Postoperative CTX Research Articles

Alteration in the gut microbiome is associated with changes in bone metabolism after laparoscopic sleeve gastrectomy.

Laparoscopic sleeve gastrectomy (LSG), the most common bariatric surgical procedure, leads to durable weight loss and improves obesity-related comorbidities. However, it induces abnormalities in bone metabolism. One unexplored potential contributor is the gut microbiome, which influences bone metabolism and is altered after surgery. We characterized the relationship between the gut microbiome and skeletal health in severe obesity and after LSG. In a prospective cohort study, 23 adults with severe obesity underwent skeletal health assessment and stool collection preoperatively and 6mo after LSG. Gut microbial diversity and composition were characterized using 16S rRNA gene sequencing, and fecal concentrations of short-chain fatty acids (SCFA) were measured with LC-MS/MS. Spearman's correlations and PERMANOVA analyses were applied to assess relationships between the gut microbiome and bone health measures including serum bone turnover markers (C-terminal telopeptide of type 1 collagen [CTx] and procollagen type 1N-terminal propeptide [P1NP]), areal BMD, intestinal calcium absorption, and calciotropic hormones. Six months after LSG, CTx and P1NP increased (by median 188% and 61%, P< .01) and femoral neck BMD decreased (mean -3.3%, P< .01). Concurrently, there was a decrease in relative abundance of the phylum Firmicutes. Although there were no change in overall microbial diversity or fecal SCFA concentrations after LSG, those with greater within-subject change in gut community microbial composition (β-diversity) postoperatively had greater increases in P1NP level (ρ= 0.48, P= .02) and greater bone loss at the femoral neck (ρ= -0.43, P= .04). In addition, within-participant shifts in microbial richness/evenness (α-diversity) were associated with changes in IGF-1 levels (ρ= 0.56, P< .01). The lower the postoperative fecal butyrate concentration, the lower the IGF-1 level (ρ= 0.43, P= .04). Meanwhile, the larger the decrease in butyrate concentration, the higher the postoperative CTx (ρ= -0.43, P= .04). These findings suggest that LSG-induced gut microbiome alteration may influence skeletal outcomes postoperatively, and microbial influences on butyrate formation and IGF-1 are possible mechanisms.

Postoperative hepatic arterial chemotherapy after resection of colorectal liver metastases in patients at high risk of hepatic recurrence: A multicenter randomized phase II trial (PRODIGE 43 - PACHA-01).

3515 Background: Hepatic arterial infusion (HAI) of chemotherapy (CTx) has been proposed as a potential treatment to decrease the risk of hepatic recurrence after resection of colorectal liver metastases (CRLM). Randomized controlled trials (RCTs) led to controversial results and meta-analyses are inconclusive. We conducted a comparative phase II RCT to assess the efficacy of adjuvant HAI oxaliplatin with concomitant intravenous (IV) CTx in pts at high risk of hepatic recurrence (≥4 resected CRLM). Methods: Pts who underwent curative-intent surgery of at least 4 CRLM after preoperative IV CTx were randomly assigned (1:1) to receive adjuvant IV fluorouracil/leucovorin (LV5FU2) combined with oxaliplatin (85mg/m2) by HAI (HAI-IV arm) or IV route (IV arm) every 2 weeks, for at least 3 months to achieve a minimal duration of perioperative CTx of 6 months. The primary endpoint was the hepatic recurrence free survival (h-RFS). Secondary endpoints included the feasibility of delivering at least 4 CTx cycles, toxicity (NCI-CTCAE 4.0) including HAI catheter-related complications, RFS, overall survival (OS) and recurrence pattern. 108 randomized pts were required to detect a gain in 18-month h-RFS from 30% to 50% with a one-sided α risk of 10% and 95% power. The primary endpoint was analyzed with a Cox regression model, with adjustment for stratification factors (tumor response to preoperative CTx and number of resected CRLM). The study was prematurely stopped after randomization of 99 pts due to recruitment issues and HAI catheters market withdrawal. Results: Between Jun 2015 and Dec 2020, 99 pts (median age, 62; median number of CRLM, 5) were randomly assigned in HAI-IV arm (50 pts) or IV arm (49 pts). After a median follow-up of 56 months, the intent-to-treat analysis showed a significantly longer h-RFS in the HAI-IV arm compared to the IV arm (median 25 [16-37] vs 12 months [8-21]; HR 0.598 [95%CI 0.379-0.944], p = 0.027). 5-year h-RFS was 32% [19-45] in the HAI-IV arm vs 13% [4-27] in the IV arm, respectively. Median and 5-year OS were 74 months [51-74] and 60% [43-74] in the HAI-IV arm vs 54 months [37-69] and 46% [29-61] in the IV arm (HR 0.551 [0.299-1.015], p = 0.056). The median number of postoperative CTx cycles was 6 in both groups with 86% and 78% of patients having received at least 4 cycles in HAI-IV and IV arms (p = 0.7), respectively. Grade 3-4 toxicity rate was 58% in the HAI-IV arm vs 31% in the IV arm (p = 0.01). Overall, nine pts (18%) experienced HAI-related complications. No toxic death occurred in both arms. Conclusions: Despite a higher but acceptable toxicity, combination of HAI oxaliplatin with IV LV5FU2 significantly improved h-RFS after curative resection of CRLM in high-risk patients. This combined treatment should be considered as a valid option for these patients. Clinical trial information: NCT02494973 .

