Primary Systemic Chemotherapy Research Articles

Significance of Metabolic Tumor Volume at Baseline and Reduction of Mean Standardized Uptake Value in 18F-FDG-PET/CT Imaging for Predicting Pathological Complete Response in Breast Cancers Treated with Preoperative Chemotherapy

BackgroundThe usefulness of 18F-fluorodeoxyglucose-positron emission tomography/computed tomography for evaluating the treatment efficacy of breast cancers is well-established; however, the predictive values of parameters such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG) remain unknown.MethodsThis study examined 199 breast cancers treated with primary systemic chemotherapy (PSC) followed by operation, and determined the values of maximum standardized uptake value (SUVmax), peak SUV (SUVpeak), mean SUV (SUVmean), MTV, and TLG at baseline. Among these cases, data on early changes in these metabolic parameters in 70 breast cancers were also assessed.ResultsA pathological complete response (pCR) was achieved in 64 breast cancers. Breast cancers with low MTV at baseline had a significantly higher pCR rate than breast cancers with high MTV (47.9% vs. 23.4%; p = 0.0005). High reduction rates (∆) of SUVmax (p = 0.0001), SUVpeak (p = 0.0001), and SUVmean (p < 0.0001) resulted in an increased pCR compared with those for low ∆. The pCR rate was highest for the combination of low MTV and high ∆SUVmean (86.7%), and lowest for high MTV and low ∆SUVmean (15.4%); the remaining combinations were intermediate (58.6%; p < 0.0001). The combination of low MTV at baseline and high ∆SUVmean was a significant and independent predictor for pCR (odds ratio 28.63; 95% confidence interval 1.94–422.42; p = 0.0146) in multivariable analysis.ConclusionsLow levels of MTV at baseline and a high reduction of SUVmean after PSC was significantly associated with pCR. These findings suggest the usefulness of these metabolic parameters for predicting the treatment efficacy of breast cancers.

Abstract OT2-07-05: A phase III trial to compare eribulin mesylate + trastuzumab (H) + pertuzumab (P) with paclitaxel or docetaxel + HP for HER2-positive advanced or metastatic breast cancer (JBCRG-M06/ EMERALD)

Abstract Background: Docetaxel + Trastuzumab (H) + Pertuzumab (P) provided progression-free survival (PFS) and overall survival (OS) benefits in HER2-positive advanced or metastatic breast cancer (AMBC) in the CLEOPATRA study as a first-line therapy. However, long-term administration of docetaxel at a dose of 75 mg/m2 every 3 weeks in AMBC patients (pts) is difficult due to the toxicities. Eribulin mesylate (E) is a well-tolerated microtubule inhibitor, and we have reported the efficacy and safety of EHP regimen as first- and second-line therapy for AMBC in a multicenter, phase II study (JBCRG-M03/UMIN000012232). In this M06 study, we address the clinical question as to which is the better chemotherapy partner for HP as first line regimen, in terms of efficacy, toxicity and QOL. Methods: JBCRG-M06 is a multicenter open-label randomized phase III study for HER2-positive AMBC pts who have received no prior chemotherapy except for the HER2- Antibody-Drug Conjugate (ADC). Pts will be randomized 1:1 to E (1.4mg/m2 on day 1 and 8) + H (8 mg/kg loading dose followed by 6 mg/kg) +P (840 mg loading dose followed by 420 mg) q3wks or standard taxanes (docetaxel 75mg/m2 on day1 or paclitaxel 80mg/m2 on day 1, 8 and 15) + HP q3wks. Stratification factors for randomization are; presence of visceral metastases, number of prior taxanes on perioperative adjuvant treatment, and treatment with prior anti-HER2-ADC. Primary endpoint is PFS and secondary endpoints include overall response rate, duration of response, OS, patient-reported outcomes (PRO) relating to QOL and peripheral neuropathy, new-metastases free survival, and safety. Translational research to search for biomarker for individual precision therapy will be performed. Main eligibility criteria are as follows: pts with HER2-positive AMBC, female aged 20-70 years old, ECOG PS of 0-1, LVEF ≥ 50% at baseline and adequate organ function. Pts who had progressive MBC within 6 months after the end of primary adjuvant systemic chemotherapy are excluded. The sample size was calculated by type1 error (2-sided) of 0.05 and 80% power to estimate the noninferiority margin 1.33 with an expected median PFS of 14.2 months. The target number of pts is 480 recruited over the duration of 3-years. The first patient in was achieved on August 2017. (ClinicalTrials.gov Identifier:NCT03264547). Citation Format: Masuda N, Yamashita T, Saji S, Araki K, Ito Y, Takano T, Takahashi M, Tsurutani J, Koizumi K, Kitada M, Kojima Y, Sagara Y, Tada H, Iwasa T, Kadoya T, Iwatani T, Hasegawa H, Morita S, Ohno S. A phase III trial to compare eribulin mesylate + trastuzumab (H) + pertuzumab (P) with paclitaxel or docetaxel + HP for HER2-positive advanced or metastatic breast cancer (JBCRG-M06/ EMERALD) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT2-07-05.

