patients who were re-irradiated had a similar outcome compared to patients, who were radiotherapy naive and could undergo full-course treatment, except the chance of local re-recurrence was higher for re-irradiated patients. Waiting-time between preoperative radiotherapy and IOERT was inversely correlated with the chance of local re-recurrence, and positively correlated with the chance of a R0 resection. CONCLUSIONS: R0 resection is the most important factor influencing oncologic parameters in treatment of LRRC. Preoperative (chemo)-radiotherapy increases the chance of achieving radical resections and improves oncologic outcomes. Short waiting-times between preoperative treatment and IOERT improves the effectiveness of IOERT to reduce the chance of a local re-recurrence.

Optomechanical coupling between a multilayer graphene mechanical resonator and a superconducting microwave cavity.

The combination of low mass density, high frequency and high quality factor, Q, of mechanical resonators made of two-dimensional crystals such as graphene make them attractive for applications in force/mass sensing and exploring the quantum regime of mechanical motion. Microwave optomechanics with superconducting cavities offers exquisite position sensitivity and enables the preparation and detection of mechanical systems in the quantum ground state. Here, we demonstrate coupling between a multilayer graphene resonator with quality factors up to 220,000 and a high-Q superconducting cavity. Using thermomechanical noise as calibration, we achieve a displacement sensitivity of 17 fm Hz(-1/2). Optomechanical coupling is demonstrated by optomechanically induced reflection and absorption of microwave photons. We observe 17 dB of mechanical microwave amplification and signatures of strong optomechanical backaction. We quantitatively extract the cooperativity C, a characterization of coupling strength, from the measurement with no free parameters and find C = 8, which is promising for the quantum regime of graphene motion.

Feasibility of reirradiation in the treatment of locally recurrent rectal cancer.

BACKGROUND: Many patients with locally recurrent rectal cancer receive radiotherapy for the treatment of the primary tumour. It is unclear whether reirradiation is safe and effective when a local recurrence develops. The aim of this study was to evaluate the toxicity and oncological outcome of reirradiation in patients with locally recurrent rectal carcinoma. METHODS: From March 1994 until December 2013, data on patients with locally recurrent rectal cancer (without distant metastasis) were entered into a database. Patients were reirradiated with a reduced dose of 30 Gy and received an intraoperative electron radiotherapy boost during surgery. Morbidity associated with radiotherapy, postoperative complications and oncological outcome were evaluated. RESULTS: Clear margins (R0) were obtained in 75 (55·6 per cent) of the 135 patients who were reirradiated. Forty-six patients developed serious postoperative complications and the 30-day mortality rate was 4·6 per cent. Multivariable analysis showed that margin status was the main factor influencing oncological outcome (hazard ratio for overall survival 2·51 for R1 and 3·19 for R2 versus R0 resection; both P < 0·001). There was no significant difference in survival between the reirradiated group and a group of 113 patients who had full-course irradiation (5-year overall survival rate 34·1 and 39·1 per cent respectively; P = 0·278). Both reirradiation and full-course irradiation were associated with better survival than no irradiation in a historical control group of 24 patients (5-year overall survival rate 23 per cent; P = 0·225 and P = 0·062). CONCLUSION: Reirradiation (with concomitant chemotherapy) has few side-effects and complements radical resection of recurrent rectal cancer.

Abdominosacral resection: long-term outcome in 86 patients with locally advanced or locally recurrent rectal cancer.

AIMS: The purpose of this study is to evaluate the outcome of abdominosacral resections (ASR) in patients with locally advanced or recurrent rectal cancer. METHODS: From 1994 until 2012 patients with locally advanced rectal cancer (LARC) and locally recurrent rectal cancer (LRRC) underwent a curative ASR and were enrolled in a database. The postoperative complication rates, predictive factors on oncological outcome and survival rates were registered. RESULTS: Seventy-two patients with LRRC (mean age 63; 44 male, 28 female) and 14 patients with LARC (mean age 65; 6 male, 8 female) underwent ASR. R0 resection was achieved in 37 patients with LRRC and 11 patients with LARC. Twenty-seven patients underwent an R1 resection (3 in the LARC group). Eight patients had an R2 resection, compared to no patients in the LARC group. In respectively 26 and 1 patients of the LRRC and LARC groups a grade 3 or 4 complication occurred and the 30-days mortality rate was respectively 3% and 7%. The 5-years overall survival was 28% and 24% respectively. CONCLUSION: En bloc radical resection remains the primary goal in the treatment of dorsally located (recurrent) rectal cancer. After thorough patient selection, ASR is a safe procedure to perform, shows acceptable morbidity rates and leads to a good oncological outcome.

Development of mammalian embryos exposed to mixed-size nanoparticles.

Inhaled or ingested ultrafine nanoparticles and their effects on early pregnancy remain polemic. The objectives of the study were: (a) to determine the embryotoxic effects of nanoparticles at the 2-cell stage and (b) to localize the internalized nanoparticles in the blastocyst. Thawed mouse 2-cell embryos (no. = 128) were exposed to either mixed-size polystyrene-based nanoparticles (11 million/ml) or control G1.3 medium and assessed after 72 hours. Additionally, blastocysts (no. = 146) were exposed to nanoparticles and analyzed. The results showed that the nanoparticles did not inhibit 2-cell embryo development to the blastocyst stage (89.4 vs 96.8%; treated vs control). There were no differences in hatching (34.8 vs 43.5%), implantation (13.6 vs 24.2%) and degeneration (10.6 vs 3.2%). Delayed exposure to nanoparticles showed similar percent hatching (40.7 vs 47.3%) and implantation (17.6 vs 20.0%). Although nanoparticles were internalized, embryo development was not inhibited suggesting a lack of embryotoxicity. During hatching, the larger nanoparticles adhered to the extruding blastocyst, preferentially on trophoblasts, but interference was insignificant. Exposure to polystyrene-based nanoparticles at the concentration tested are not associated with embryonic loss.