Long-Term Outcomes of Perioperative Versus Neoadjuvant Chemotherapy for Resectable Colorectal Liver Metastases: An International Multicentre Propensity-Score Matched Analysis with Stratification by Contemporary Risk-Scoring.

There is still debate regarding the principal role and ideal timing of perioperative chemotherapy (CTx) for patients with upfront resectable colorectal liver metastases (CRLM). This study assesses long-term oncological outcomes in patients receiving neoadjuvant CTx only versus those receiving neoadjuvant combined with adjuvant therapy (perioperative CTx). International multicentre retrospective analysis of patients with CRLM undergoing liver resection between 2010 and 2015. Characteristics and outcomes were compared before and after propensity score matching (PSM). Primary endpoints were long-term oncological outcomes, such as recurrence-free survival (RFS) and overall survival (OS). Furthermore, stratification by the tumour burden score (TBS) was applied. Of 967 patients undergoing hepatectomy, 252 were analysed, with a median follow-up of 45 months. The unmatched comparison revealed a bias towards patients with neoadjuvant CTx presenting with more high-risk patients (p = 0.045) and experiencing increased postoperative complications ≥Clavien-Dindo III (20.9% vs. 8%, p = 0.003). Multivariable analysis showed that perioperative CTx was associated with significantly improved RFS (hazard ratio [HR] 0.579, 95% confidence interval [CI] 0.420-0.800, p = 0.001) and OS (HR 0.579, 95% CI 0.403-0.834, p = 0.003). After PSM (n = 180 patients), the two groups were comparable regarding baseline characteristics. The perioperative CTx group presented with a significantly prolonged RFS (HR 0.53, 95% CI 0.37-0.76, p = 0.007) and OS (HR 0.58, 95% CI 0.38-0.87, p = 0.010) in both low and high TBS patients. When patients after resection of CRLM are able to tolerate additional postoperative CTx, a perioperative strategy demonstrates increased RFS and OS in comparison with neoadjuvant CTx only in both low and high-risk situations.

Re-evaluation of controversial issues in the treatment of cT3N0-2 rectal cancer: a 10-year cohort analysis using propensity-score matching

Although neoadjuvant treatment is thought to provide optimal local control for stage II and III rectal cancers, many patients have been reported cured by total mesorectal excision (TME), alone or with additional chemotherapy (CTX). This study retrospectively evaluated outcomes in 2643 patients with cT3N0-2 rectal cancers undergoing curative TME during 2005-2015. Recurrence and survival outcomes were measured in three propensity-score matched groups, consisting of patients who underwent preoperative chemoradiotherapy (CRT) with postoperative CTX (NAPOC), postoperative CRT (POCRT), and exclusively postoperative CTX (EPOCT). Near-complete or complete TME was conducted in more than 95.9% of patients and 80% of scheduled dose of postoperative CTX was completed in 99%. Except for higher SR rate in the POCRT group than the NAPOC group (p = 0.008), 5-year cumulative local and systemic recurrence (LR and SR) rates were 4.9% and 15.2% for cT3N0, and 4.2% and 21% for cT3N1-2 patients (LR, p = 0.703; SR, 0.065), respectively, with no significant differences associated with treatment exposure (p = 0.11-1). The 5-year cumulative disease-free (75.6% vs 65.7%, p = 0.018) and overall survival (87.1% vs 79.4%, p = 0.018 each) rates were higher in the NAPOC group than the POCRT group with cT3N1-2. However, any significant survival differences were not identified between the NAPOC and EPOCT groups according to tumor sub-stages or locations (p = 0.395-0.971). We found any treatment modalities including competent TME and postoperative adjuvant CTX efficiently reducing LR generating robust survival outcome in the propensity-matched cohorts, demanding further randomized controlled trials by clinical sub-stages II-III.