RETINOBLASTOMA IN INDIA: Clinical Presentation and Outcome in 1,457 Patients (2,074 Eyes).

To study the clinical presentation, treatment, and outcome of patients with retinoblastoma (RB) in India. Retrospective study of 1,457 patients with RB (2,074 eyes). The mean age at presentation of RB was 29 months (median, 24 months; range, <1-370 months). There were 812 (56%) men and 645 (44%) women with unilateral presentation of RB in 57% (n = 834) and bilateral in 43% (n = 623). Familial RB was present in 4% (n = 55). The most common presenting complaints included leukocoria (n = 1,100; 75%), proptosis (n = 91; 6%), strabismus (n = 77; 5%), and red eye (n = 68; 5%). Most (n = 1,889; 91%) tumors were intraocular in location, and 185 (n = 185; 9%) had extraocular tumor extension at presentation. The most common modalities of primary treatment-included systemic chemotherapy (n = 1,171; 60%) and enucleation (n = 674; 35%). At a mean follow-up period of 44 months (median, 30 months; range, 3-234 months), 92% (n = 1,206) were alive, and 108 (8%) patients died because of RB. Based on Kaplan-Meier analysis, the survival at 1, 3, 5, and 10 years was 94%, 91%, 90%, and 89%, respectively. The most common presenting signs of RB in Asian Indian population are leukocoria and proptosis. With appropriate treatment, the survival rate is favorable at 92%.

BRCA1/2 Mutations and Bevacizumab in the Neoadjuvant Treatment of Breast Cancer: Response and Prognosis Results in Patients With Triple-Negative Breast Cancer From the GeparQuinto Study

Purpose BRCA1/2 mutations are frequent in patients with triple-negative breast cancer (TNBC). These patients are often treated with primary systemic chemotherapy. The aim of this study was to analyze the effects of BRCA1/2 mutations on pathologic complete response (pCR) and disease-free survival (DFS) in a cohort of patients with TNBC treated with anthracycline and taxane-containing chemotherapy, with or without bevacizumab. Patients and Methods Germline DNA was sequenced to identify mutations in BRCA1 and BRCA2 in 493 patients with TNBC from the GeparQuinto study. The pCR rates were compared in patients with and without mutation, as well as in patients treated with and without bevacizumab. In addition, the influence of BRCA1/2 mutation status and pCR status on DFS was evaluated relative to treatment. Results BRCA1/2 mutations were detected in 18.3% of patients with TNBC. Overall, patients with mutations had a pCR rate of 50%, compared with 31.5% in patients without a mutation (odds ratio [OR], 2.17; 95% CI, 1.37 to 3.46; P = .001). The pCR rate among patients treated with bevacizumab was 61.5% for BRCA1/2 mutation carriers and 35.6% for those without mutations (OR, 2.90; 95% CI, 1.43 to 5.89; P = .004). pCR was a strong predictor of DFS for patients without BRCA1/2 mutations (hazard ratio, 0.18; 95% CI, 0.11 to 0.31) but not for patients with BRCA1/2 mutations (hazard ratio, 0.74; 95% CI, 0.32 to 1.69). Conclusion The addition of bevacizumab may increase the pCR after standard neoadjuvant chemotherapy for patients with TNBC with BRCA1/2 mutations. In patients treated with anthracycline and taxane-based chemotherapy (with or without bevacizumab), pCR was a weaker predictor of DFS for BRCA1/2 mutation carriers than for patients without mutations.

