Survival Benefit Of Neoadjuvant Chemotherapy Research Articles

Implementation of neoadjuvant chemotherapy in muscle invasive bladder cancer treatment in Poland: a single institution retrospective study.

IntroductionEven though the survival benefit of neoadjuvant chemotherapy (NAC) in the treatment of muscle invasive bladder cancer (MIBC) is well established, NAC has not been widely used in Poland until recently. The aim of our study was to evaluate the utilization of NAC and its association with survival in MIBC.Material and methodsPatients who underwent radical cystectomy (RC) for MIBC between December 2012 and December 2017 were included in the study. Data were collected in the perioperative period and long-term observation was continued up to August 2018. Kaplan-Meier curves were used to estimate the probability of survival.ResultsA sample of 155 patients with a median age of 65 (IQR: 60–69) years was analyzed. In this group, 79 patients (51%) were treated with NAC prior to RC. Patients in the NAC+RC group were younger, more often had a positive smoking history, and had lower preoperative levels of hemoglobin, white blood cells and C-reactive protein. A 90-day complication rate and mortality were similar in both groups and in the entire cohort were equal to 64.5% and 5.2%, respectively. The overall survival (OS) was on average 150 days longer in the RC+NAC group compared to the RC-only group when patients were followed-up for 3 years (95%CI:3 4 – 267; p = 0.011).ConclusionsWe demonstrated a high utilization of NAC at our institution. The use of NAC was associated with a better prognosis than RC alone and was not associated with an increased morbidity or mortality. Our results support the use NAC as a safe and effective treatment modality in MIBC.

Does neoadjuvant chemotherapy affect postoperative complication rates in elderly patients treated with radical cystectomy for bladder cancer?

e16526 Background: Although the survival benefit of neoadjuvant chemotherapy (NAC) in bladder cancer patients receiving radical cystectomy (RC) has been established, the NAC associated complication rate is not well-known, especially in elderly patients. Methods: We identified 427 patients who had undergone RC for clinical TanyN0M0 bladder cancer from 2005 to 2015 at our 7 institutions. Among them, 118 (27.6%) were treated with gemcitabine and cisplatin (GC)-NAC. The details of the complication rate during and after RC were recorded according to the Clavien-Dindo classification. We evaluated the association between the complication rate for RC with NAC and patient age. Results: Overall, 60 (14.0%), 306 (71.7%), and 61 (14.3%) patients were < 60, 60-79, and ≥ 80 years old, respectively. Overall, 190 (44.5%) patients had some kind of postoperative complication and there was no difference in the postoperative complication rate between the NAC and non-NAC groups (37.3% vs 47.2%: p = 0.065). However, the incidence rate of post-operative ileus in the NAC group was 9.3%, which was significantly lower than that in the non-NAC group (19.1%, p = 0.013). Sixteen (26.7%), 93 (30.4%) and 9 (14.8%) patients in the < 60, 60-79, and ≥ 80 age groups, respectively, received GC-NAC. Among patients < 60 years old, the complication rates for post-operative ileus, pyelonephritis and wound infection were 12.5%, 18.8%, and 0% in the NAC group, which were not significantly different from those in the non-NAC group (9.1%, 6.8%, and 13.6%, respectively). Among 60-79 year-old patients, the corresponding complication rates were 8.6%, 11.8%, and 9.7% in the NAC group, which were not significantly different from those in the non-NAC group (17.8%, 9.9%, and 9.4%, respectively). Among patients ≥ 80 years old, the rates were 11.1%, 11.1%, and 33.3% in the NAC group, which were not significantly different from those in the non-NAC group (28.8%, 11.5%, and 13.5%, respectively). Furthermore, in patients treated with GC-NAC, no association was observed in the complication rates among patients < 60 years, 60-79 years, and ≥ 80 years old. Conclusions: NAC could be provided safely at the time of RC regardless of patient age.

Neoadjuvant chemotherapy for gastric cancer. Is it a must or a fake?