Adherence to Nutritional Supplementation Determines Postoperative Vitamin D Status, but Not Levels of Bone Resorption Marker, in Sleeve-Gastrectomy Patients.

Taking advantage of isomeric form of vitamin E in the supplement, adherence to supplement could be evaluated by changes in circulating α- and γ-tocopherol concentrations. Accordingly, effects of supplementation on postoperative nutrition and bone metabolism were studied in terms of adherence. Thirty-eight SG patients were all prescribed a postoperative nutritional supplement containing a low dose of vitamin D (600 IU) and calcium (200 mg). Blood samples were collected prior to (M0) and 6 months after (M6) surgery and concentrations of nutrients and C-terminal telopeptide of type I collage (CTX), a marker of bone resorption, were measured. Adherence and non-adherence were stratified according to change (△, M6-M0) in serum α-tocopherol concentrations (> 0 vs. ≤ 0, respectively). When M0 and M6 were compared, there were significant increases in serum concentrations of 25(OH)D, α-tocopherol and selenium, whereas there were reductions in parathyroid hormone, ferritin, and γ-tocopherol. At M6, the prevalence of vitamin D insufficiency (25(OH)D < 30 ng/mL) and high CTX were 72 and 26%, respectively. When comparison was made between adherence and non-adherence, only △25(OH)D concentrations, but no other nutrients nor postoperative CTX differed. Multiple linear regression demonstrated that postoperative vitamin D status was independently associated with its preoperative concentrations (β = 0.85, p < 0.001) and adherence (β = 0.52, p < 0.05). SG patients' adherence to supplementation, even with a low dose of vitamin D and calcium, determined vitamin D status but not bone resorption marker concentrations, at least within 6 months after surgery.

The postoperative part of perioperative chemotherapy fails to provide a survival benefit in completely resected esophagogastric adenocarcinoma

BackgroundBased on two benchmark studies perioperative chemotherapy (CTx) has become standard treatment for locally advanced esophagogastric adenocarcinoma (EGA) in Europe. However, only half of the patients in both studies actually received postoperative CTx (aCTx). Thus, we evaluated the prognostic impact of preoperative CTx (nCTx) and aCTx combined versus nCTx alone. Furthermore, we aimed to identify subgroups potentially beneficial of aCTx and factors associated with its non-administration. MethodsWe retrospectively analyzed 299 consecutive patients with EGA, who underwent complete resection (all M0, R0) after nCTx in our institution and were eligible for aCTx. Patients with and without aCTx were compared regarding clinicopathological data, treatment, morbidity, and long-term prognosis. Results129 patients (43.1%) did not receive aCTx. Administration of aCTx did not significantly improve overall (OS) and recurrence free survival (RFS) (median OS: 78.2 months vs. not reached, p = 0.331; RFS: 43.3 vs. 41.1 months, p = 0.118), but was an independent positive predictor of RFS (HR 1.6 95%CI 1.1–2.5, p = 0.024). aCTx improved RFS in non-intestinal tumors (p = 0.023) and patients receiving FLOT regimen (p = 0.038). By logistic regression analysis factors predictive of non-administration of aCTx were older age (>65 years: OR 3.2, p = 0.028), longer hospital stay (15–28 days: OR 2.6, p = 0.001; >28 days: OR 5.2, p < 0.001), and histopathologic non-response (OR 1.9, p = 0.023). ConclusionAdvanced age, histopathologic non-response, and prolonged convalescence due to postoperative morbidity lead to omission of aCTx. However, this study could not provide evidence to support the beneficial role of aCTx in perioperative chemotherapy regimens for a selected patient collective with EGA and excellent prognosis.

Original article: role of adjuvant chemotherapy in a perioperative chemotherapy regimen for gastric cancer.