Abstract No. 686 Retrospective comparison of radiofrequency ablation and microwave ablation for the treatment of colorectal liver metastases

Microwave (MWA) and radiofrequency (RFA) ablation are commonly used for the treatment of unresectable liver metastases from colorectal cancer (CRC). MWA has a few theoretical advantages over RFA (less heat sink, larger ablation zones, faster). However, limited data exists on this field. Our aim was to retrospectively analyse the safety and efficacy of MWA and RFA in the treatment of CRC liver metastases. Patients with unresectable CRC liver metastasis who were treated with RFA or MWA between March 2006 and December 2016 were included. Medical records and imaging studies were reviewed retrospectively for demographic data, to assess for local tumour recurrence and overall survival and to evaluate ablation-related adverse events. 456 ablations were performed in 193 patients (123 men) with a median age of 66 (range 32-91). The majority of patients had a history of surgery of the primary tumour (n=170, 88,1%) and systemic chemotherapy (n=183, 94,8%). 68 patients had a history of liver surgery (35,2%). RFA was used in 343 patients (75,2%), MWA in 113 (24,8%). Median number of procedures per patient was 2 (range 1-10). Median lesion size was 17mm (range 3-80mm). Mean follow-up per lesion was 2.0 years in the RFA group and 1.3 years in the MWA group. Local tumour recurrence rate was 45% for RFA and 28% for MWA, with a hazard ratio of 0.6 in favour of MWA (95%CI 0.4-0.9). Two and five year overall survival rates from time of diagnosis were 88% and 35% for RFA and 89% and 66% for MWA, respectively. Complications were reported in 43 of 456 ablations (9,4%); in 8,2% of RF ablations (n=28) and 13,3% of MW ablations (n=15). Complications classified as CTCAE grade 3 or higher were: haemothorax requiring surgery (n=1 for RFA), biloma (n=2 for RFA and MWA), biliary stricture (n=2 for RFA, n=1 for MWA), liver failure (n=2 for RFA), liver abscess (n=1 for RFA), pneumonia (n=2 for RFA) and pulmonary embolism (n=1 for RFA). Segmental portal vein occlusion was only seen with MWA (n=2). One patient died due to multi-organ failure post RFA. MWA could achieve better local tumour control compared with RFA in the treatment of CRC liver metastasis, with a slightly higher complication rate.

Percutaneous radiofrequency versus microwave ablation for the treatment of colorectal liver metastases.

401 Background: Microwave (MWA) and radiofrequency (RFA) ablation are commonly used for the treatment of unresectable liver metastases from colorectal cancer (CRC). MWA has a few theoretical advantages over RFA (active heating, less affected by heat sink effect, larger ablation zones, faster) however limited data exists on this field. Our aim was to analyse the safety and efficacy of MWA and RFA in the treatment of CRC liver metastases. Methods: All patients with unresectable CRC liver metastasis who were treated with RFA or MWA in a single center between March 2006 and December 2016 were included. Medical records and imaging studies were reviewed retrospectively for demographic data, to assess for local tumour recurrence and overall survival and to evaluate ablation-related adverse events. Results: 456 ablations were performed in 193 patients (123 men) with a median age of 66 (range 32-91). The majority of patients had a history of surgery of the primary tumour (n=170, 88,1%) and systemic chemotherapy (n=183, 94,8%). 68 patients had a history of liver surgery (35,2%). RFA was used in 343 procedures (75,2%) and MWA in 113 (24,8%). Median number of procedures per patient was 2 (range 1-10). Median lesion size was 17mm (range 3-80mm). Mean follow-up per lesion was 2.0 years in the RFA group and 1.3 years in the MWA group. Local tumour recurrence rate was 45% for RFA and 28% for MWA, with a hazard ratio of 0.6 in favour of MWA (95% CI 0.4-0.9). Two and five year overall survival rates from diagnosis of liver metastasis were 88% and 35% for RFA and 89% and 66% for MWA, respectively. Complications were reported in 43 of 456 procedures (9,4%); In 8,2% of RFAs (n=28) and 13,3% of MWAs (n=15). Complications classified as CTCAE grade 3 or higher were: haemothorax requiring surgery (n=1 for RFA), biloma (n=2 for RFA &amp; MWA), biliary stricture (n=2 for RFA and n=1 MWA), liver failure (n=2 for RFA), liver abscess (n=1 RFA), pneumonia (n=2 for RFA) and pulmonary embolism (n=1 RFA). Segmental portal vein occlusion was only seen with MWA (n=2; 1,8%). One patient died due to multi-organ failure post RFA. Conclusions: MWA could achieve better local tumour control compared with RFA in the treatment of CRC liver metastasis, with slightly higher complication rate.