AIMTo investigate the neoadjuvant chemotherapy (NAC) effect on the survival of patients with proper stomach cancer submitted to D2 gastrectomy.METHODSWe proceeded to a review of the literature with PubMed, Embase, ASCO and ESMO meeting abstracts as well as computerized use of the Cochrane Library for randomized controlled trials (RCTs) comparing NAC followed by surgery (NAC + S) with surgery alone (SA) for gastric cancer (GC). The primary outcome was the overall survival rate. Secondary outcomes were the site of the primary tumor, extension of node dissection according to Japanese Gastric Cancer Association (JGCA) performed in both arms, disease-specific (DSS) and disease-free survival (DFS) rates, clinical and pathological response rates and resectability rates after perioperative treatment.RESULTSWe identified a total of 16 randomized controlled trials comparing NAC + S (n = 1089) with SA (n = 973) published in the period from January 1993 - March 2017. Only 6 of these studies were well-designed, structured trials in which the type of lymph node (LN) dissection performed or at least suggested in the trial protocol was reported. Two out of three of the RCTs with D2 lymphadenectomy performed in almost all cases failed to show survival benefit in the NAC arm. In the third RCT, the survival rate was not even reported, and the primary end points were the clinical outcomes of surgery with and without NAC. In the remaining three RCTs, D2 lymph node dissection was performed in less than 50% of cases or only recommended in the “Study Treatment” protocol without any description in the results of the procedure really perfomed. In one of the two studies, the benefit of NAC was evident only for esophagogastric junction (EGJ) cancers. In the second study, there was no overall survival benefit of NAC. In the last trial, which documented a survival benefit for the NAC arm, the chemotherapy effect was mostly evident for EGJ cancer, and more than one-fourth of patients did not have a proper stomach cancer. Additionally, several patients did not receive resectional surgery. Furthermore, the survival rates of international reference centers that provide adequate surgery for homogeneous stomach cancer patients’ populations are even higher than the survival rates reported after NAC followed by incomplete surgery.CONCLUSIONNAC for GC has been rapidly introduced in international western guidelines without an evidence-based medicine-related demonstration of its efficacy for a homogeneous population of patients with only stomach tumors submitted to adequate surgery following JGCA guidelines with extended (D2) LN dissection. Additional larger sample-size multicentre RCTs comparing the newer NAC regimens including molecular therapies followed by adequate extended surgery with surgery alone are needed.

The survival benefit of neoadjuvant chemotherapy and pCR among patients with advanced stage triple negative breast cancer.

Triple negative breast cancer (TNBC) is an aggressive subtype that accounts for 15-20% of cases, with a higher incidence of relapse/death. Even with adjuvant chemotherapy, the 5 year distant metastasis-free survival rate remains low. A total of 452 tumor registry patients with TNBC and no evidence of metastatic disease were identified over the period of 1996-2011. The median age and follow-up time were 51 (range=21-88) and 3.9 (range=0.14-14) years. Approximately 75% of patients with stage III disease received neoadjuvant chemotherapy (NACT) compared with 47% for stage II. Patients with stage I disease predominantly received adjuvant chemotherapy (ACT). Among those who underwent NACT (n=202), 33% had a pathological complete response (pCR). Overall (OS) and disease-free (DFS) survival were significantly longer among patients achieving pCR (versus residual disease) following NACT (OS: all patients P<0.0001, stage II P<0.0001, stage III P=0.0062; DFS: all patients P<0.0001, stage II P=0.0011, stage III P=0.015). ACT was not associated with improved OS or DFS for stage III disease. Adjustment for age, chemotherapy, health insurance type, lymphovascular invasion, race, radiation, and surgery did not alter our results. These findings suggest that pCR following NACT is associated with improved survival among patients with TNBC, independent of diagnostic stage.