BackgroundMultimodal treatment strategies – perioperative chemotherapy (CTx) and radical surgery – are currently accepted as treatment standard for locally advanced gastric cancer. However, the role of adjuvant postoperative CTx (postCTx) in addition to neoadjuvant preoperative CTx (preCTx) in this setting remains controversial.MethodsBetween 4/2006 and 12/2013, 116 patients with locally advanced gastric cancer were treated with preCTx. 72 patients (62 %), in whom complete tumor resection (R0, subtotal/total gastrectomy with D2-lymphadenectomy) was achieved, were divided into two groups, one of which receiving adjuvant therapy (n = 52) and one without (n = 20). These groups were analyzed with regard to survival and exclusion criteria for adjuvant therapy.ResultsPostoperative complications, as well as their severity grade, did not correlate with fewer postCTx cycles administered (p = n.s.). Long-term survival was shorter in patients receiving postCTx in comparison to patients without postCTx, but did not show statistical significance. In per protocol analysis by excluding two patients with perioperative death, a shorter 3-year survival rate was observed in patients receiving postCTx compared to patients without postCTx (3-year survival: 71.2 % postCTx group vs. 90.0 % non-postCTx group; p = 0.038).ConclusionThese results appear contradicting to the anticipated outcome. While speculative, they question the value of post-CTx. Prospectively randomized studies are needed to elucidate the role of postCTx.

Is primary surgery without preoperative chemotherapy the best treatment option for signet ring cell esophagogastric adenocarcinomas?

106 Background: Recent retrospective multicentric data favor a primary resection without neoadjuvant chemotherapy for signet ring cell (SRC) gastric cancer. Aim of this retrospective exploratory study is the comparison of primary resected with neoadjuvantly treated locally advanced SRC esophagogastric adenocarcinomas (EGA) in respect of outcome. Methods: From 2002-2012 200/646 resected EGA were classified as SRC by WHO classification (more than 50% signet ring cells) and staged cT3/4 Nany M0/x. Clinical response evaluation was based on endoscopy and CT-scan and histopathological regression was based on the Becker score (&lt;10% residual tumor cells: responder). UICC 7th was used. Analysis was retrospectively from a prospective data base. Results: 103 were treated by preoperative chemotherapy (CTx), 97 were primary resected. 73 (37%) had AEG, 127 (63%) gastric cancer. Postoperative CTx was delivered in 62/103 (60%) of the patients with preoperative CTx and in 51/97 (53%) of the primary resected patients (p=0.28). In-hospital mortality was 4.5% (9/200). 20 (20%) were classified as clinical, 15 (8%) as histopathological responders. Preoperative CTx was significantly associated with worse pretherapeutic cT- (p=0.005) and cN- (p=0.008) categories, but subsequent lower (y)pN-category (p=0,001) and improved lymphnode ratio (p=0.001). Overall survival was significantly improved after preoperative CTx compared to primary resection (median survival 30.2 versus 17.6 months, p=0.001). Median survival of responding patients is not reached, median survival of nonresponder was 24.4 months (identical for clinical and histopathological responders) compared to 17.6 months in primary resected patients (p=0.002). The positive prognostic effect of preoperative CTx was significantly higher in AEG (p=0.004) compared to gastric cancer (p=0.067). In the 119 completely resected patients the survival was significantly improved by preoperative CTx (p=0.005), but it was no independent prognostic factor. Conclusions: A pre/periopative CTx seems also to be justified in SRC EGA. Relevant limitations are the retrospective and non-randomized design.

Resectability and indication for chemotherapy in patients with colorectal liver metastases as assessed by medical oncologists and surgeons.

