Cycles Of Preoperative Chemotherapy Research Articles

Perioperative chemotherapy in locally advanced gastric cancer in Chile: From evidence to daily practice.

92 Background: Gastric cancer is the leading cause of cancer death in Chile, with mortality rate of 26.7/100.000 in men, placing the country among the highest mortality rates worldwide. For locally advanced gastric cancer, a multimodality treatment is recommended, but in Chile, the treatment covered by the public health insurance, which assists more than 70% of the patients, is surgery alone. We conducted an observational study to assess efficacy and toxicity of perioperative chemotherapy (CT) in public hospitals in Chile (NCT01633203). Methods: Patients with locally advanced, operable gastric carcinoma, defined as presence of invasion of serosa or beyond (cT > 3 AJCC 2002) and/or lymph node metastasis (cN+) without distant metastasis (M0), were offered to receive preoperative CT with Epirubicin+Cisplatin+Capecitabine (ECX) regimen for 3 cycles followed by curative surgery with D2 lymphadenectomy. Staging abdominal CT scan was mandatory, laparoscopy was recommended. Patients with gastric retention, severe dysphagia or contraindications for CT were excluded. All patients signed the IRB approved informed consent form prior to enrolment. Data were collected using the OpenClinica platform. Results: Between August 2010 and March 2013, 110 patients were screened and 61 enrolled. Median age was 62 years (23-76 years) and most patients had good performance status at baseline (ECOG 0: 42, ECOG 1: 19). Tumor site was proximal in 24 (39%), medial in 16 (26%) and distal in 10 patients (16%). All but 4 patients (n = 57, 93%) completed three cycles of preoperative CT as planned. Fifty-five patients were operated and 54 (89%) had curative R0 resection. Of these, 36 (67%) had pT0-2, and 15 (28%) had pN0 tumors. A complete pathological response was found in 2 patients. Two patients were not operated for other reasons (one patient refused surgery and one patient presented a cerebrovascular accident during preoperative CT and died), and 5 patients (8%) progressed. As of September 1, 2015, 32 patients died. Three-year survival rate was 49%. Conclusions: Perioperative CT is feasible in public hospitals in Chile and should be offered as an alternative to primary surgery for patients with locally advanced gastric cancer.

Long-Term Survival Benefit and Potential for Cure after R1 Resection for Colorectal Liver Metastases.

Although efficient chemotherapy regimens have improved outcomes after R1 resection (positive margins) for colorectal liver metastases (CLMs), the long-term survival benefit and potential for cure after R1 resection have not been clearly demonstrated. The aim of this study was to evaluate the long-term outcome after R1 resection for CLM, and to identify factors predictive of cure. All resected CLM patients at our institution from 2000 to 2009 were prospectively evaluated. Cure was defined as a disease-free interval ≥5years from the last hepatic or extrahepatic resection to last follow-up. Of 628 patients consecutively resected for CLM, 428 were eligible for the study, of whom 219 (51%) underwent R0 resection (negative margins) and 209 (49%) underwent R1 resection. Overall, 130 patients with R0 resection and 141 patients with R1 resection had more than 5years of follow-up. Five- and 10-year overall survival rates were 56 and 34% for R0 patients, and 48 and 36% for R1 patients, respectively (p=0.37). Of the 141 patients who underwent R1 resection, 26 patients (18%) were considered 'cured', and 106 patients (75%) were considered 'noncured'. Independent predictive factors of cure after R1 resection included ≤10 total cycles of preoperative chemotherapy and objective response to preoperative chemotherapy. Overall, potential cure can be achieved in 18% of patients after R1 resection for CLM. The best conditions to achieve long-term survival after R1 resection rely on a good response to efficient and short first-line chemotherapy.