Effect of older age and comorbitities on outcomes with neoadjuvant chemotherapy (NAC) for epithelial ovarian cancer (EOC).

e17101 Background: Although a survival benefit for NAC has not been shown in the overall population of EOC, some patients may benefit from NAC. This analysis evaluates the role of age and comorbidities on the effect of NAC compared to upfront surgery on survival among EOC patients in New York. Methods: Patients who underwent surgery for stage II-IV EOC from 2006-2013 were included from the New York State Cancer Registry and the Statewide Planning and Research Cooperative System. Elderly age was defined as &gt;70 years. Comorbidity burden was defined with the Charlson Comorbidity Index (CCI). Cox models were used to examine the effect of NAC on 5 year overall survival. The analysis was then stratified by age and comorbidity score to evaluate the role of NAC in specific subgroups. Results: 4617 patients met inclusion criteria of which 25% were elderly and 11% received NAC. Factors associated with receipt of NAC included age &gt; 70, advanced stage, serous histology and high hospital volume (p&lt;0.01). After adjustment for patient, hospital, and surgeon characteristics, NAC was associated with a 27% (p&lt;0.01) increase in 5 year overall mortality in all EOC patients. Among the elderly, NAC did not have a significant effect on overall (p=0.47) or EOC-specific survival (p=0.24). Elderly and non-elderly women without comorbidities had a higher risk of death with NAC than primary surgery. There was a trend towards improved survival among elderly patients with higher comorbidity scores. (Table) Conclusions: The impact of NAC on EOC survival differs dependent on age and comorbidities. Patients with no comorbidities may have better prognosis with upfront surgery. Counterintuitively, those with more comorbidities, particularly the elderly, may derive survival benefit from upfront neoadjuvant therapy. [Table: see text]

177 - Survival benefit of neoadjuvant chemotherapy for muscle invasive bladder cancer in elderly patients

177 - Survival benefit of neoadjuvant chemotherapy for muscle invasive bladder cancer in elderly patients

A phase III, multicenter randomized controlled trial of neo-adjuvant chemotherapy paclitaxel plus cisplatin versus surgery alone for stage IIA-IIIB esophageal squamous cell carcinoma.

The survival benefits of neoadjuvant chemotherapy (NAC) for esophagus squamous cell carcinoma (ESCC) remains controversial. The surgical procedure was not well defined in NAC strategy, in past trials. The different surgical procedure and different levels of lymphadenectomy may decrease the survival benefits from NAC. The new chemotherapy regimen with paclitaxel is promising. The purpose of this study is to confirm the superiority of paclitaxel, cisplatin and McKeown esophagectomy with total two-field lymphadenectomy compared with surgery alone for ESCC. A two-arm phase III trial was launched in June 2015. A total of 528 patients will be recruited from eight Chinese institutions within 2.5 years. The overall survival (OS) is the primary endpoint, and the secondary endpoints include disease-free survival (DFS), R0 resection rate, complication rate, perioperation mortality, days of hospitalization, quality of life (QOL), NAC response rate, pathologic response rate, toxicities of NAC, prognostic factors, predictive factors, progression-free survival (PFS), and adverse events. The study will provide the final conclusion of NAC for ESCC in China. NCT02442440 (https://register.clinicaltrials.gov/).

Pathological complete response after neoadjuvant chemotherapy for rectal cancer with synchronous multiple liver metastases: a report of an unusual case.

BackgroundSystemic chemotherapy for stage IV colorectal cancer has advanced markedly in the recent years. We report an unusual case of 13 synchronous liver metastases for which a pathological complete response was achieved with neoadjuvant chemotherapy (NAC) consisting of a combination of 5-fluorouracil (5-FU), oxaliplatin, leucovorin (mFOLFOX6), and bevacizumab.Case presentationA 44-year-old man was diagnosed with colorectal cancer with synchronous liver metastases. We resected the primary rectal tumor first. Further, after providing NAC for hepatic metastases, lateral segmentectomy and partial resection of the liver were performed. The subsequent result was compatible with a complete pathological response. The postoperative course was uneventful, and the patient is currently alive 5 years after the first surgery without evidence of recurrence and without adjuvant chemotherapy.ConclusionsFor patients with initially resectable colorectal liver metastases, the survival benefits of NAC are still unclear. We report a rare case of 13 synchronous liver metastatic lesions from rectal cancer with a complete pathological response after neoadjuvant bevacizumab-containing chemotherapy.

Response and survival of breast cancer intrinsic subtypes following multi-agent neoadjuvant chemotherapy.