Abundant tumor infiltrating lymphocytes after primary systemic chemotherapy predicts poor prognosis in estrogen receptor-positive/HER2-negative breast cancers.

The therapeutic effect of systemic treatment for breast cancer (BC) generally depends on its intrinsic subtypes. In addition, tumor infiltrating lymphocytes (TILs) are considered to be an independent factor for tumor shrinkage and disease prognosis. High TILs at baseline or after primary systemic chemotherapy are reported to be associated with better survival in triple-negative or human epithelial growth factor receptor 2 (HER2)-positive BCs. However, the prognostic value of TILs in estrogen receptor (ER)-positive and HER2-negative (ER+/HER2-) BC is still controversial. We assessed TIL score (low, intermediate, and high) before and after primary systemic chemotherapy in every subtype of BC, and compared the clinical outcomes. Biopsy specimens of 47 triple-negative, 58 HER2+ and 91 ER+/HER2- BCs were used to assess TILs before treatment. To assess TILs after treatment, we examined residual invasive carcinoma in surgically resected samples of 28 triple-negative, 30 HER2+ and 80 ER+/HER2- BCs. A high TIL score in triple-negative BC before treatment resulted in a significantly higher proportion of pathological complete response (pCR). In contrast, ER+/HER2- BC exhibited fewer instances of pCR than other subtypes. Although not statistically significant, ER+/HER2- cases with a high TIL score also tended to achieve pCR (p=0.088). Moreover, we revealed that low TIL BCs after chemotherapy, but not at baseline, had significantly better relapse-free survival in ER+/HER2- BC (p=0.034). Pathological examination of TILs after treatment may be a surrogate marker for prognosis in ER+/HER2- BC.

Comparison of irinotecan and oxaliplatin as adjuvant chemotherapy for patients with resectable synchronous colon cancer plus liver-confined metastases: A retrospective nationwide database study.

624 Background: Although irinotecan and oxaliplatin are both standard treatment for advanced colon cancer, it was unclear whether either was effective for patients with resectable synchronous colon cancer plus liver-confined metastasis (SCCLM) after curative surgery. Methods: We established a population-based cohort of patients diagnosed with de novo SCCLM between 2004 and 2009 by searching the database of Taiwan Cancer Registry and National Health Insurance Research Database of Taiwan. Patients who received curative surgery as the first therapy followed by chemotherapy doublets were classified into two groups: irinotecan group, or oxaliplatin group. Patient who received radiotherapy or did not receive chemotherapy doublets were excluded. Results: We included 6533 patients with de novo stage IV colon cancer, and 309 of them received chemotherapy doublets after surgery; 77 patients received irinotecan, and 232 patients received oxaliplatin as adjuvant chemotherapy. Patients in the irinotecan group and patients in the oxaliplatin group exhibited similar overall survival (OS) (median: not reached vs. 40.8 months, p = 0.151) and time to the next line of treatment (median: 16.5 months vs. 14.3 months, p = 0.349) in both univariate and multivariate analyses. Patients with resectable SCCLM had significant shorter median OS than patients with stage III colon cancer who received curative surgery and subsequent adjuvant chemotherapy but longer than patients with de novo stage IV colon cancer who received surgery only to the primary site and standard systemic chemotherapy ( p&lt; 0.001). Conclusions: Either irinotecan or oxaliplatin exhibited similar efficacy for patients who received curative surgery for resectable SCCLM. [Table: see text]

Long-term survival and prognosis associated with conversion surgery in patients with metastatic gastric cancer.