Predictors of Safety and Efficacy of 2-Stage Hepatectomy for Bilateral Colorectal Liver Metastases

In patients with bilateral colorectal liver metastases (CLM) not resectable in 1 operation, 2-stage hepatectomy is the standard surgical approach. The objective of this study was to determine factors associated with safety and efficacy of 2-stage hepatectomy. The study included all 109 patients for whom 2-stage hepatectomy for CLM was planned during 2003 to 2014. The RAS mutation status and other clinicopathologic factors were evaluated for association with major complications and survival using multivariate analysis. Two-stage hepatectomy was completed in 89 of 109 patients (82%). Reasons for dropout after the first stage were disease progression (n= 12), insufficient liver growth (n= 5), and complications after first stage or portal vein embolization (n= 3). More than 6 cycles of preoperative chemotherapy were associated with failure to proceed to the second stage (p= 0.009). Rates of major complications (26% vs 6%; p < 0.001) and 90-day mortality (7% vs 0%; p= 0.006) were higher after the second stage. The cumulative rate of major complications was 15% (n= 29). Factors independently associated with major complications were rectal primary tumor, metachronous CLM, and more than 1 lesion resected at first stage. At median follow-up of 29.5 months, 3-year (68% vs 6%; p < 0.001) and 5-year overall survival rates (49% vs 0%; p < 0.001) were better after 2-stage hepatectomy completion than noncompletion. Factors independently associated with poor overall survival were rectal primary tumor (p= 0.044), more than 5 CLMs (p= 0.043), need for chemotherapy after first stage (p= 0.046), and RAS mutation (p < 0.001). The RAS mutation independently predicts the oncologic efficacy of 2-stage hepatectomy and may help guide patient selection for this aggressive surgical strategy.

"Magic" of our gastric cancer results on perioperative chemotherapy.

To determine reproducibility of perioperative chemotherapy for gastric cancer (GC) on our settings by identifying patient's overall survival and comparing them to larger studies. Retrospective analysis of our series, where we present our eleven-year's experience on GC managed according to perioperative approach of three preoperative chemotherapy cycles followed by surgery and finally three postoperative chemotherapy cycles. Chemotherapic scheme used was Xelox (Oxaliplatin and Capecitabine). Epidemiologic parameters as well as surgical variables were analysed, presented, and compared to other series with similar approaches. Survival was estimated by Kaplan Meier/log rank method and also compared to these studies. Mean age was 65 years old. Overall survival in our series was 37.7%, similar to other groups using perioperative schemes. Mortality was 4% and morbidity 30%, which are also similar to those groups. Survival curves were compared to larger studies, finding similarities on them. Subgroup survival analysis between chemotherapy responders and non-responders didn't reach statically significant differences. Perioperative chemotherapic scheme can be reproduced on our setting with good results and without increasing morbidity or mortality.

The Evaluation of Liver Function and Surgical Influence by ICGR15 after Chemotherapy for Colorectal Liver Metastases.

Background; Approximately 60% of patients with colorectal cancer develop liver metastasis at some point after diagnosis. The aim of this study is to investigate whether the evaluation of ICGR15 preoperatively is a useful clinical indicator of hepatic injury following chemotherapy and to investigate the influence of multiple chemotherapies on liver function.Results; Mean ICGR15 values were higher in patients ≥65 years (P = 0.047) and in patients with ≥3 cycles (P = 0.022) and ≥6 cycles (P = 0.001) of systemic chemotherapy. ICGR15 values tended to be higher in patients with postoperative complications (P = 0.085). Patients receiving systemic chemotherapy for ≥6 cycles had higher levels of AST (P = 0.003), ALT (P = 0.015), and alkaline phosphatase (ALP) (P = 0.041). Patients receiving systemic chemotherapy for ≥3 cycles had higher levels of AST (P = 0.015) and ALP (P = 0.015).Conclusions; Because the pathological diagnosis is usually established only after operation, preoperative evaluation such as the identification of sinusoidal injury is difficult. Based on this study, higher ICGR15 values may provide an indication of surgical complications and be a predictor of liver dysfunction following frequent cycles of chemotherapy. Hepatectomy should be performed with the utmost care in such patients, and the number of cycles of preoperative chemotherapy should probably be as low as possible.

