Lawrence D. Wagman

Contralateral prophylactic mastectomy improves the outcome of selected patients undergoing mastectomy for breast cancer

BACKGROUND Risk factors for contralateral breast cancer (CBC) may indicate a benefit for contralateral prophylactic mastectomy (CPM) at the time of unilateral mastectomy for breast cancer. The purpose of this study is to evaluate the efficacy of CPM in preventing CBC. METHODS sixty-four patients undergoing CPM and a control group of 182 patients not undergoing CPM and matched for age, stage, surgery, chemotherapy, and hormonal therapy were retrospectively compared for CBC rate, disease-free survival, and overall survival. RESULTS Thirty-six CBCs occurred in the control group. In the CPM group, 3 CBCs were found at the time of prophylactic mastectomy, but none occurred subsequently (P = 0.005). Disease-free survival at 15 years in the CPM group was 55% (95% confidence interval [CI] 38% to 69%) versus 28% (95% CI 19% to 36%) in the control group (P = 0.01). Overall survival at 15 years was 64% (95% CI 45% to 78%) CPM versus 48% (95% CI 39% to 58%) in controls (P = 0.26). CONCLUSION CPM prevented CBC and significantly prolonged disease-free survival. Future studies will need to address risk assessment and contralateral breast cancer prevention in patients treated for early breast cancer.

Primary mFOLFOX6 Plus Bevacizumab Without Resection of the Primary Tumor for Patients Presenting With Surgically Unresectable Metastatic Colon Cancer and an Intact Asymptomatic Colon Cancer: Definitive Analysis of NSABP Trial C-10

PURPOSE Major concerns surround combining chemotherapy with bevacizumab in patients with colon cancer presenting with an asymptomatic intact primary tumor (IPT) and synchronous yet unresectable metastatic disease. Surgical resection of asymptomatic IPT is controversial. PATIENTS AND METHODS Eligibility for this prospective, multicenter phase II trial included Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1, asymptomatic IPT, and unresectable metastases. All received infusional fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) combined with bevacizumab. The primary end point was major morbidity events, defined as surgical resection because of symptoms at or death related to the IPT. A 25% major morbidity rate was considered acceptable. Secondary end points included overall survival (OS) and minor morbidity related to IPT requiring hospitalization, transfusion, or nonsurgical intervention. RESULTS Ninety patients registered between March 2006 and June 2009: 86 were eligible with follow-up, median age was 58 years, and 52% were female. Median follow-up was 20.7 months. There were 12 patients (14%) with major morbidity related to IPT: 10 required surgery (eight, obstruction; one, perforation; and one, abdominal pain), and two patients died. The 24-month cumulative incidence of major morbidity was 16.3% (95% CI, 7.6% to 25.1%). Eleven IPTs were resected without a morbidity event: eight for attempted cure and three for other reasons. Two patients had minor morbidity events only: one hospitalization and one nonsurgical intervention. Median OS was 19.9 months (95% CI, 15.0 to 27.2 months). CONCLUSION This trial met its primary end point. Combining mFOLFOX6 with bevacizumab did not result in an unacceptable rate of obstruction, perforation, bleeding, or death related to IPT. Survival was not compromised. These patients can be spared initial noncurative resection of their asymptomatic IPT.

Tumor DNA content as a prognostic indicator in squamous cell carcinoma of the head and neck region

Our purpose in this study was to determine whether tumor DNA content is a prognostic factor independent of other standard clinical and histologic parameters in squamous cell carcinoma (SCC) of the head and neck region. Tumor DNA content was determined in 76 patients with primary resectable SCC of the oral cavity, larynx, or pharynx who were treated from 1978 to 1984 at the City of Hope. In addition, we measured various clinical and pathologic parameters in all patients. In comparison to patients with diploid SCC, those with aneuploid SCC had significantly decreased relapse-free and overall survival rates (p less than 0.001 for both). A Cox regression analysis demonstrated that tumor DNA content was a prognostic factor independent of all clinicopathologic features examined. By regression analysis, it was the single most important prognostic factor in determining relapse and death from SCC (p less than 0.001 for both).