BackgroundPredicting treatment benefit and/or outcome before any therapeutic intervention has taken place would be clinically very useful. Herein, we evaluate the ability of the intrinsic subtypes and the risk of relapse score at diagnosis to predict survival and response following neoadjuvant chemotherapy. In addition, we evaluated the ability of the Claudin-low and 7-TNBCtype classifications to predict response within triple-negative breast cancer (TNBC).MethodsGene expression and clinical-pathological data were evaluated in a combined dataset of 957 breast cancer patients, including 350 with TNBC, treated with sequential anthracycline and anti-microtubule-based neoadjuvant regimens. Intrinsic subtype, risk of relapse score based on subtype and proliferation (ROR-P), the Claudin-low subtype and the 7-TNBCtype subtype classification were evaluated. Logistic regression models for pathological complete response (pCR) and Cox models for distant relapse-free survival (DRFS) were used.ResultsBasal-like, Luminal A, Luminal B, and HER2-enriched subtypes represented 32.7 %, 30.6 %, 18.2 %, and 10.3 % of cases, respectively. Intrinsic subtype was independently associated with pCR in all patients, in hormone receptor-positive/HER2-negative disease, in HER2-positive disease, and in TNBC. The pCR rate of Basal-like disease was >35 % across all clinical cohorts. Neither the Claudin-low nor the 7-TNBCtype subtype classifications predicted pCR within TNBCs after accounting for intrinsic subtype. Finally, intrinsic subtype and ROR-P provided independent prognostic information beyond clinicopathological variables and type of pathological response. A 5-year DRFS of 97.5 % (92.8–100.0 %) was observed in these neoadjuvant-treated and clinically node-negative patients predicted to be low risk by ROR-P (i.e. 57.4 % of Luminal A tumors with clinically node-negative disease).ConclusionsIntrinsic subtyping at diagnosis provides prognostic and predictive information for patients receiving neoadjuvant chemotherapy. Although we could not exclude a survival benefit of neoadjuvant chemotherapy in patients with early breast cancer with clinically node-negative and ROR-low disease at diagnosis, the absolute benefit of cytotoxic therapy in this group might be rather small (if any).Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-015-0540-z) contains supplementary material, which is available to authorized users.

Reevaluation of Neoadjuvant Chemotherapy for Esophageal Squamous Cell Carcinoma: A Meta-Analysis of Randomized Controlled Trials Over the Past 20 Years.

The effect of neoadjuvant chemotherapy on the survival of patients with thoracic esophageal squamous cell carcinomas (ESCCs) remains controversial. The optimal management strategy for resectable ESCCs varies regionally based on local randomized controlled trials. A systematic review and meta-analysis was conducted to re-evaluate this controversial issue.A systematic review of the Medline, Embase, and PubMed databases was carried out on data collected between August 1994 and August 2014 to evaluate the role of neoadjuvant chemotherapy. Only randomized controlled trials comparing the effects of neoadjuvant chemotherapy with that of surgery and surgery plus adjuvant chemotherapy were selected.Six studies with a total of 1202 patients were identified, consisting of a neoadjuvant chemotherapy arm (n = 597) and a surgery alone and surgery plus adjuvant chemotherapy arm (n = 605). The 5-year overall survival benefit for neoadjuvant chemotherapy was statistically significant at α = 0.1 (hazard ratio = 0.81, 95% confidence intervals, 0.65–1.00, P = 0.053). All 6 trials recruited patients for more than 5 years with undefined lymphadenectomies. Cisplatin and fluorouracil were adopted as neoadjuvant chemotherapy regimens.The role of neoadjuvant chemotherapy for ESCC is worth re-investigating. The design of randomized controlled trials should adopt new chemotherapy regimens as well as define the surgical procedure and the details of the lymphadenectomy.

Survival benefit of neoadjuvant chemotherapy for resectable cancer of the gastric and gastroesophageal junction: a meta-analysis.