Combined stoma reversal and liver resection: a matched case–control study

BackgroundStoma reversal can be performed during liver resection (LR) in patients with colorectal liver metastases (CRCLM) whose primary colorectal tumor has been previously resected with a diverting loop ileostomy. This combined procedure is reputed to be associated with an increased morbidity. This study investigates the impact of simultaneous loop ileostomy closure (LIC) on the postoperative outcome of LR for CRCLM. MethodsFrom November 1996 to April 2012, 408 patients who underwent LR for CRCLM were retrospectively studied from a prospective database. Patients who underwent simultaneous LR and LIC were matched for the type of the main liver procedure, the use of preoperative chemotherapy and the need for greater than or equal to 6 cycles of preoperative chemotherapy with LR only patients. Intraoperative and postoperative complications were recorded and compared. ResultsTwenty-four patients (6%) with simultaneous LR and LIC were matched with 72 patients with LR only. Both groups were comparable for patients’ demographics and intraoperative findings. Liver related (P = .957) and overall postoperative morbidity (P = .643) rates did not differ between groups. ConclusionThe combined procedure appeared to be safe when strict surgical technique is used.

Interpretation and Prognostic Value of Positron Emission Tomography-Computed Tomography After Induction Chemotherapy With or Without Radiation in IIIA-N2 Non-small Cell Lung Cancer Patients Who Receive Curative Surgery.

We evaluate the correlation of clinical staging on positron emission tomography-computed tomography (PET-CT) and pathologic staging and the prognostic value of PET-CT after induction chemotherapy in patients with locally advanced nonsmall cell lung cancer (NSCLC).We analyzed 42 cases of clinical stage IIIA-N2 NSCLC who receive 2 to 4 cycles of preoperative chemotherapy with or without radiation followed by curative resection. The maximum standard uptake value (SUVmax) of the suspected lesion on PET-CT was recorded. PET-CT findings after induction chemotherapy were compared with those of initial PET-CT and pathology after surgery.The accuracy of PET-CT in restaging of the primary tumor after induction chemotherapy was 50.0%. Eighteen (42.8%) of 42 patients were underestimated ycT stage, and 3 (7.1%) of 42 patients was overestimated ycT stage by PET-CT scan. The accuracy of PET-CT in restaging of the nodal disease was 71.4%. Six (14.3%) of 42 patients were underestimated ycN stage, and 6 (14.3%) of 42 patients were overestimated ycN stage as compared with pathologic staging. The 2-year overall survival (OS) and relapse-free survival (RFS) rate were 68.5% and 40.9%, respectively. Complete responders (ycT0N0M0) on PET-CT after induction chemotherapy had a significantly longer RFS time than did incomplete responders (28.3 vs 9.1 months, P = 0.021).Complete response on PET-CT after induction chemotherapy with or without radiation was a good prognosticator for RFS in stage IIIA-N2 NSCLC patients who received surgery. However, response evaluation on PET-CT after induction chemotherapy should be interpreted with caution due to its unacceptable accuracy.

Pathological response of locally advanced rectal cancer to preoperative chemotherapy without pelvic irradiation.

Pathological response to chemotherapy without pelvic irradiation is not well defined in rectal cancer. This study aimed to evaluate the objective pathological response to preoperative chemotherapy without pelvic irradiation in middle or low locally advanced rectal cancer (LARC). Between 2008 and 2013, 22 patients with middle or low LARC (T3/4 and/or N+ and circumferential resection margin <2mm) and synchronous metastatic disease or a contraindication to pelvic irradiation underwent rectal resection after preoperative chemotherapy. The pathological response of rectal tumour was analysed according to the Rödel tumour regression grading (TRG) system. Predictive factors of objective pathological response (TRG 2-4) were analysed. All patients underwent rectal surgery after a median of six cycles of preoperative chemotherapy. Of these, 20 (91%) had sphincter saving surgery and an R0 resection. Twelve (55%) patients had an objective pathological response (TRG 2-4), including one complete response. Poor response (TRG 0-1) to chemotherapy was noted in 10 (45%) patients. In univariate analyses, none of the factors examined was found to be predictive of an objective pathological response to chemotherapy. At a median follow-up of 37.2months, none of the 22 patients experienced local recurrence. Of the 19 patients with Stage IV rectal cancer, 15 (79%) had liver surgery with curative intent. Preoperative chemotherapy without pelvic irradiation is associated with objective pathological response and adequate local control in selected patients with LARC. Further prospective controlled studies will address the question of whether it can be used as a valuable alternative to radiochemotherapy in LARC.