In gastric cancer, primary systemic chemotherapy is the standard approach for the management of patients with initially unresectable metastasis, and it occasionally leads to a reduction in the size of the lesion, which facilitates surgical resection. The aim of this study was to examine the prognosis of patients who were able to undergo complete resection following chemotherapy. A total of 10 patients who underwent radical surgery for stage IV primary gastric cancer after chemotherapy between 2009 and 2015 at the Department of Surgery of Hokkaido Social Work Association Obihiro Hospital (Obihiro, Japan) were retrospectively investigated. Three regimens were used (S-1, n=1; S-1 + cisplatin, n=8; and S-1 + docetaxel, n=1). The mean time from chemotherapy to surgery was 210 days. One total gastrectomy + splenectomy + colectomy, one total gastrectomy + splenectomy, four total gastrectomies and three distal gastrectomies were performed. There were two cases of pancreatic fistula formation postoperatively. All the patients survived for >1 year. Of the 10 patients, 5 survived without recurrence. The median survival time was 871.1 days after diagnosis. Therefore, curative resection after chemotherapy is associated with a better prognosis in stage IV gastric cancer patients.

Cancer-related multiple brain infarctions caused by Trousseau syndrome in a patient with metastatic colon cancer: a case report.

Thromboembolism that occurs in association with a malignant tumor is known as Trousseau syndrome. We herein present a case of Trousseau syndrome during systemic chemotherapy for metastatic colon cancer. A 65-year-old man with multiple liver metastases underwent primary tumor resection and systemic chemotherapy. Multiple brain infarctions were detected by magnetic resonance imaging immediately after first-line chemotherapy, which was deemed ineffective. There was no evidence of cardioembolic stroke or carotid atherosclerosis. Although the patient was initially asymptomatic, he subsequently developed paralysis. Despite anticoagulant treatment, he developed repeated recurrences of the infarction, and the area of the infarction spread as the liver metastases progressed. The patient’s condition showed no response to an alternative treatment regimen for advanced colon carcinoma. He died approximately 11 months after tumor discovery.

Ten-Year Outcomes of Patients With Breast Cancer With Cytologically Confirmed Axillary Lymph Node Metastases and Pathologic Complete Response After Primary Systemic Chemotherapy.

The long-term effect of axillary pathologic complete response (pCR) on survival among women with breast cancer treated with primary systemic chemotherapy (PST) is unknown. To assess the long-term effect of axillary pCR on relapse-free survival (RFS) and overall survival (OS) in women with breast cancer with cytologically confirmed axillary lymph node metastases treated with PST. We retrospectively analyzed the effect of axillary pCR on 10-year OS and RFS among all women who received a diagnosis of breast cancer stages II to III with cytologically confirmed axillary metastases between 1989 and 2007 who received PST at a large US comprehensive cancer center. Women were stratified by post-PST axillary status, and survival outcomes were estimated and compared according to response in the breast and axilla. Outcomes of interest were RFS and OS. Of 1600 women treated, median (range) age at diagnisis was 49 (21-86) years. A total of 454 (28.4%) achieved axillary pCR. These patients were more likely to have human epidermal growth factor receptor 2 (HER2)-positive and triple-negative disease (P < .001), pCR in the breast (P < .001), high-grade tumors (P < .001), and lower clinical and pathologic T stage (P = .002). Ten-year OS rates were 84% (95% CI, 79%-88%) and 57% (95% CI, 54%-61%) (P < .001) and 10-year RFS rates 79% (95% CI, 74%-83%) and 50% (95% CI, 46%-53%) (P < .001) for patients with axillary pCR and residual axillary disease, respectively. For patients with axillary pCR, 10-year OS rates were 90% (95% CI, 84%-94%) for those with breast pCR and 72% (95% CI, 61%-80%) for those with residual breast disease (P < .001). For patients with residual axillary disease, 10-year OS rates were 66% (95% CI, 56%-74%) for patients with and 56% (95% CI, 52%-60%) for patients without breast pCR (P = .02). Of patients receiving HER2-targeted therapy for HER2-positive disease, 67.1% (100 of 149) achieved axillary pCR; 10-year OS rates were 92% (95% CI, 84%-96%) and 57% (95% CI, 20%-82%) (P = .003) and 10-year RFS rates 89% (95% CI, 81%-94%) and 44% (95% CI, 18%-68%) (P < .001) for those with axillary pCR and residual axillary disease, respectively. Axillary pCR was associated with improved 10-year OS and RFS. Patients with axillary and breast pCR after PST had superior long-term survival outcomes. Patients undergoing HER2-targeted therapy for HER2-positive disease had high rates of axillary pCR, and those with axillary pCR had excellent 10-year OS.

