Contralateral Axillary Nodal Metastases: Stage IV Disease or a Manifestation of Progressive Locally Advanced Breast Cancer?

Background

Contralateral axillary nodal metastases (CAM) is classified as stage IV disease, although many centers treat CAM with curative intent. We hypothesized that patients with CAM, treated with multimodality therapy, would have improved overall survival (OS) versus patients with distant metastatic disease (M1) and similar OS to those with locally advanced breast cancer (LABC).

Methods

Using the NCDB (2004–2016), we categorized adult patients with node-positive breast cancer into three study groups: LABC, CAM, and M1. Kaplan-Meier curves were used to visualize the unadjusted OS. Cox proportional hazards models were used to estimate the association of study group with OS.

Results

A total of 94,487 patients were identified: 122 with CAM, 12,325 with LABC, and 82,040 with M1 (median follow-up 63.6 months). LABC and CAM patients had similar histology and rates of chemotherapy and endocrine therapy receipt. However, the CAM group had significantly larger tumors, more estrogen-receptor expression, higher T-stage, and more mastectomies than the LABC group. Compared with M1 patients, CAM patients were more likely to have grade 3 and cT4 tumors. Patients with CAM and LABC had similar 5-year unadjusted OS and significantly improved OS vs M1 patients. After adjustment, LABC and CAM patients continued to have similar OS and better OS vs M1 patients.

Conclusions

CAM patients who receive multi-modal therapy with curative intent may have OS more comparable to LABC patients than M1 patients. Out data support a reevaluation of whether CAM should remain classified as M1, as N3 may better reflect disease prognosis and treatment goals.

     

Which Gene is a Dominant Predictor of Response During FOLFOX Chemotherapy for the Treatment of Metastatic Colorectal Cancer, the MTHFR or XRCC1 Gene?

Background Combination chemotherapy using oxaliplatin, 5-fluorouracil and folinic acid (FOLFOX) is known to be effective in the treatment of metastatic colon cancer. Genes regulating the actions of 5-fluorouracil and oxaliplatin have been identified, but precisely which gene is dominant has not yet been determined. The aim of the investigation reported here was to identify which gene polymorphism is a dominant factor in FOLFOX chemotherapy–the methylenetetrahydrofolate reductase (MTHFR) gene for 5-fluorouracil or the X-ray cross-complementing1 (XRCC1) gene for oxaliplatin.Methods Paraffin-embedded tissues from 54 patients with unresectable metastases from colorectal cancer who had undergone chemotherapy with the FOLFOX regimen were analyzed for MTHFR polymorphisms in the MTHFR gene (677C➔T, Ala➔Val mutation) and XRCC1 gene (Arg➔Gln substitution in exon 10). Response rates and survivals were compared by types of polymorphism.Results Analyses of the patterns of MTHFR polymorphism revealed that 29.6% of the patients showed no mutation, 51.6% showed heterozygous mutations, and 11.8% showed homozygous mutations. Analyses of the XRCC1 polymorphism revealed that 60.8% of the patients showed no mutation, 31.4% showed heterozygous mutations, and 7.8% showed homozygous mutations. After four cycles of chemotherapy, 3.7% showed a complete response, 57.4% showed a partial response (PD) or stable disease, and 38.9% showed PD. The MTHFR polymorphism was not significant in predicting response and 30-month-survival (P > .1), whereas the XRCC1 polymorphism was a significant prognostic factor for both response (P = .038) and survival (P = .011).Conclusions We found a higher rate of mutations in the MTHFR gene than in the XRCC1 gene in Korean colorectal cancer patients. Response to FOLFOX was better in the patient group with mutations for MTHFR and worse in the patient group with mutations for XRCC1. However, only the XRCC1 polymorphism was a significant prognostic factor for the response to FOLFOX chemotherapy and short-term survival.     

Radical Prostatectomy for Incidental (Stage T1a–T1b) Prostate Cancer: Analysis of Predictors for Residual Disease and Biochemical Recurrence

Background

Controversies exist about the most appropriate management for patients with incidental prostate cancer after surgery for benign prostatic hyperplasia (BPH).

Objectives

To test the accuracy of preoperative clinical variables in predicting the presence of residual disease and biochemical recurrence in patients with incidental prostate cancer treated with radical retropubic prostatectomy.

Design, Setting, and Participants

We analyzed 126 T1a–T1b prostate cancers diagnosed at surgery for BPH between 1995 and 2007.

Intervention

All patients underwent radical retropubic prostatectomy within 6 mo of surgery for BPH.

Measurements

Univariate and multivariate logistic regression models addressed the association between the predictors (age, prostate-specific antigen [PSA] before and after surgery for BPH, T1a–T1b stage, prostate volume, and Gleason score at surgery for BPH) and the presence of residual cancer at radical retropubic prostatectomy. Cox proportional hazards regression analyses tested the relationship between the same predictors and the rate of biochemical recurrence after radical retropubic prostatectomy.

Results and Limitations

Seventy-five (59.5%) patients were stage T1a and 51 (40.5%) were stage T1b. At radical retropubic prostatectomy, 21 (16.7%) patients were pT0 and seven (5.6%) patients had extraprostatic disease (pT3). PSA before and after surgery for BPH and Gleason score at surgery for BPH were the only independent predictors of residual cancer at radical retropubic prostatectomy (all p < 0.04). Stage (T1a vs T1b) did not predict residual cancer or the rate of biochemical recurrence. With a mean follow-up of 57 mo, the 5- and 10-yr biochemical recurrence-free survival rates were 92% and 87%, respectively. PSA after surgery for BPH and Gleason score at surgery for BPH were the only significant multivariate predictors of biochemical recurrence (all p < 0.04). The main limitation of this study is the requirement of an external validation before implementation of the clinical recommendations.