Resection of Borderline Resectable and Locally Advanced Pancreatic Adenocarcinomas after Neoadjuvant Chemotherapy

Objective: To report the outcomes of surgical resection of borderline resectable (BL) and locally advanced (LA) ‘unresectable' pancreatic cancer after neoadjuvant chemotherapy. Methods: A review of a prospectively maintained database for pancreatic resections was undertaken to identify patients undergoing resection for BL and LA pancreatic cancer after neoadjuvant chemotherapy between January 2007 and December 2012. Clinicopathological, surgical and survival outcomes were analyzed. Results: A total of 45 patients with LA (n = 34) or BL cancer (n = 11) underwent surgery after a mean (± SD) of 7 ± 4 preoperative chemotherapy cycles. Ninety-day mortality was 6.7%, and overall morbidity was 33.3%. An R0 resection was achieved in 34 patients, and 4 patients showed a complete pathological response. Overall median postoperative survival was 17 months (21 after the start of neoadjuvant treatment). Overall and disease-free survival was 74.9 and 43.6% at 1 year and 21.2 and 10.3% at 3 years, respectively. In BL cancer patients, the 3-year survival was significantly higher compared to that of LA cancer patients (p = 0.02). Conclusions: Curative intent resection in BL and LA cancer patients after neoadjuvant chemotherapy can be achieved with reasonable mortality and morbidity and an encouraging 3-year survival. After neoadjuvant therapy, resection provides a better overall survival for BL compared to LA cancer patients.

Could methylated reprimo cell-free DNA serve as a novel tumor marker to assess response in locally advanced gastric cancer treated with preoperative chemotherapy?

101 Background: Gastric cancer (GC) is one of the leading causes of cancer death. Perioperative chemotherapy (CT) for locally advanced GC improves curative resection rates and survival compared to surgery alone. Response assessment is challenging and no tumor markers have been validated for this purpose. We conducted a pilot study to investigate the role of methylated Reprimo (RPRM) cell-free DNA (cfDNA) as tumor marker for assessment of response to preoperative CT in patients enrolled in the study GOCCHI 2009-01 (NCT01633203). Methods: Patients with locally advanced GC referred to receive preoperative CT with Epirubicin + Cisplatin + Capecitabine for 3 cycles were offered to enter the study. Patients had to have operable GC, with baseline CT showing a transmural tumor and/or regional lymphnode metastasis with no distant spread assessed by a multidisciplinary tumor board. After the approval of the amendment of the protocol to allow blood sampling for tumor marker measurement and only if informed consent had been given, blood samples were taken at day one of each cycle of preoperative CT. The status of methylated RPRM cfDNA was assessed by Methylight and the number of copies per mL was determined. Patients with at least 2 samples were analyzed. Results: Thirteen patients signed the informed consent form for this substudy, and 11 patients had blood samples available for analysis. Of these, 8 patients had detectable methylated RPRM cfDNA on Day 1 of the first cycle (i.e. baseline). Five patients showed decrease in methylated RPRM cfDNA, while 5 patients had increased levels of the tumor marker in subsequent measurements. In one patient, methylated RPRM cfDNA was not detected in either of two assessments. One patient with a marked increase in methylated RPRM cfDNA after two cycles of CT had metastatic disease at laparotomy. Correlation between pathological findings and changes in methylated RPRM cfDNA will be presented. Conclusions: Our findings suggest that methylated RPRM cfDNA could serve as a novel tumor marker to assess response in locally advanced GC treated with preoperative chemotherapy. Further validation of these preliminary results is warranted.

Safety, efficacy, and long-term follow-up evaluation of perioperative epirubicin, Cisplatin, and capecitabine chemotherapy in esophageal resection for adenocarcinoma.