FXR Regulates Liver Repair after CCl4-Induced Toxic Injury

Liver repair is key to resuming homeostasis and preventing fibrogenesis as well as other liver diseases. Farnesoid X receptor (FXR, NR1H4) is an emerging liver metabolic regulator and cell protector. Here we show that FXR is essential to promote liver repair after carbon tetrachloride (CCl(4))-induced injury. Expression of hepatic FXR in wild-type mice was strongly suppressed by CCl(4) treatment, and bile acid homeostasis was disrupted. Liver injury was induced in both wild-type and FXR(-/-) mice by CCl(4), but FXR(-/-) mice had more severe defects in liver repair than wild-type mice. FXR(-/-) livers had a decreased peak of regenerative DNA synthesis and reduced induction of genes involved in liver regeneration. Moreover, FXR(-/-) mice displayed increased mortality and enhanced hepatocyte deaths. During the early stages of liver repair after CCl(4) treatment, we observed overproduction of TNFalpha and a strong decrease of phosphorylation and DNA-binding activity of signal transducer and activator of transcription 3 in livers from FXR(-/-) mice. Exogenous expression of a constitutively active signal transducer and activator of transcription 3 protein in FXR(-/-) liver effectively reduced hepatocyte death and liver injury after CCl(4) treatment. These results suggest that FXR is required to regulate normal liver repair by promoting regeneration and preventing cell death.

Indications and use of palliative surgery-results of society of surgical oncology survey

Background: Despite increasing attention to end-of-life care in oncology, palliative surgery (PS) remains poorly defined. A survey to test the definition, assess the extent of use, and evaluate attitudes and goals of surgeons regarding PS was devised.Methods: A survey of Society of Surgical Oncology (SSO) members.Results: 419 SSO members completed a 110-item survey. Surgeons estimated 21% of their cancer surgeries as palliative in nature. Forty-three percent of respondents felt PS was best defined based on pre-operative intent, 27% based on post-operative factors, and 30% on patient prognosis. Only 43% considered estimated patient survival time an important factor in defining PS, and 22% considered 5-year survival rate important. The vast majority (95%) considered tumor still evident following surgery in a patient with poor prognosis constituted PS. Most surgeons felt PS could be procedures due to generalized illness related to cancer (80%) or related to cancer treatment complications (76%). Patient symptom relief and pain relief were identified as the two most important goals in PS, with increased survival the least important.Conclusion: PS is a major portion of surgical oncology practice. Quality-of-life parameters, not patient survival, were identified as the most important goals of PS.

Evidence-Based Gallbladder Cancer Staging: Changing Cancer Staging by Analysis of Data From the National Cancer Database

Background:A recent revision of the American Joint Committee on Cancer (AJCC) staging for gallbladder cancer (6th Edition) involved some major changes. Most notably, T2N0M0 tumors were moved from stage II to stage IB; T3N1M0 disease was moved from stage III to stage IIB; and T4NxM0 (x = any) tumors were moved from stage IVA to stage III. Methods:In order to determine if these changes were justified by data, an analysis of the 10,705 cases of gallbladder cancer collected between 1989 and 1996 in the NCDB was performed. All patients had >5 year follow-up. Results:The staging according to the 6th Edition provided no discrimination between stage III and IV. Five-year survivals for stage IIA, IIB, III, and IV (6th Edition) were 7%, 9%, 3%, 2% respectively. The data from the National Cancer Database (NCDB) were used to derive a proposed new staging system that builds upon Edition 5 and had improved discrimination of stage groups over previous editions. Conclusions:Changes in staging systems should be justified by data. Multicenter databases, including the NCDB, represent important resources for verification of evidence-based staging systems.

A prospective evaluation of palliative outcomes for surgery of advanced malignancies.

Background: We prospectively evaluated the effectiveness of major surgery in treating symptoms of advanced malignancies.Methods: Fifty-nine patients were evaluated for major symptoms of intent to treat and were followed up until death or last clinical evaluation. Surgeons identified planned operations before surgery as either curative or palliative and estimated patient survival time. An independent observer assessed symptom relief. A palliative surgery outcome score was determined for each symptomatic patient.Results: Surgeons identified 22 operations (37%) as palliative intent and 37 (63%) as curative intent. The median overall survival time was 14.9 months and did not differ between curative and palliative operations. Surgical morbidity was high but did not differ between palliative (41%) and curative (44%) operations. Thirty-three patients (56%) were symptomatic before surgery, and major symptom resolution was achieved after surgery in 26 (79%) of 33. Good to excellent palliation, defined as a palliative surgery outcome score >70, was achieved in 64% of symptomatic patients.Conclusions: Most symptomatic patients with advanced malignancies undergoing major operations attained good to excellent symptom relief. Outcome measurements other than survival are feasible and can better define the role of surgery in multimodality palliative care. A new outcome measure to evaluate major palliative operations is proposed.

Surgical management of thyroid cancer invading the airway.