The objective of the present meta-analysis was to estimate the magnitude of survival benefits of neoadjuvant chemotherapy (NAT) in resectable cancer of the gastric and gastroesophageal junction. We searched PubMed, Embase, the Cochrane Library, ISI Web of Knowledge, Chinese biomedical literature database, Chinese Scientific Journals full-text database of retrieved articles from their inception to 2013. Two reviewers independently retrieved study and data extraction of included studies. Results regarding the overall survival and progression-free survival in the meta-analysis were expressed as hazard ratios (HRs) with 95% confidence intervals (CI). Twelve randomized control trials (n=1755) were eligible for final meta-analysis. NAT was associated with a statistically significant benefit in terms of overall survival (HR=0.72; 95% CI, 0.56-0.93, P=0.01), progression-free survival (HR=0.73; 95% CI, 0.62-0.87, P=0.0003), 5-year survival rate [relative risk (RR)=1.36; 95% CI, 1.10-1.67, P=0.0004], and curative resection rate (RR=1.11; 95% CI, 1.03-1.20, P=0.009). Five-year survival rate increased from 30% to 42% with NAT. No significant difference with regards to overall postoperative complications rate (RR=1.08; 95% CI, 0.92-1.27, P=0.28) was found between 2 groups. There is convincing evidence for a survival benefit of NAT over surgery alone in patient with cancer of the gastric and gastroesophageal junction.

Neoadjuvant Chemotherapy for Clinical Stage II and III Thoracic Esophageal Squamous Cell Carcinoma with Curative Esophagectomy

Esophageal squamous cell carcinoma (ESCC) is a gastrointestinal carcinoma with a poor prognosis. To improve the survival of patients with this disease, neoadjuvant chemotherapy (NAC) has been introduced. However, the survival benefits of NAC or the correlation between NAC and postoperative complications have not been well considered. In the present study, we retrospectively investigated the clinicopathological effectiveness of NAC in patients with clinical stage II and III thoracic ESCC. This retrospective study enrolled 63 patients with clinical stage II and III thoracic ESCC, who underwent resection of the thoracic esophagus and three-field lymph node dissection between January 2007 and December 2013. NAC with cisplatin plus 5-fluorouracil (5-FU) was introduced in 38 patients. NAC did not correlate with the occurrence of postoperative complications. The 5-year disease-free survival (DFS) rate of the 38 patients with NAC (41.6%) was similar to that for the 25 patients who did not receive NAC (38.1%; P = 0.784). However, we found that the DFS of 17 patients with histopathological Grade 2 and 3 tumors who received NAC (5-year DFS rate: 58.1%) was significantly higher than that of 21 patients with low histopathological grade tumors who received NAC (5-year DFS rate: 28.6%), or than that of the 25 patients who did not receive NAC (38.1%). Moreover, we found that the effectiveness of NAC assessed macroscopically did not correlate with the effectiveness of NAC assessed microscopically. These findings may indicate that preoperative estimation of NAC effectiveness is important in avoiding unnecessary adverse drug effects caused by NAC, and in prolonging the survival of patients with thoracic ESCC. * Corresponding author.

Meta-analysis of postoperative morbidity and perioperative mortality in patients receiving neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal and gastro-oesophageal junctional cancers

The long-term survival benefits of neoadjuvant chemotherapy (NAC) and chemoradiotherapy (NACR) for oesophageal carcinoma are well established. Both are burdened, however, by toxicity that could contribute to perioperative morbidity and mortality. MEDLINE, the Cochrane Library and Embase were searched to capture the incidence of any postoperative complications, cardiac complications, respiratory complications, anastomotic leakage, postoperative 30-day mortality, total postoperative mortality and treatment-related mortality in randomized clinical trials comparing NAC or NACR with surgery alone, or NAC versus NACR. Meta-analyses comparing NAC and NACR were conducted by using adjusted indirect comparison. Twenty-three relevant studies were identified. Comparing NAC or NACR with surgery alone, there was no increase in morbidity or mortality attributable to neoadjuvant therapy. Subgroup analysis of NACR for squamous cell carcinoma (SCC) suggested an increased risk of total postoperative mortality and treatment-related mortality compared with surgery alone: risk ratio 1·95 (95 per cent confidence interval 1·06 to 3·60; P = 0·032) and 1·97 (1·07 to 3·64; P = 0·030) respectively. A combination of direct comparison and adjusted indirect comparison showed no difference between NACR and NAC regarding morbidity or mortality. Neither NAC nor NACR for oesophageal carcinoma increases the risk of postoperative morbidity or perioperative mortality compared with surgery alone. There was no clear difference between NAC and NACR. Care should be taken with NACR in oesophageal SCC, where an increased risk of postoperative mortality and treatment-related mortality was apparent.

Accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC) as neoadjuvant chemotherapy for patients with muscle‐invasive transitional cell carcinoma of the bladder

Meta-analysis data demonstrate a 5% absolute survival benefit for neoadjuvant chemotherapy (NAC) using cisplatin-based combination regimens in the radical treatment of muscle-invasive bladder cancer (MIBC). However, there are no randomized, controlled trial data on the optimum regimen. Accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC) is a dose-intense regimen that has the potential to minimize delays to definitive, potentially curative therapy. A retrospective analysis is presented of the efficacy and toxicity of AMVAC as NAC in patients with MIBC and its impact on the patient pathway. Eighty consecutive patients with MIBC were treated with AMVAC as NAC by 2 UK multidisciplinary uro-oncology teams. Three or 4 cycles of AMVAC (methotrexate 30 mg/m(2) , vinblastine 3 mg/m(2) , doxorubicin 30 mg/m(2) , and cisplatin 70 mg/m(2) ) were given at 2-week intervals, with granulocyte colony-stimulating factor support, prior to either radical surgery or radical radiotherapy. All planned cycles of chemotherapy were completed, without dose reduction or delay in 84% of patients. All 80 patients subsequently received their planned definitive therapy. Grade 3/4 toxicities were seen in 26% of the 42% of patients for whom toxicity data are available, including 12% grade 3/4 neutropenia. Pathological complete response to AMVAC was seen in 43% of 60 surgical patients. Objective radiological local response was seen in 83% of 57 evaluable patients. Two-year disease-free and overall survival were 65% and 77%, respectively. AMVAC is safe and appears to be a well-tolerated and effective NAC regimen for MIBC. It minimizes delays to definitive treatment and produces excellent pathological and radiological response rates. It is an appropriate comparator for future randomized trials.

Interaction between preoperative CA-125 level and survival benefit of neoadjuvant chemotherapy in advanced epithelial ovarian cancer

Objective This study aims to determine whether neoadjuvant chemotherapy (NAC) has survival benefit in selected patients with advanced epithelial ovarian cancer (EOC) who have high risk of suboptimal cytoreduction which is represented by high serum CA-125 level. Methods We retrospectively reviewed records of 314 patients with EOC including 94 patients who received NAC. After stratification by preoperative CA-125 levels, the progression-free survival (PFS) was compared between the NAC group and the primary debulking surgery (PDS) group. Results The NAC group had more FIGO stage IV disease ( P < 0.001) and higher CA-125 levels ( P < 0.001). Although suboptimal resection rate was higher in the PDS group (50% vs. 18%, P < 0.001), however, NAC was not associated with increased PFS in multivariate Cox analysis ( P = 0.334). Nevertheless, after stratification according to CA-125 levels, NAC showed survival benefit in the subgroup with high CA-125 levels (> 2000 U/ml; HR 0.62, P = 0.037). Conclusion Our preliminary data suggests the possible interaction between CA-125 levels and survival benefit of NAC. The randomized trial data about NAC should be stratified by the reproducible and relevant criteria such as preoperative serum CA-125 level to elucidate true survival benefit of NAC in ovarian cancer.