Perioperative epirubicin, cisplatin, and capecitabine (ECC) chemotherapy was evaluated in patients who underwent esophageal resection for adenocarcinoma of the esophagus or gastroesophageal junction (GEJ). A cohort of 93 consecutive patients was analyzed. The median follow-up period was 60months. Source data verification of adverse events was performed by two independent observers. All three planned preoperative chemotherapy cycles were administered to 65 patients (69.9%). Only 27% of the patients completed both pre- and postoperative chemotherapy. The reasons for not receiving postoperative adjuvant chemotherapy could be separated in two main problems: toxicity of the preoperative chemotherapy and postoperative problems involving difficulty in recovery and postoperative complications. Finally, 25 patients (27%), completed three preoperative and three postoperative cycles. Grades 3 and 4 nonhematologic adverse events of preoperative chemotherapy mainly consisted of thromboembolic events (16.2%) and cardiac complications (7.5%). A history of cardiac and vascular disease was independently associated with discontinuation of preoperative chemotherapy and the occurrence of grade 3 or higher adverse events. Surgery was performed for 94% of all the patients who started with ECC chemotherapy. A radical resection (R0) was achieved in 93% of the patients. A complete pathologic response was observed in 8% of the patients. During a median follow-up period of 60months, the median disease-free survival time was 28months, and the median overall survival time was 36months. The 3-year overall survival rate was 50%, and the 5-year overall survival rate was 42%. For patients with adenocarcinoma of the esophagus or GEJ, six cycles of ECC-based perioperative chemotherapy is associated with a relatively high number of adverse events. Although this toxicity did not affect the esophageal resectability rate, this regimen should be used with caution in this patient population.

The Efficacy and Safety of Preoperative Chemotherapy With Triweekly Abraxane and Cyclophosphamide Followed by 5-Fluorouracil, Epirubicin, and Cyclophosphamide Therapy for Resectable Breast Cancer: A Multicenter Clinical Trial

BackgroundIt has been reported that tri-weekly Abraxane therapy has better outcomes in recurrent breast cancer than tri-weekly Cremophor-based taxol therapy, and that cyclophosphamide combined with taxane shows an enhanced antitumor effect. We conducted a phase II clinical trial of preoperative chemotherapy with a combination of TRI-ABC. Patients and MethodsFrom September 2011 to September 2013, 4 cycles of preoperative chemotherapy with TRI-ABC followed by 4 cycles of FEC were administered in patients with resectable breast cancer. In patients with HER2-positive breast cancer, tri-weekly Trastuzumab was administered with TRI-ABC. The primary end point was the pathological complete response (pCR) rate in the breasts and lymph nodes. ResultsThe treatment outcomes and safety were evaluated in 54 patients who received at least 1 dose of chemotherapy. All patients underwent radical surgery, and the overall pCR rate of 37% (20 of 54) was achieved. The pCR rates according to each subtype were 8% (2 of 24) in hormone receptor (HR)-positive HER2-negative breast cancer, 56% (5 of 9) in HR-positive HER2-positive breast cancer, 63% (5 of 8) in HR-negative HER2-positive breast cancer, and 62% (8 of 13) in triple-negative breast cancer. Multivariate analysis revealed that HR negativity and HER2 positivity were predictive factors of pCR. Clinical response was observed in 49 patients (91%). The safety profile was acceptable. ConclusionPreoperative chemotherapy with TRI-ABC followed by FEC showed high efficacy and excellent safety. Further clinical studies should be conducted to compare the efficacy of TRI-ABC followed by FEC with conventional taxane–anthracycline regimens.

Prognostic significance of treatment-induced pathologic necrosis in extremity and truncal soft tissue sarcoma after neoadjuvant chemoradiotherapy.

Histologic response to chemotherapy has been shown to be an independent prognostic factor in patients with osteosarcoma and Ewing sarcoma. However, in patients with soft tissue sarcoma (STS), the prognostic impact of histologic response to chemotherapy is less clear. In the current study, the authors sought to determine the prognostic significance of treatment-induced pathologic necrosis in patients receiving neoadjuvant chemoradiotherapy for STS. Between 1989 and 2011, a total of 113 patients with grade 2 or 3 (graded according to the National Cancer Institute grading system using 3 tiers) extremity or truncal STS were identified who received neoadjuvant interdigitated chemoradiotherapy according to protocol followed by surgery. The extent of tumor necrosis in the resected specimens was quantified and correlated with outcome. The median tumor necrosis rate was 90%, and 103 patients (91%) received all 3 cycles of planned neoadjuvant chemotherapy. The likelihood of achieving ≥95% necrosis was not related to the number of preoperative cycles of chemotherapy received but was found to be related to tumor histology (62% for malignant fibrous histiocytoma vs 0% for synovial sarcoma [P<.001]; 56% for myxoid liposarcoma vs 0% for synovial sarcoma [P = .002]). At a median follow-up of 6 years, there were no statistically significant differences noted in the 5-year local control, disease-specific survival, and overall survival rates for patients with ≥95% necrosis (50 patients; 44%) and <95% necrosis (63 patients; 56%), even when stratifying by histology. In a homogeneous population of patients with high-grade extremity and truncal STS who were treated with neoadjuvant chemoradiotherapy, the extent of pathologic tumor necrosis did not correlate with outcome.

