Neoadjuvant Chemotherapy Surgery Research Articles

Tumor-Specific Imaging with Angiostamp800 or Bevacizumab-IRDye 800CW Improves Fluorescence-Guided Surgery over Indocyanine Green in Peritoneal Carcinomatosis

Complete surgical removal of lesions improves survival of peritoneal carcinomatosis and can be enhanced by intraoperative near-infrared fluorescence imaging. Indocyanine green (ICG) is the only near-infrared fluorescent dye approved for clinical use, but it lacks specificity for tumor cells, highlighting the need for tumor-selective targeting agents. We compared the tumor-specific near-infrared fluorescent probes Bevacizumab-IRDye 800CW and Angiostamp800, which target tumor angiogenesis and cancer cells, to ICG for fluorescence-guided surgery in peritoneal carcinomatosis of ovarian origin. The probes were administered to mice with orthotopic peritoneal carcinomatosis prior to conventional and fluorescence-guided surgery. The influence of neoadjuvant chemotherapy was also assessed. Conventional surgery removed 88.0 ± 1.2% of the total tumor load in mice. Fluorescence-guided surgery allowed the resection of additional nodules, enhancing the total tumor burden resection by 9.8 ± 0.7%, 8.5 ± 0.8%, and 3.9 ± 1.2% with Angiostamp800, Bevacizumab-IRDye 800CW and ICG, respectively. Interestingly, among the resected nodules, 15% were false-positive with ICG, compared to only 1.4% with Angiostamp800 and 3.5% with Bevacizumab-IRDye 800CW. Furthermore, conventional surgery removed only 69.0 ± 3.9% of the total tumor burden after neoadjuvant chemotherapy. Fluorescence-guided surgery with Angiostamp800 and Bevacizumab-IRDye 800CW increased the total tumor burden resection to 88.7 ± 4.3%, whereas ICG did not improve surgery at all. Bevacizumab-IRDye 800CW and Angiostamp800 better detect ovarian tumors and metastases than the clinically used fluorescent tracer ICG, and can help surgeons completely remove tumors, especially after surgery neoadjuvant chemotherapy.

The Impact of Prolonged Chemotherapy to Surgery Interval and Neoadjuvant Radiotherapy on Pathological Complete Response and Overall Survival in Pancreatic Cancer Patients.

Background:We aimed to study the impact of neoadjuvant chemotherapy to surgery (NCT-S) interval and neoadjuvant radiotherapy (NRT) on pathological complete response (pCR) and overall survival (OS) in pancreatic cancer (pancreatic ductal adenocarcinoma [PDAC]).Methods:National Cancer Data Base (NCDB)–pancreatectomy patients who underwent NCT/NRT were included. The NCT-S interval was divided into time quintiles in weeks: 8 to 11, 12 to 14, 15 to 19, 20 to 29, and >29 weeks.Results:A total of 2093 patients with NCT were included with median follow-up of 74 months and 71% NRT. The pCR rate was 2.1% with higher median OS compared with non-pCR (41 vs 19 months, P = .03). The pCR rate increased with longer NCT-S interval (quintiles: 1%, 1.6%, 1.7%, 3%, and 6%, P < .001, respectively). In logistic regression, NRT (odds ratio [OR] = 2.5, 95% confidence interval [CI]: 1.1-6.1, P = .03) and NCT-S >29 weeks (OR = 6.1, 95% CI = 2.02-18.50, P < .001) were predictive of increased pCR. The prolonged NCT-S interval and pCR were independent predictors of OS, whereas NRT was not.Conclusions:Longer NCT-S interval and pCR were independent predictors of improved OS in patients with PDAC. The NRT predicted increased pCR but not OS.

Pathological complete response to chemotherapy in pancreatic cancer: frequency, predictors and impact on overall survival