e14167 Background: Multidisciplinary treatment in patients with colorectal liver metastases (CRLM) is standard in modern oncology. However, for interdisciplinary discussion assessing complimentary disciplines' potential and changes in personal views is crucial. We evaluated experienced medical oncologists' (MO) and surgeons' (SG) assessment of resectability and indication for chemotherapy (CTx) in patients with CRLM. Methods: Thirty patients who underwent R0-resection of CRLM between 2001 and 2011 at our department were selected. Medical history and staging data were presented to MO (n=10) and SG (n=11) in a virtual tumor board (TB1). Standardized blinded TED-voting answers (9 options) included assessment of resectability and the indication for pre- and/or postoperative CTx. The virtual tumor board was followed by training in terms of state-of-the-art lectures on potential of CTx and surgery. Assessment was then repeated in a second virtual tumor board (TB2). Results: 630 (21x30) answers were obtained per tumor board. In TB1 resectability, borderline resectability and definite unresectability were expected in 433, 161 and 36 answers, respectively. Resectability was significantly more often expected by SG (p&lt;0.001). In TB2 57% of answers were different from TB1 (p&lt;0.001). Assessment shifted from borderline resectable to resectable CRLM in 81 of 161 and from unresectable to (borderline) resectable CRLM in 29 of 36 answers (p&lt;0.001). The shift was significant in MO (p=0.012) and SG (p&lt;0.001). Preoperative CTx was significantly more often indicated by MO (p=0.041) and included in 255 answers (44%) in TB1 compared to only 157 answers (27%) in TB2 (p&lt;0.001). With 55% of answers voting for postoperative CTx remained stable in TB1 and TB2 without a significant difference between MO and SG in either TB1 (p=0.099) or TB2 (p=0.353). Conclusions: Resectability and indication for pre- but not postoperative CTx were discrepantly assessed by MO and SG. Training had a strong influence on decision making in MO and SG resulting in a higher rate of patients deemed (borderline) resectable. Furthermore, following training MO and SG opted less often for preoperative CTx.

Postoperative adjuvant chemotherapy (CTX) use in patients (Pts) with stage II/III rectal cancer treated with neoadjuvant therapy: A National Comprehensive Cancer Network (NCCN) analysis.

3515 Background: Practice guidelines recommend that patients who receive neoadjuvant chemotherapy and radiation for locally advanced rectal cancer complete postoperative systemic chemotherapy irrespective of tumor downstaging. Methods: We used the NCCN Colorectal Cancer (CRC) Database which tracks longitudinal care for patients treated at 8 specialty cancer centers to evaluate how frequently rectal cancer pts treated with neoadjuvant chemoradiation receive postoperative systemic CTX. We examined patient and tumor characteristics associated with adjuvant CTX in a multivariable logistic regression model. Results: Between September 2005 and February 2010, 1,441 pts with stage II/III rectal cancer were enrolled. Of these, 810 pts received neoadjuvant chemoradiation and were included in the analysis. Of these, 159 pts (20%) did not receive any adjuvant CTX. For those seen by a medical oncologist, the most frequent reason chemotherapy was not recommended was due to co-morbid illness (54%) and the most frequent reason chemotherapy was not received even though it was recommended or discussed was due to patient refusal (73%). Pts who were more likely to have no adjuvant CTX administered included: age 75+ (OR=11.4, p<0.0001), ECOG PS ≥ 1 (OR=3.1, p=0.0009), on Medicaid or indigent (OR=3.6, p=0.02), complete pathologic response (cPR; OR=2.4, p=0.02), abnormal CEA post-operatively (OR=2.2, p<0.0001), unavailable CEA post operatively (OR=3.4, p<0.0001), presence of re-operation/wound infection (OR=2.7, p=0.03), and no closure of ileostomy/colostomy (OR=1.9, p=0.01). Conclusions: Even at specialty cancer centers, a sizeable minority of rectal cancer patients treated with curative intent neoadjuvant chemoradiation do not complete postoperative CTX. Strategies to foster adherence to the third and final component of curative intent treatment are necessary.

10-year Results of Adjuvant Radiotherapy after Radical Prostatectomy in pT3N0 Prostate Cancer (EORTC 22911)

complete response (pCR) are needed. Based on phase I data, SWOG designed a phase II trial (S0356) to test OXP with PI5FU and EBRT for PTS with EA. Objectives included pCR $ 25%, acceptable toxicity (TOX), PFS, OS and exploration of molecular parameters relevant to pCR. Materials/Methods: Eligibility: clinical stage II/III EA, $ 18 years, Zubrod PS # 2, standard hematologic/non-hematologic values, and tumor # 2 cm into the gastric cardia. OXP 85 mg/m 2 was given day (d) 1, 15, and 29; PI5FU 180 mg/m 2 /d was given d 8-d43. EBRT 180 c Gy/d started d 8 x 25 fractions, 5 d/week to total dose 4500 c Gy. S was planned 2-4 weeks after NACMTx, with a second cycle of OXP/ PI5FU after S. Central pathology review of surgical specimens was mandated. The trial used a 2-stage design; the trial was halted at 45 PTS to review pCR rate; it reopened to full accrual. Results: Ninety-eight PTS enrolled between 9/15/04 and 8/18/08. Six PTS were ineligible; 2 PTS did not receive therapy (TX). Ninety PTS, 84 men (93%), median age 61.7 years, were analyzed. Four deaths (4.5%) were due to protocol TX; 2 due to NACMTX, 2 to S. Forty-three percent and 18% of PTS had grade 3/4 toxicity, respectively: 39% GI, 22% flu-like/fatigue, 17% pulmonary, 16%, hematologic, 14% mucositis and 3% neurologic. Seventy-seven PTS (86%) underwent S. 30 PTS (33%) had pCR at treating institution; 4 of these patients were found to have residual cancer by central pathology review. Twelve PTS (10%) had in situ cancer or T1N0M0. 50% received postoperative CTX. At 2 years, survival is $ 55%. Conclusions:OXP,PI5FU,andEBRTforPTSwithEAhasproducedthehighestpCRratereportedtodateforacooperativegroup trial. Significant but manageable non-hematologic TOX was observed. S mortality is acceptable. Future trials built on this platform shouldplantocompleteallTXbeforeS. TrialsusingpCRasanendpointrequirecentralpathologyreview.Furtherdata onPFSand OS will follow.