Survival Benefit of Neoadjuvant Chemotherapy in Non-small Cell Lung Cancer: An Updated Meta-Analysis of 13 Randomized Control Trials

The survival effectiveness of neoadjuvant chemotherapy in non-small cell lung cancer (NSCLC) is still unclear based on the study of most up-to-date literatures. This article contributes to this problem by conducting an updated meta-analysis. Based on Burdett et al's (J Thorac Oncol 2006;1:611-621) systematic review, this meta-analysis was conducted. Articles were searched electrically. The possible survival benefit of neoadjuvant chemotherapy was assessed by hazard ratio (HR) in terms of overall survival. A subgroup meta-analysis with only stage III NSCLC was also conducted. The software of Review Manager was used for data management. Thirteen randomized control trials, 6 of which were new ones, were included into this meta-analysis. The overall survival of NSCLC patients in neoadjuvant chemotherapy arm were improved significantly, comparing with those in surgery-alone arm (combined HR = 0.84; 95% confidence interval, 0.77-0.92; p = 0.0001). When only patients with stage III NSCLC were considered, the result was similar (combined HR = 0.84; 95% confidence interval, 0.75-0.95; p = 0.005). Neoadjuvant chemotherapy, as an addition of surgery, would significantly improve the overall survival of operable NSCLC patients, including patients with stage III NSCLC.

Overall Survival with Cisplatin and 5-Fluorouracil Neoadjuvant Treatment in Patients with Esophageal Cancer: Single-Center Experience

Background: The survival benefit of neoadjuvant chemotherapy in patients undergoing surgery for esophageal cancer is unclear. Patients and Methods: We retrospectively identified 37 patients with resectable esophageal squamous cell carcinoma or adenocarcinoma, who prior to surgery received 2 cycles of chemotherapy, consisting of cisplatin 80 mg/m² as 3-h intravenous infusion on day 1 followed by 5-fluorouracil 1,000 mg/m² as 96-h continuous infusion on days 1–4, separated by a 3-week interval. Surgery was performed 3–5 weeks after the start of the second cycle of chemotherapy. Results: The overall response rate was 30% (all partial responses). All patients underwent surgery, 32 with esophagectomy (29 transhiatal, 3 transthoracic). Median overall survival (OS) in all patients was 23 months, and was longer in responding than in non-responding patients (32 vs. 19 months). 5 patients with locally unresected tumor and 18 patients with microscopic surgical margin involvement (R1) underwent postoperative chemoradiotherapy or radiotherapy. Median OS in patients after radical tumor resection (R0) was comparable with that in patients who underwent R1 resection (25 vs. 23 months). Conclusions: This retrospective analysis suggests that neoadjuvant chemotherapy prolongs survival in patients with esophageal cancer who responded to chemotherapy compared with non-responding patients.

Efficacy of different types of treatment in FIGO stage IB2 cervical cancer in Korea: results of a multicenter retrospective Korean study (KGOG-1005)

The purpose of this study is to review FIGO stage IB2 cervical cancers in Korea for the past 10 years, and evaluate the most frequently employed and appropriate management strategy, and also assess the survival benefits of neoadjuvant chemotherapy (NAC). This is a retrospective chart review of 727 FIGO stage IB2 patients from 1995 to 2005. Six hundred ninety-two patients were enrolled, and all dates on which the patients died were double checked through the "National Registry of Death Statistics" of the Korea National Statistical Office. Management strategies were divided into five groups according to the primary treatment modality. The most frequently employed primary treatment modality for stage IB2 cervical cancer in Korea during the past 10 years was radical hysterectomy (RH). The next was NAC, followed by radiotherapy (RT) and/or extrafascial hysterectomy, concurrent chemoradiotherapy (CCRT) and/or extrafascial hysterectomy, in descending order. The surgery group showed the best results, with an 89% 5-year disease-free survival rate. However, there was no statistical difference between the surgery, NAC, and CCRT groups. For FIGO stage IB2 cervical cancer during the past 10 years in Korea, RH and adjuvant RT or CCRT was the most frequently employed treatment strategy. As a primary modality, RH, NAC, and CCRT showed similar survival rates. However, RH demonstrated the best survival rate among the above treatment strategies.