Background: While Pathological complete response (pCR) after neoadjuvant chemotherapy (NCT) in pancreatic cancer has been associated with improved overall survival (OS), the rate of pCR and its predictors have not been elucidated yet. Our aim was to study factors predicting rate of pCR in a large data set and the impact on OS. Methods: Patients listed in the National Cancer Data Base from 1998 to 2011 were studied. We included patients with NCT followed by surgery. Demographics, cancer characteristics, and treatment modalities including NCT to surgery (NCT-S) interval were studied. Results: A total of 2093 patients were included. Mean age was 62, 51% were male, and 71% had neoadjuvant radiotherapy (NRT). NCT-S was divided into time quintiles in weeks: 8–11, 12–14, 15–19, 20–29 and >29 weeks; as well as a continuous variable). Median follow up was 74 months. Rate of pCR was 2.1% (44/2093). OS in pCR vs non-pCR: 61 vs. 31 months, HR 0.3, 95% CI 0.1–0.9, p 0.03). There was a significant increase in pCR with longer NCT-S interval (quintiles: (5/510 = 1.0%, 9/551 = 1.6%, 8/462 = 1.7%, 12/403 = 3.0% and 10/167 = 6.0%, p < 0.001). In logistic regression: NRT (OR 2.5, 95% CI: 1.1–6.1, p = 0.03) and NCT-S interval per week increase (OR 1.1, 95% CI 1.03–1.09, p < 0.001) as well as NCT-S >29 weeks (OR 6.1, 95% CI 2.02–18.50, p < 0.001) were predictive of increased pCR rate. Multivariate Cox regression showed that age, pCR and NCT-S >29 weeks were significantly predictive of OS, while gender, race, facility type, tumor grade, cT, cN stage, single vs. multiple chemotherapy agents and NRT were not.. Conclusion: NCT-S interval >29 weeks and pCR were independent predictors of better OS in pancreatic cancer patients. NRT predicted increased pCR but not OS in the multivariate analysis. Further studies are needed to optimize multimodality regimens that best improve OS.

Adjuvant or neoadjuvant chemotherapy in early-stage non-small cell lung cancer (NSCLC): How would staging affect the patients (pts) treated?

7509 Background: Both adjuvant chemotherapy (ACT) (HR 0.89, Pignon 2006 ) and neoadjuvant chemotherapy (NCT) (HR 0.88, Gilligan 2007) appear to result in comparable survival benefit in pts with early stage NSCLC. ASCO currently recommends ACT for pts with completely resected stages pII-III NSCLC (Pisters, 2007), as the pooled benefit is largest in these stages. A formal large scale comparative trial between both approaches seems appropriate, albeit requiring a large sample size. We assume that the outcome of such a trial is likely to be confounded by clinicopathological stage migration, as the decision to give NCT is based on clinical staging, which is known to be inaccurate (D'Cunha, 2005). Methods: Exploratory analyses of the 463 pts (239 surgery alone (S), 224 NCT + surgery (NCT-S)) included in a large randomised trial investigating the role of platinum-based NCT (LU22-NVALT 2-EORTC 08012), in whom detailed clinical and pathological staging data [UICC-6, Mountain, 1997] is available, in order 1. to estimate the directions and magnitude of clinicopathological stage migration in pts with resectable NSCLC. 2. to assess its impact on the selection of pts receiving NCT or ACT according to the ASCO-guideline. Results: Clinical staging is well balanced between both treatment arms. Stage migration per stage and treatment arm is shown in the Table. 36% of S-pts and 25% of CT-S pts migrate up and 15% and 20% down, respectively. Applying the ASCO guideline, 119 (50%) S pts who had pathological stage II/III would receive ACT. However, the use of clinical staging to select pts for NCT would result in only 35% pts receiving this treatment. Conclusions: Besides the need for a large sample size, any future comparison between ACT and NCT in early stage NSCLC based on the current ASCO-guideline, will have to compensate for a selection bias by stage migration in favour of ACT. Clinical staging needs hence to be as accurate as possible. Clinical Staging S-pts (n= 239) NCT-S pts (n= 224) I II III I II III Pathological staging 0 0 0 0 5 (2%) 2 (1%) 1 (<1%) I 82 (34%) 26 (11%) 5 (2%) 95 (42%) 31 (14%) 6 (3%) II 34 (14%) 31 (13%) 5 (2%) 31 (14%) 19 (8%) 1 (<1%) III 26 (11%) 19 (8%) 4 (2%) 13 (6%) 11 (5%) 7 (3%) IV 2 (1%) 5 (2%) 0 2 (1%) 0 0 Total 144 (60%) 81 (34%) 14 (6%) 146 (65%) 63 (28%) 15 (7%) Figures are numbers and (%) of each treatment arm No significant financial relationships to disclose.

Radiopaque coil insertion into breast cancers prior to neoadjuvant chemotherapy

Between May 1998 and December 2002, neoadjuvant chemotherapy was given to 81 women aiming to reduce tumour size and avoid mastectomy. A coil was inserted under ultrasound guidance into the tumour before treatment started. The impact of coil placement on subsequent surgery was assessed prospectively. Clinical response was seen in 69 patients and breast conservation was achieved in 60 cases. In 19 cases (23%) mammography and ultrasound were normal and localization was achieved exclusively by use of the coil. Eight of these 19 (10% of the total) had a complete pathological response; however in the remaining 11 cases (13%) there was residual invasive cancer. This study suggests that in patients undergoing neoadjuvant chemotherapy surgery is still appropriate even when clinical response appears complete. The use of the coil identifies 13% of patients with otherwise undetectable residual disease and is a valuable guide in identifying the site for further surgery.