Clinical significance of serum CA125 in diffuse malignant mesothelioma.

BackgroundMalignant mesothelioma (MM) is a rare and fatal neoplasm. For diffuse malignant mesothelioma (DMM) patients that were not suitable for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy, systemic chemotherapy is the main treatment. There are no convenient tumor markers to predict the efficacy of treatment and disease progression. This study aimed to evaluate serum CA125 level as a biochemical marker of response to therapy and prognosis in patients with DMM.MethodsA retrospective study was performed in a single medical institution from April 2008 to April 2014. Overall survival (OS) and prognostic factors were assessed.ResultsForty-one patients were included with a median age of 53 years. The median OS of all patients was 10 months. Patients with baseline CA125 > 280 U/ml had worse OS compared with the patients that baseline CA125 ≤ 280 U/ml. Baseline level of CA125, stage of disease, primary tumor location and systemic chemotherapy were independent prognostic factors associated with OS. In patients who received systemic chemotherapy, the decline in serum CA125 was associated with favorable OS and objective response according to modified Response Evaluation Criteria in Solid Tumors criteria.ConclusionsThe baseline level of serum CA125, accompanied with stage of disease, primary tumor location and systemic chemotherapy, could be regarded as independent prognostic factors for DMM patients. Otherwise, the change in serum CA125 can predict OS and response to systemic chemotherapy.

Primary systemic chemotherapy in locally advanced breast cancer- taxane versus non-taxane combination chemotherapy schedule

Background: Primary systemic chemotherapy (PST) forms a pivotal role in the management of primarily inoperable locally advanced breast cancer (LABC). Studies have revealed that complete pathologic response (pCR) is a surrogate marker of survival of LABC patients. In this study we aim to compare two chemotherapy regimens TAC vs. FAC/FEC. Endpoints are pCR and toxicity. Methods: 130 primarily inoperable LABC patients who received PST with either taxane containing chemotherapy TAC (Docetaxe l75 mg/m 2 , Adriamycin 50 mg/m 2 , Cyclophosphamide 500 mg/m 2 ) or non-taxane chemotherapy FAC (5-Flurouracil 500 mg/m 2 , Adriamycin 50 mg/m 2 , Cyclophosphamide 500 mg/m 2 )/FEC (5-Flurouracil 500 mg/m 2 , Epirubicin 100 mg/m 2 , Cyclophosphamide 500 mg/m 2 ) were prospectively observed and studied as two treatment arms- Taxane arm (70 patients) or Non-taxane arm (60 patients). Patients in each arm received maximum 6 cycles of taxane or non-taxane chemotherapy. Tumor response & toxicity was assessed. Results: 25.7% patients in taxane arm and 10% patients in non-taxane arm had complete pathological response (p=0.014). 90% in taxane arm and 86.7% in non-taxane arm became operable after PST (p=0.564). Grade 3 or 4 neutropenia was seen in 45.7% and 3.3% in Taxane and non-Taxane arm respectively (p=0.000). All patients completed the planned treatment in spite of the higher incidence of Grade 3/4 neutropenia in the docetaxel arm. Conclusions: TAC has significantly better complete pathologic response with tolerable toxicity. Hence in Indian LABC patients as well, taxane containing chemotherapy in the primary setting is the better option. Longer follow up of this study may confirm whether the better pathologic response may translate to better survival.