Neoadjuvant S-1 and cisplatin for gastric carcinoma: there will be more to come

of nodal dissection performed for this predominantly node-positive population, while no detailed data regarding the extent of surgery are offered in the other study, which also was performed for node-positive gastric cancer. On the other hand, in a subset with a relatively high survival rate, an adjuvant therapy may have very little to add to what has been already achieved by surgery. Investigators were astonished and disappointed to find in a Japan Clinical Oncology Group (JCOG) 9206-2 study that an intensive treatment consisting of intraperitoneal cisplatin (CDDP) and postoperative intravenous 5-fluorouracil/CDDP followed by oral UFT given for 12 months against serosa-positive cancer had absolutely no impact on survival [3]. Lack of impact of intraperitoneal CDDP, in addition to poor compliance (less than 40% of patients tolerated the planned treatment), has been considered at least partially responsible for this result. A more active and aggressive approach could be tolerated only if given prior to surgery, and JCOG investigators are currently more enthusiastic about exploring the benefits of neoadjuvant chemotherapy. A current treatment regimen extensively tested by JCOG in this setting is a combination of CDDP and oral S-1, which has been acclaimed for achieving a response rate above 70% in a phase II trial [4], and it is the experience with this regimen that Satoh et al. reported in the current issue of Gastric Cancer [5]. Data presented in this retrospective case series was promising, with a 2-year overall survival rate of 91% for stage III cancer, median survival time of 1.86 years for stage IV cancer, a downstaging rate of 59%, and a favorable toxicity profile with no treatment-related deaths. Based on these results, a phase III trial for stage III gastric cancer and a phase II trial for stage IV cancer have been launched to test a strategy of preoperative S1/CDDP and surgery followed by postoperative S-1. Past observations with other types of cancer indicate that a regimen with a pathologic complete response (pCR) rate above 10% should be used to ensure a Although surgery continues to play a central role in the treatment of gastric carcinoma, an optimal multidisciplinary approach has been under ongoing investigation to improve therapeutic outcomes. At the January 2006 Gastrointestinal Cancers Symposium, sponsored in part by the American Society of Clinical Oncology, debate focused on whether adjuvant therapy should be administered before or after surgery. Apparently, the intention was to compare the survival benefit of neoadjuvant chemotherapy as evidenced by the British MAGIC trial with that of postoperative chemoradiation established in the North American Intergroup 0116 study [1]. An obvious conclusion was that there was currently no way to answer this question, given that no randomized trial to directly compare these two strategies had been performed, but that each strategy clearly had its own theoretical merits and shortcomings. One disadvantage inherent in postoperative adjuvant therapies may be that this strategy can be offered only to a patient fortunate enough to have been treated with a potentially curative resection. This could be a drawback in the West because a greater proportion of gastric cancers in those countries are deemed unresectable at the time of diagnosis. In contrast, adequate chemotherapy given at the right time could downstage a tumor to such an extent that a locally advanced and unresectable cancer might respond and become resectable. There was one other Western randomized trial besides Intergroup 0116 in which a postoperative intervention significantly prolonged survival [2]. A striking feature observed in these two trials was that survival of patients treated by surgery alone was extremely poor — so poor, in fact, that the patients had in effect undergone noncurative surgery. This is not surprising in the case of 0116, however, if one considers the extent

Survival Benefits of Neoadjuvant Chemotherapy Followed by Radical Surgery versus Radiotherapy in Locally Advanced Chemoresistant Cervical Cancer

The aim of this study was to analyze long-term survivals in patients with stage IB to IIA cervical cancer treated by neoadjuvant chemotherapy setting. Between February 1989 and January 1998, 94 women with previously untreated stage IB to IIA carcinoma of the uterine cervix who received cisplatin based neoadjuvant chemotherapy were enrolled in this study. All of patients with chemoresponse (complete response, n=15; partial response, n=47) and 16 patients with chemoresistance received radical surgery (RS group). The other 16 patients with chemoresistance received radiotherapy for definite treatment (RT group). In the RS group, the 10 yr survival estimation in patients with bulky tumors (diameter ≥4 cm, n=26) was similar to that with non-bulky tumors (83.3% vs. 89.3%, p=NS). In selected patients with chemoresistance, those treated by radiotherapy (n=16) showed significantly poorer survivals than those treated by radical surgery (n=16) [10 yr survival rates of RT (25%) vs. RS (76.4%), p=0.0111]. Our results support that a possible therapeutic benefit of neoadjuvant chemotherapy plus radical surgery is only in patients with bulky stage IB to IIA cervical cancer. In cases of chemoresistance, radical surgery might be a better definite treatment option.