Conclusion

PSA measured before and after surgery for BPH and Gleason score at surgery for BPH were the only significant predictors of the presence of residual cancer at radical retropubic prostatectomy. PSA measured after surgery for BPH and Gleason score at surgery for BPH were the only independent predictors of biochemical recurrence after radical retropubic prostatectomy.     

Merkel Cell Carcinoma: Assessing the Effect of Wide Local Excision,Lymph Node Dissection,and Radiotherapy on Recurrence and Survival in Early-Stage Disease—Results From a Review of 82 Consecutive Cases Diagnosed Between 1992 and 2004

Background Wide surgical excision, lymph node dissection, and radiotherapy have been used with varying efficacy in the management of early-stage Merkel cell carcinoma. Methods Records of 82 patients with early-stage Merkel cell carcinoma between 1992 and 2004 were reviewed. Results Forty-two patients developed a recurrence, and 44 died during the study period. Twenty-nine patients presented with regional lymph node disease, which was independently associated with diminished survival (hazard ratio [HR], 4.08; 95% confidence interval [CI], 1.55–10.75; P = .005). Lymphadenectomy was independently associated with prolonged disease-free survival (median, 28.5 vs. 11.8 months; HR, .46; 95% CI, .22–.94; P = .034) but not overall survival (P = .25). Margin-negative excision of the primary tumor (60 of 73) was not significantly associated with either prolonged disease-free survival (median, 16 vs. 14 months) or overall survival (median, 54 vs. 34 months). Forty-eight patients received radiotherapy: 36 to the primary site and 31 to the regional lymph nodes. Radiotherapy to both sites was associated with a longer median time to first recurrence (primary site, 24.2 vs. 11.8 months; regional lymph nodes, 46.2 vs. 11.3 months) and survival (primary site, 53.9 vs. 45.7 months; regional lymph nodes, 103.1 vs. 34.2 months). Administration of any radiotherapy was significantly associated with a prolonged time to first recurrence (HR, .39; 95% CI, .20–.75; P = .004) and survival (HR, .39; 95% CI, .18–.82; P = .013) on the Cox regression multivariate analyses. Conclusions Adjuvant radiotherapy to the primary site after surgical excision is recommended in early-stage disease. Involved regional lymph nodes should be treated with radiotherapy with or without lymphadenectomy.     

13th St. Gallen International Breast Cancer Conference 2013: Primary Therapy of Early Breast Cancer Evidence,Controversies, Consensus – Opinion of a German Team of Experts (Zurich 2013)

Zusammenfassung

Alle zwei Jahre findet in St. Gallen (Schweiz) die internationale Konsensuskonferenz zur Behandlung des primären Mammakarzinoms statt. Da sich das internationale Panel in St. Gallen aus Experten unterschiedlicher Länder zusammensetzt, spiegelt der Konsensus ein internationales Meinungsbild wider. Vor diesem Hintergrund erscheint es aus deutscher Sicht sinnvoll, die Abstimmungsergebnisse für den Therapiealltag in Deutschland zu konkretisieren. Eine deutsche Arbeitsgruppe mit acht Brustkrebsexperten, von denen zwei Mitglieder des internationalen St. Gallen-Panels sind, hat daher die Abstimmungsergebnisse der St. Gallen-Konsensuskonferenz (2013) für den Klinikalltag in Deutschland kommentiert. Inhaltliche Schwerpunkte der diesjährigen St. Gallen-Konferenz waren operative Fragestellungen der Brust und der Axilla, strahlentherapeutische und systemische Therapieoptionen sowie die klinische Relevanz der Tumorbiologie. Intensiv diskutiert wurde der klinische Einsatz von Multigen-Assays, inkl. ihrer Bedeutung für die individuelle Therapieentscheidung.     

Evidence-based medicine, cost-containment, care effectiveness: is it a new trilogy aimed at transforming the surgical mystique or the reality of double standards?

Clinically relevant attitudes and guidelines issued by a rational Evidence-Based Medicine (EBM) approach integrate individual clinical expertise with the best available external clinical evidence from systematic research. However, many surgeons, while considering the ultraliberal world they are practicing in and fearing that the primary goal of managed care in a market environment is reducing cost in order to make profit or decrease spending, remain suspicious of this kind of tentative protocol-driven medicine when applied to surgical practice. If surgeons want to develop a health policy agenda that emphasizes patient care issues above provider's or payor's interests, they should also enhance education programs, improve continuing objective assessment of the way surgery is performed, face moral issues raised by innovation, and assume an increased leadership role in sound critical evaluation of nonvalidated new techniques. They should no more consider EBM as a weapon turned against the surgical profession, but as a tool that may provide some answers to chronically unresolved questions in the evolving art of surgery.     

Cement leakage as a possible complication of balloon kyphoplasty—is there a difference between osteoporotic compression fractures (AO type A1) and incomplete burst fractures (AO type A3.1)?

Background  

Besides the treatment of osteoporotic vertebral compression fractures of AO type A1, balloon kyphoplasty (BKP) is seen as a therapeutic option even in the treatment of incomplete osteoporotic burst fractures (AO type A3.1). However, due to involvement of the posterior vertebral body wall, the risk of cement leakages is considered to be higher. This study focuses on the frequency and pattern of cement leakages in AO type A3.1 fractures compared with osteoporotic compression fractures (AO type A1).