Oxaliplatin (OXP) plus protracted infusion 5-fluorouracil (PIFU) and external beam radiation (EBRT) prior to surgery (S) for potentially curable esophageal adenocarcinoma (EA): A Southwest Oncology Group (SWOG) phase II trial with molecular correlates (S0356)

4513 Background: Although neoadjuvant combined modality therapy (NACMTX) has become a standard of care in the United States, median overall survival (OS) for patients (PTS) with EA has changed little over the past 25 years. Progression free survival (PFS) and OS after NACMTX depend on extent of primary tumor response. New regimens to increase pathologic complete response (pCR) are needed. Based on phase I data, SWOG designed a phase II trial (S0356) to test OXP with PI5FU and EBRT for PTS with EA. Objectives included pCR rate ≥ 25%, acceptable toxicity (TOX), PFS, OS and exploration of molecular parameters relevant to pCR. Methods: Eligibility: clinical stage II/III EA, ≥ 18 years, Zubrod PS ≤ 2, standard hematologic/non-hematologic values, and tumor &lt; 2 cm into the gastric cardia. OXP 85 mg/m2 was given day (d) 1, 15 and 29; PI5FU 180 mg/m2/d was given d 8-d43. EBRT 180 cGy/d started d 8 x 25 fractions, 5 d/week to total dose 4500 cGy. S was planned 2–4 weeks after NACMTX, with a second cycle of OXP/ PI5FU after S. Central pathology review of surgical specimens was mandated. The trial used a 2-stage design; the trial was halted at 45 PTS to review pCR rate; it reopened to full accrual. Results: 98 PTS enrolled between 9/15/04 and 8/18/08. 6 PTS were ineligible; 2 PTS did not receive therapy (TX). 90 PTS, 84 men (93%), median age 61.7 years, were analyzed. 4 deaths (4.5%) were due to protocol TX; 2 due to NACMTX, 2 to S. 43% and 18% of PTS had grade 3/4 toxicity, respectively: 39% GI, 22% flu-like/fatigue, 17% pulmonary, 16% hematologic, 14% mucositis and 3% neurologic. 77 PTS (86%) underwent S. 30 PTS (33%) had pCR. 9 PTS (10%) had in-situ cancer or T1N0M0. &lt;50% received postoperative CTX. Conclusions: OXP, PI5FU and EBRT for PTS with EA has produced the highest pCR rate reported to date for a cooperative group trial. Significant but manageable non-hematologic TOX was observed. S mortality is acceptable. Future trials built on this platform should plan to complete all TX before S. Tumor molecular profiles (analyses in progress) may predict benefit from this treatment. Data on PFS and OS will follow. [Table: see text]

Long-term survival of patients with colorectal liver metastasis (CLM) receiving liver resection (LR): Survival and prognostic factors (PF) of 257 patients