AXILLARY LYMPH NODE DISSECTION IN BREAST CANCER PATIENTS. THE ROLE OF SENTINEL LYMPH NODE BIOPSY

Rationale. Since its introduction in the early 1990s, sentinel lymph node biopsy (SLNB) is regarded as the standard treatment for patients with clinically negative axillary lymph nodes (LNs) on initial presentation. Classically, when the SLN biopsy is negative, the axillary LN dissection (ALND) is no further necessary. On the other hand, performing complete ALND in case of a positive SLNB is controversial, recent data from randomized controlled studies suggesting that, in these cases, the tumor biology has a greater impact on the adjuvant treatment decision than the completion of an ALND. Objective. The aim of this review is to ascertain whether axillary LN surgery has survival benefits in women with early breast cancer and SLN involvement, either micro-metastatic or macro-metastatic. Moreover, it tries to assess the value of SLN biopsy before and after primary systemic chemotherapy and its role in the staging of the axilla in locally recurrent breast cancer. Materials and method. We searched Pubmed, Medline, the Cochrane Register of Controlled Trials and G.I.N (Guidelines International Network) databases for English language articles about the need of ALND in women with both positive and negative SLNs using controlled vocabulary (e.g. “breast cancer”) and key words (e.g “sentinel lymph node”, “axilla dissection”). The analysis was restricted to retrospective studies and randomized controlled trials focusing on survival benefits in terms overall (OS) or disease-free survival (DFS). Conclusions. There is increasing evidence which indicates that ALND can be avoided in a specific group of patients with early breast cancer, even though the SLNB is positive. A correlation between the clinico-pathological features of the breast cancer and the probability of residual disease in the axilla, could allow the selection of cases in which ALND can be omitted. In the context of neo-adjuvant chemotherapy, it is not yet established if positive SLNs could be converted to negative SLNs after chemotherapy as the rate of false-negative results is still high.

Duodenal Adenocarcinoma: Profile and Predictors of Survival Outcomes

Duodenal adenocarcinoma is rare. We aimed to evaluate survival outcome and prognostic factors for survival in patients with duodenal adenocarcinoma in recent years, marked by advancement in chemotherapy for gastrointestinal cancers. All patients treated for duodenal adenocarcinoma at our institution between January 2000 and July 2013 were reviewed. Thirty-nine patients were identified: 27 operative patients [21(53.8%) curative and 6 (15.4%) palliative operations] and 12 nonoperative patients [primary systemic chemotherapy, 4 (10.3%), palliative radiotherapy, 1 (2.6%), and no treatment, 7 (17.9%)]. Curative resections included 13 pancreaticoduodenectomies and eight segmental resections. Median overall survival (OS) for entire cohort was 14.4 months. Median OS and one-, three-, and five-year OS were operative group (41.4 months; 79.1%, 50.6%, and 10.6%, respectively); nonoperative group (7.4 months; 25.0%, 8.3%, and 0%, respectively); curative surgery (45.4 months; 92.9%, 62.5%, and 16.7%, respectively) and palliative surgery (5.4 months; 33.3%, 16.7%, and 0%, respectively). Female gender (P = 0.04), curative resection (P = 0.03), nodal metastasis (P = 0.047) and advanced T stage (P = 0.047) were predictive of OS. Two factors were independently predictive of OS--female gender and curative resection. Overall survival still hinges on curative resection. This favors early detection. Adjuvant treatment modalities such as chemotherapy and radiation require further investigation.

Circulating Tumor Cells and Recurrence After Primary Systemic Therapy in Stage III Inflammatory Breast Cancer.

Inflammatory breast cancer (IBC) is rare and aggressive, with poor survival. While circulating tumor cells (CTCs) predict outcome in non-IBC patients, little data exists regarding their prognostic significance in IBC. This prospective study analyzed blood samples for CTCs from 63 stage III IBC patients to determine if CTCs present after primary systemic chemotherapy predicted relapse. CTC identification was not associated with tumor characteristics, lymph node positivity, or complete pathologic response to systemic therapy. At mean follow-up of 38 months, multivariable analysis demonstrated that detection of one or more CTCs predicted shortened relapse-free (log-rank P = 0.005, hazard ratio [HR] = 4.22, 95% confidence interval [CI] = 1.67 to 10.67, Cox P = 0.002) but not overall survival (log-rank P = 0.54, HR = 1.53, 95% CI = 0.41 to 5.79, Cox P = 0.53). All statistical tests were two-sided. In this study, CTCs after primary chemotherapy identified IBC patients at high risk for relapse.

Strategy for cStage4 colorectal cancer: Chemotherapy or resection of primary tumor?