Apoptosis and KI 67 index correlate with preoperative chemotherapy efficacy and better predict the survival of gastric cancer patients with combined therapy

T he correlation of apoptotic and proliferation index with preoperative chemotherapy efficacy was investigated. Their prognostic value was also explored. 167 patients were enrolled, curative gastrectomy and D2 lymphadenectomy were performed, and a total of 12 cycles of perioperative mFOLFOX7 chemotherapy was recommended. Apoptosis index (AI) and Ki67 index (KI) in surgical specimens were detected. Apoptosis index, KI and AI/KI were significantly different between patients received perioperative chemotherapy and surgery (CS group, n = 84) and those who received only surgery and postoperative chemotherapy (S group, n = 83). In the CS group, number of patients who received 2, 4, 6 cycles of preoperative chemotherapy were, respectively, 28, 53 and 3. AI, KI and AI/KI were closely related to pathological response. Cutoff value of AI and AI/KI for response separated CS group patients into two subgroups with significant different prognosis and picked up more potential responders than pathological evaluation, especially in pathological response evaluation grade 1a–b. Apoptosis index, KI and AI/KI are significantly related to chemotherapy efficacy and prognosis of gastric cancer patients who received perioperative chemotherapy and radical gastrectomy. They could be used in combination with pathological response evaluation to distinguish more potential responders.

Randomized, multicenter, controlled evaluation of S-1 and oxaliplatin (SOX regimen) as neoadjuvant chemotherapy for advanced gastric cancer patients (RESONANCE trial).

90 Background: RESONANCE trial aims to improve 3-year disease-free survival (DFS) for patients treated with neoadjuvant chemotherapy and D2 surgery with chemotherapy postoperatively. We also evaluated the postoperative complications with and without preoperative chemotherapy to reveal the safety of SOX regimen. Methods: In this phase III multicenter study, patients with American Joint Committee on Cancer(AJCC,7thed)stage II-IIII advanced gastric cancer are treated with two to four cycles of preoperative SOX chemotherapy, followed by gastrectomy with D2 lymphadenectomy, and then another four to six postoperative cycles of SOX chemotherapy. Surgical and pathological quality control is performed. The primary endpoint is 3-year DFS, secondary endpoints are 3-year OS, D2/R0 rate, and toxicity and recurrence risk. The RESONANCE trial has been registered internationally, and twenty hospitals have participated in this trial. Results: Between February 2012 and to August 2013, 128 patients were enrolled in the neoadjuvant group , 103 patients were enrolled in the adjuvant group. Seventy-four of 128 patients underwent gastrectomy with D2 lymphadenectomy after preoperative chemotherapy. In these 74 patients, 52 (70%) patients had clinical tumor response and 10 (14%) patients achieved histological response. Operative mortality was never encountered. R0 resection rate was 90.5% after neoadjuvant chemotherapy compared with 94.2% in adjuvant group (p=0.23). Postoperative complication rates in neoadjuvant and adjuvant groups were 33.8% and 37.9% respectively (p=0.58). Conclusions: Results of this study will demonstrate whether neoadjuvant chemotherapy strategy will be superior to adjuvant chemotherapy when combined with D2 surgery for AJCC stage II-III gastric cancer patients. Furthermore, it might be an important clinical evidence to verify benefit of neoadjuvant chemotherapy in advanced gastric cancer. Clinical trial information: NCT01583361.

Is [F-18]-fluorodeoxy-D-glucose positron emission tomography of value in the management of patients with craniofacial bone sarcomas undergoing neo-adjuvant treatment?