4079 Background: LR is currently the curative approach of CLM. Validated PF are helpful for decisions regarding primary surgery and chemotherapy of CLM. The question of adjuvant ctx after LR is still open. The aim of the study was to analyze PF for survival after resection of CLM. Methods: Consecutive pts with CLM and LR were studied. Between 01/1990 and 12/2003 a total of 257 pts with CLM (colon 121, rectal ca 136) received LR in a Munich CRC center. 106 pts had synchrone and 151 had metachrone CLM. After LR of CLM 155 (60%) out of 257 received Ctx. Results: Post-op mortality was 1.2% (3/257). Median survival after LR was 55.6 mo with a 5-ys of 47.1% and a 10-ys survival of 18.1 %. Median (55.8 vs 55.7 mo) and 5-ys OS (46.3 vs 47.6 mo) did not differ between syn- or metachrone LM. Initial LN status of pts with CLM was pN0 in 115/256 pts, while this was pN1 in 67 pts, pN2 in 43 and pN3 in 28. LN-status was associated with inferior OS. Median OS was 64.7 mo in pN0, while this was 53.8 in pN1, 41.2 in pN2 and 32.0 mo in pN3 pts with a 5-ys survival of 58% for pN0, 46.7% for pN1, 42.9% for pN2 and 21.4% for pN3 respectively (p=0.0025). A R0 LR of CLM was performed in 167/256, while this was R1 in 20, R2 in 11 and Rx in 59 pts. Pts with R0 resection had an OS of 65.4 mo, while this was significantly inferior in R1 (24.4 mo) and R2 resections (19.9 mo; p=0.0001). LM number (1 vs 2–3 vs >4) was associated with a worsening median (65.4 vs 48.1 vs 41.2 mo) and 5-ys survival (55.4 vs 37.9 vs 29.1 mo; p=0.0012). LM size ( <5 vs 5–10 >10 cm) was associated inversely with median (60.2% vs 42.9% vs 30.2%) and 5-ys OS (50.9% vs 39.8% vs 0%; p=0.0007). Adjuvant Ctx following LR improved median (63.6 vs 47.5 mo) as well as 5- ys OS (54.1% vs 39.1%). A total of 64 of 256 pts remained free of disease (med OS 136 mo) while 45 had new metachrone LM, 87 had LM and extrahepatic M and only 26 pts had a extrahepatic distant M. Conclusions: No difference in OS was observed between pts with syn- or metachrone CLM, while an increasing number and size of LM was associated with a worsening OS. Postoperative ctx after LR of CLM improved 5-ys survival and should be investigated in further trials. No significant financial relationships to disclose.

The influence of neoadjuvant chemotherapy on surgeon practice patterns for stage II breast cancer patients

INTRODUCTION: Neoadjuvant chemotherapy (NeoCTX) is standard management for locally advanced breast cancer. Phase III clinical trials reveal equivalent survival and improved breast conservation surgery (BCS) eligibility in Stage II breast cancer patients receiving neoCTX compared to postoperative CTX. Controversy persists regarding optimal integration of sentinel lymph node biopsy (SLNBx) into neoCTX protocols. We evaluated evolving surgical practice patterns regarding neoCTX, BCS, and SLNBx for Stage II breast cancer.

Multimodality Therapy Including Radiotherapy and Chemotherapy Improves Event-Free Survival in Stage C Esthesioneuroblastoma

To evaluate the efficacy of multimodality therapy in patients with esthesioneuroblastoma (ENB). From 01/1979 through 08/2001, 47 patients with ENB (20 men, 27 women, age 5-81 years), were registered from 18 oncologic centers. There were 14 tumors stage B and 33 stage C according to the Kadish classification. Initial treatment included surgery alone in seven patients, radiotherapy (RT) with or without chemotherapy (CTX) in twelve, surgery plus postoperative RT in 15, and multimodality therapy (surgery plus pre- or postoperative CTX plus postoperative RT) in 13. The 5-year overall survival (OS) for the whole group was 64 +/- 8% and the 5-year event-free survival (EFS) 50 +/- 8%. Patients with multimodality treatment had a significantly better 5-year EFS (74 +/- 13%) compared to the other patients (41 +/- 9%; p = 0.05), while the 5-year OS was not significantly different between the treatment groups (p = 0.39). For patients with Kadish stage C, multimodality therapy (n = 11) resulted in superior 5-year EFS (72 +/- 14% vs 17 +/- 9%; p = 0.01). These patients tended to have an improved OS (69 +/- 15% vs 47 +/- 12%; p = 0.19) compared to the other treatment groups. None of the patients with multimodality treatment had a metastatic relapse. Multimodality treatment (surgery plus pre- or postoperative CTX plus postoperative RT) appears to be highly efficient in preventing local and systemic relapse in patients with advanced ENB. Timing and optimal agents of CTX need to be further evaluated.