779 Background: It is controversial that the primary tumor must be removed prior chemotherapy in cStage4 colorectal cancer, because some cases prognostic factor were metastatic sites. We report cases of cStage4 colorectal cancer which were underwent intrensive chemotherapy prior the primary tumor resection. Methods: 190 cases of metastatic colorectal cancer were treated by L-OHP based chemotherapy plus bevacizumab/cetuximab/panitumumab in September 2007 to June 2012. 56 cases were treated by intensive chemotherapy prior primary tumor resection, and 44 cases were underwent surgical resection of primary tumor after evaluation of chemotherapy response. Results: 38/10/8 cases were treated by bevacizumab/cetuximab/panitumumab with L-OHP combined therapy as intensive treatment. 30 patient with obstructed primary lesion were underwent stoma surgery (53.6%). Evaluable lesions except primary lesion were liver (50.0%), lung (12.5%), LNs (33.9%). Response rate of chemotherapy were 67.9% (PR/NC/PD: 38/14/4), and 44 cases were performed resection of primary lesion in PR and SD cases. Pathological G2 and G3 response in resected primary lesion were 18.4% (G1a/G1b/G2/G3:17/18/8/2). A GI perforation and bowel obstruction in chemotherapy and 3 cases of anastomotic leakage and 6 cases of SSI in perioperable period were observed respectively. Conclusions: It is seemed to contribute improvement of QOL and local control that start with systemic chemotherapy prior primary lesion resection, therefore some cStage4 cases were difficult to R0 resection also primary lesion and systemic chemotherapy could be reduced symptom with metastatic sites. Only 18.4% of the resected primary tumor were G2/3 pathological response by systemic chemotherapy, on the other hand preoperative chemo-radiation in rectal cancer accomplished 67.3% of G2/3 pathological response (in house data). The end-point of therapy in stage 4 colorectal cancer patient are QOL and prolong survival, and should be selected treatments depending on the patient condition.

Adjuvant Chemotherapy with S-1 in Breast Cancer Patients after Primary Systemic Chemotherapy

Additional therapy following definitive breast surgery after primary systemic chemotherapy (PSC) has not been correctly evaluated. Two unsolved problems regarding additional chemotherapy following PSC in advanced breast cancer are the subjects of this article. First is the prognostic impact of additional chemotherapy after surgery in patients with residual disease after completion of standard PSC, and second is the use of oral anticancer drugs such as S-1, which are known as metronomic chemotherapy, in this setting. Although there are many ongoing trials for breast cancer patients with residual disease after PSC in various subtypes, survival benefit has not been validated in clinical trials. Orally effective anticancer drugs such as S-1 and capecitabine can be further candidates for additional postoperative chemotherapy after PSC. Further studies are needed to evaluate the usefulness of these metronomic chemotherapies in this setting.

脾摘を先行し術前化学療法を行った肝硬変を有する炎症性乳癌の1例

脾摘を先行し術前化学療法を行った肝硬変を有する炎症性乳癌の1例

Prognostic relevance of induced and spontaneous apoptosis of disseminated tumor cells in primary breast cancer patients.

BackgroundAn imbalance between cell proliferation and programmed cell death can result in tumor growth. Although most systemic cytotoxic agents induce apoptosis in tumor cells, a high apoptotic rate in primary breast cancer correlates with poor prognosis. The aim of this study was to investigate the incidence and the prognostic significance of apoptotic disseminated tumor cells (DTC) in the bone marrow (BM) of breast cancer patients who either underwent primary surgery or primary systemic chemotherapy (PST).MethodsA total of 383 primary breast cancer patients with viable DTC in the BM were included into this study. Eighty-five patients were initially treated with primary systemic chemotherapy whereas 298 patients underwent surgery first. Detection of apoptotic DTC were performed by immunocytochemistry using the M30 antibody which detects a neo-epitope expressed after caspase cleavage of cytokeratin 18 during early apoptosis. The median follow up was 44 months (range 10–88 months).ResultsEighty-two of 298 (27%) primary operated patients and 41 of 85 (48%) patients treated with primary systemic systemic therapy had additional apoptotic DTC (M30 positive). In the neoadjuvant group M30-positive patients were less likely to suffer relapse than those without apoptotic DTC (7% vs. 23% of the events, p = 0.049). In contrast, the detection of apoptotic DTC in patients treated by primary surgery was significantly associated with poor overall survival (5% vs. 12% of the events, p = 0.008).ConclusionsApoptotic DTC can be detected in breast cancer patients before and after systemic treatment. The presence of apoptotic DTC in patients with PST may be induced by the cytotoxic agents. Thus, both spontaneous and chemotherapy-induced apoptosis may have different prognostic significance.