AbstractBackground: Locally advanced thyroid cancer invading the tracheal cartilage represents a difficult treatment dilemma during thyroidectomy. Methods: A retrospective chart review was performed to determine the results of laryngotracheal resection or tracheal cartilage shave with adjuvant radiotherapy in patients with locally advanced thyroid cancer invading the upper airway. Results: Of 597 patients undergoing thyroidectomy for thyroid cancer, 40 were found to have laryngotracheal invasion. Thirty-five patients with superficial invasion underwent cartilage shave procedures with adjuvant radiotherapy; five with full-thickness invasion underwent radical resection, including tracheal sleeve resection (n=3) or total laryngectomy (n=2). Histologic subtypes included papillary (n=32), follicular (n=2), Hurthle cell (n=1), medullary (n=3), and anaplastic (n=2). Of the cartilage shave group, 25 are currently alive with no evidence of disease at a mean follow-up of 81 months (range 1–290). Six developed isolated local/regional recurrence and were managed with total laryngectomy (n=1), tracheal resection (n=1), cervical lymphadenectomy (n=1), or repeat radiotherapy (n=3). All six patients remain free of disease at a mean follow-up of 5 years. Of those who underwent initial laryngotracheal resection, four remain free of disease at a mean follow-up of 5 years. The rates of 10-year disease-free survival and overall survival for all patients were 47.9% (95% confidence interval [CI] 24.8, 71.0) and 83.9% (95% CI 70.3, 97.5), respectively. Conclusions: These data suggest that adequate management of thyroid cancer with laryngotracheal invasion can be achieved with a more conservative surgical approach and adjuvant radiotherapy, reserving more radical resections for extensive primary lesions or locally recurrent disease.

Beyond palliative mastectomy in inflammatory breast cancer--a reassessment of margin status.

Background: Inflammatory breast cancer is a locally advanced tumor with an aggressive local and systemic course. Treatment of this disease has been evolving over the last several decades. The aim of this study was to assess whether current therapies, both surgical and chemotherapeutic, are providing better local control (LC) and overall survival (OS). We also attempted to identify clinical and pathologic factors that may be associated with improved OS, disease-free survival (DFS), and LC.Methods: A 25-year retrospective review performed at the City of Hope National Medical Center identified 90 patients with the diagnosis of inflammatory breast cancer.Results: Of the 90 patients identified with inflammatory breast cancer, 33 received neoadjuvant therapy (NEO) consisting of chemotherapy followed by surgery with radiation (n = 26) and without radiation (n = 7). Fifty-seven patients received other therapies (nonNEO). Treatments received by the nonNEO group consisted of chemotherapy, radiation, mastectomy, adrenalectomy, and oophorectomy, alone or in combination. The median follow-up was 28.9 months for the NEO group and 17.6 months for the nonNEO group. Borderline significant differences in the OS distributions between the two groups were found (P =.10), with 3- and 5-year OS for the NEO group of 40.0% and 29.9% and for the nonNEO group of 24.7% and 16.5%, respectively. DFS and LC were comparable in the two groups. Lower stage was associated with an improved OS (P < .05). The 5-year OS for stage IIIB was 30.9%, compared to 7.8% for stage IV. In those patients with stage III disease who were treated with mastectomy and rendered free of disease, margin status was identified by univariate analysis to be a prognostic indicator for OS (P < .05). The 3-year OS, DFS, and LC for patients with negative margins were 47.4%, 37.5%, and 60.3%, respectively, compared to 0%, 16.7%, and 31.3% in patients with positive margins.Conclusions: This study suggests that in patients with inflammatory breast cancer and nonmetastatic disease, an aggressive surgical approach may be justified with the goal of a negative surgical margin. Achievement of this local control is associated with a better overall outcome for this subset of patients. The ability to obtain negative margins may further identify a group of patients with a less aggressive tumor biology that may be more responsive to other modalities of therapy.

Distress and quality of life concerns of family caregivers of patients undergoing palliative surgery.

There has been limited research in the field of palliative care and even far less focus on the area of palliative surgery. Although patient needs are paramount, family caregivers require information and support at the time surrounding surgery for advanced disease. The aim of this prospective cohort study of family caregivers of patients with advanced malignancies was to measure the impact of palliative surgery on dimensions of quality of life (QOL) for these family members. Family caregivers completed assessment tools preoperatively and at approximately 3 weeks and 2 and 3 months postoperatively. Parameters of physical, psychological, social, and spiritual QOL were measured on a scale of 0 (poor) to 10 (good) using the City of Hope QOL-Family instrument. Caregivers recorded their general distress on the Distress Thermometer using a scale of 0 (none) to 10 (severe). Analysis of the data revealed that family caregivers had disruptions similar to patients in physical, psychological, social, and spiritual dimensions of QOL. Findings suggest that caregivers should be assessed for distress and QOL concerns both before and after surgery for patients with advanced malignancies. Although caregiver concerns cannot always be eradicated, resources and interventions to support family caregivers are vital to improving QOL.