BackgroundWe evaluated the role of 18FDG PET/CT used to assess response to preoperative chemotherapy in patients with primary craniofacial bone sarcomas.MethodsFourteen patients with craniofacial bone sarcomas (13 osteosarcoma, 1 spindle cell sarcoma) were retrospectively evaluated. All patients received up to 6 cycles of preoperative chemotherapy followed by resection of the primary tumour. Response to treatment was assessed using MRI (RECIST criteria) and 18FDG PET/CT (EORTC guidelines), performed at least at baseline, after 2-4 cycles and pre-operatively.ResultsThe median baseline 18FDG PET/CT SUV was 10.2 (range 0-41); in 2 patients no uptake was detected. The preoperative 18FDG PET/CT, compared with the baseline, demonstrated a partial metabolic response in 7 patients (59%), complete metabolic response in 2 (16%) and stable metabolic disease in 3 (25%). In contrast, only two patients achieved a RECIST response on MRI: 10 (83%) had stable disease. One patient underwent early resection due to clinical progression after an initial response to treatment. This was confirmed by PET (SUV from 21 to 42) but not on MRI. Twelve of 14 patients (86%) had <90% histological necrosis in the resected tumour. At a median follow-up 23 months, 11 patients (79%) remain disease free, two had metastatic progression (14%) and 1 a local relapse (7%). The median DFS was 17 months. For those patients who achieved a response to preoperative 18FDG PET/CT the median DFS was 19 months (range: 1-66) compared with 3 months (range: 3-13) in those who did not (p = 0.01). In contrast, the median disease free survival (DFS) did not differ according to histological response (19 versus 17 months, >90% versus <90% necrosis, p = 0.45) or resection margins (19 months for R0 versus 18 months for R1, p = 0.2).Conclusion18FDG PET/CT is more reliable than standard imaging in evaluating response to neo-adjuvant chemotherapy in craniofacial bone sarcomas, changed management in one patient, and in this small series, correlated better with patient outcome than histological response and resection margins. These results warrant prospective validation in a larger cohort of patients.

Preoperative Chemotherapy Plus Bevacizumab and Morbidity after Resection of Colorectal Cancer Liver Metastases

Aims and background: The addition of bevacizumab to preoperative chemotherapy is a common therapeutic practice in patients with colorectal liver metastases. The aim of the present study was to assess the effect of bevacizumab on postoperative complications after liver resection. Methods:A retrospective analysis was performed including patients who underwent liver resection for colorectal liver metastases after receiving chemotherapy with or without bevacizumab in two hospitals. Univariate logistic regression models were used to identify predictors of postoperative morbidity in both groups of patients. Results: A total of 76 patients were analyzed: 22 patients did not receive preoperative chemotherapy (control group), 21 patients received preoperative chemotherapy alone and 33 patients received preoperative chemotherapy in combination with bevacizumab. The median number of chemotherapy cycles received was 4 (range, 1-23) for the chemotherapy group and 7 (range, 2-36) for the chemotherapy plus bevacizumab group Morbidity rate was similar in the three groups of patients considered: 54.5 %, 47.6% and 39.4, respectively. The most common complications were infections and wound complications. The number of preoperative chemotherapy cycles received was the only clinical variable that was significantly correlated with postoperative comorbidity. Conclusions: Our results support the evidence that the addition of bevacizumab to preoperative chemotherapy does not increase the risk of complications following surgery of colorectal liver metastases.

Ruptured hepatoblastoma: A case report and literature review

The spontaneous rupture of hepatoblastoma in childhood is a rare life-threatening event. Despite never being firmly documented this event is considered to play a negative impact on long term survival. Herewith the clinical history of a 6-month-old child with a very large mass and intratumoral bleeding at the diagnosis, who suffered of spontaneous tumor rupture after two cycles of pre-operative chemotherapy and ultimately died of tumor recurrence despite appropriate treatment, is reported. In addition to this case the pertinent literature regarding the prognostic implication of tumor rupture in childhood hepatoblastoma (at the time of diagnosis or during treatment) is reviewed. This report is meant to focus the problem of the clinical and prognostic relevance of tumor rupture and to stimulate appropriate large scale studies aimed to investigate the prognostic value of this event, and to identify the clinical tumor characteristics which may predict its occurrence.

A randomised trial comparing preoperative to perioperative chemotherapy in early-stage non-small-cell lung cancer (IFCT 0002 trial)

HypothesisThere will be a detectable increase in overall survival (OS) using preoperative (PRE) as opposed to perioperative (PERI) chemotherapy in resectable StageI–II non-small-cell lung cancer (NSCLC). MethodsThis multicenter, open-label, randomised trial with a 2×2 factorial design first compared two chemotherapy strategies (PRE versus PERI), then two chemotherapy regimens (gemcitabine–cisplatin [GP] versus paclitaxel–carboplatin [TC]). The PRE group received two preoperative cycles followed by two additional preoperative cycles, while the PERI group underwent two preoperative cycles followed by two postoperative cycles, the 3rd and 4th cycles being given only to responders in both cases. ResultsA total of 528 patients were randomised, 267 of which were assigned to the PRE group and 261 to the PERI group. Three-year OS did not differ between the two groups (67.4% and 67.7%, respectively; hazard ratio (HR)=1.01 [0.79–1.30], p=0.92), nor did 3-year disease-free survival, response rates, toxicity, or postoperative mortality. Pathological complete response was observed in 22 (8.2%) and 16 patients (6.1%), respectively. Although quality of life did not differ significantly, chemotherapy compliance was significantly higher in the PRE group. The proportion of responders who received Cycles 3 and 4 was significantly higher in the PRE group (90.4% versus 75.2%, p=0.001). In responders, the dose intensity of Cycles 3 and 4 was higher in the PRE group than in the PERI group (mean relative dose intensity of 90.4% versus 82.6%, respectively; p=0.0007). There was no difference between GP and TC in 3-year OS (HR=0.97 [95% confidence interval (CI): 0.76–1.25], p=0.80) or response rates. However, the regimens’ toxicity profiles differed. ConclusionsThis study failed to demonstrate any difference in survival between patients receiving preoperative and perioperative chemotherapy in early-stage NSCLC. The increase from two to four preoperative chemotherapy cycles did not increase the pathological response rate.

Pathologic complete response (pCR) with weekly nanoparticle albumin bound (nab-P) plus carboplatin (C) followed by doxorubicin plus cyclophosphamide (AC) with concurrent bevacizumab (B) for triple-negative breast cancer (TNBC).

1068 Background: TNBC are mostly “basal-like” tumors, that have been shown to overexpress Secreted Protein Acidic and Rich in Cysteine (SPARC). Endothelial transcytosis of nab-P via albumin- gp60 -cav1 and binding of albumin to SPARC results in high intratumoral levels of nab-P. Exploiting this and the dysfunctional DNA repair in basal tumors, we hypothesized that nab-P + C would produce high rates of pCR in TNBC, further enhanced by antiangiogenesis properties of B. Methods: Eligible women had operable TNBC ≥ 2 cm. pCR in the breast and pCR in the breast + nodes were primary &amp; secondary end points respectively. We needed 57 evaluable patients to demonstrate 40% pCR vs. 25% (P0) in a single stage phase II design (α: 0.05, β: 0.2).Schema: C AUC 6 d1 + nab-P 100mg/m2d 1, 8 &amp; 15 Q 28 d x 4 cycles followed by AC d1, Q14d x 4 cycles preoperatively with B 10mg/kg Q 14d for the first 6 cycles of preoperative chemotherapy, resuming postoperatively to complete 1 year of treatment.Baseline tumor biopsies &amp; serial serum/blood samples were collected. Results: Due to slow accrual, study was closed after 42 patients. They were women between 35 and 68 years of age (median 52); 51% were African American and 46% were node positive. Safety population: N=41. Four patients came off study prior to surgery while 7 are still on pre-op treatment. Grade ¾ hematologic AEs: neutropenia (Gr3: 56%; Gr4:24%) febrile neutropenia (4%), thrombocytopenia (32%), anemia (22%). 7 patients had SAEs, with 1 grade 5 event. To date, thirty of 31 patients who had surgery (efficacy population) are considered evaluable per protocol. In-breast pCR rates are 55% (17/31) and 56% (17/30) and the rates of pCR breast + nodes are 52% (16/31) and 53% (16/30), for the efficacy and evaluable populations respectively. Conclusions: Majority of the patients in our study achieved a pCR, which is among the highest rates reported compared to anthracyclines+ taxanes without B in TNBC. Correlative analyses are planned. An ongoing randomized intergroup study is evaluating the individual contributions of carboplatin &amp; bevacizumab to pCR in TNBC. Clinical trial information: NCT00777673.