Eli Avisar

Clinicopathologic Predictors of Sentinel Lymph Node Metastasis in Thin Melanoma

PURPOSE Indications for sentinel lymph node biopsy (SLNB) for thin melanoma are continually evolving. We present a large multi-institutional study to determine factors predictive of sentinel lymph node (SLN) metastasis in thin melanoma. PATIENTS AND METHODS Retrospective review of the Sentinel Lymph Node Working Group database from 1994 to 2012 identified 1,250 patients who had an SLNB and thin melanomas (≤ 1 mm). Clinicopathologic characteristics were correlated with SLN status and outcome. RESULTS SLN metastases were detected in 65 (5.2%) of 1,250 patients. On univariable analysis, rates of Breslow thickness ≥ 0.75 mm, Clark level ≥ IV, ulceration, and absence of regression differed significantly between positive and negative SLN groups (all P < .05). These four variables and mitotic rate were used in multivariable analysis, which demonstrated that Breslow thickness ≥ 0.75 mm (P = .03), Clark level ≥ IV (P = .05), and ulceration (P = .01) significantly predicted SLN metastasis with 6.3%, 7.0%, and 11.6% of the patients with these respective characteristics having SLN disease. Melanomas < 0.75 mm had positive SLN rates of < 5% regardless of Clark level and ulceration status. Median follow-up was 2.6 years. Melanoma-specific survival was significantly worse for patients with positive versus negative SLNs (P = .001). CONCLUSION Breslow thickness ≥ 0.75 mm, Clark level ≥ IV, and ulceration significantly predict SLN disease in thin melanoma. Most SLN metastases (86.2%) occur in melanomas ≥ 0.75 mm, with 6.3% of these patients having SLN disease, whereas in melanomas < 0.75 mm, SLN metastasis rates are < 5%. By using a 5% metastasis risk threshold, SLNB is indicated for melanomas ≥ 0.75 mm, but further study is needed to define indications for SLNB in melanomas < 0.75 mm.

Stress Management Intervention Reduces Serum Cortisol and Increases Relaxation During Treatment for Nonmetastatic Breast Cancer

Objective: To examine the effects of a cognitive-behavioral stress management (CBSM) intervention, which was composed of relaxation, cognitive restructuring, and coping skills training on late afternoon serum cortisol and relaxation indicators in women who were undergoing treatment for nonmetastatic breast cancer. Methods: Participants (N = 128) were randomly assigned to receive a 10-week CBSM group intervention or a 1-day psychoeducation seminar. Serum cortisol was collected and ability to relax was assessed at study entry and again at 6- and 12-month follow-up visits. Data were analyzed using latent growth curve modeling. Results: There was a significant effect of study condition on change across time for both cortisol and perceived ability to relax. Women receiving CBSM had significantly greater reductions in cortisol levels across the 12 months compared with those in the control group, who had no appreciable decline. Women receiving CBSM reported greater increases in ability to relax than controls across time. Perceived ability to relax did not mediate CBSM-related reductions in cortisol. Conclusions: Women who participate in a 10-week CBSM intervention during treatment for breast cancer show decreases in physiological stress in parallel with increases in perceived relaxation skills. This is the first study demonstrating well-maintained reductions in cortisol after a CBSM intervention in cancer patients during and just after treatment. CBSM = cognitive-behavioral stress management; MOCS = Measure of Current Status; MOCSrelax = relaxation subscale of the MOCS; LGM = latent growth curve modeling; HPA = hypothalamic-pituitary-adrenal.

Angiosarcomas of the breast: a review of 70 cases.

Objective:Angiosarcoma arising in the irradiated breast after breast-conserving therapy is being reported with increasing frequency. As more women undergo breast-conserving therapy, the incidence can be expected to increase. The objective of this study was to review breast angiosarcomas diagnosed from 1981 to 2000 from our state cancer registry. Methods:A comprehensive review of a population-based registry, Florida Cancer Data System, identified 70 cases of breast angiosarcomas from 1981 to 2000. Descriptive statistical and &khgr;2 analyses were performed. Results:Of the 70 cases at presentation, 39 were primary breast angiosarcomas (PBAs) and 31 were secondary breast angiosarcomas (SBAs). The mean ages were 59 and 72.9 for the PBA and SBA groups, respectively. In the SBA group the mean age of breast cancer diagnosis was 67.6. The mean time to diagnosis of the angiosarcoma was 5.2 years after breast cancer irradiation. At presentation 82% (n = 32) and 48% (n = 15), in the PBA and SBA groups, respectively had local disease (P = 0.003). The primary treatment was mastectomy in each group. There was no difference in mortality between the 2 groups (PSA; n = 18, SBA; n = 17). Conclusion:Angiosarcoma of the breast is rare and this study reports a review of 70 cases from 1980 to 2000. Angiosarcoma after breast-conserving therapy is increasingly diagnosed in a small but significant portion of breast carcinoma survivors. SBA patients present with more advance disease. Surgical resection is the primary therapy. The aggressive nature of this disease demands further investigation of adjuvant therapy to prevent recurrence of disease after surgery.

Novel IL-21 signaling pathway up-regulates c-Myc and induces apoptosis of diffuse large B-cell lymphomas

Interleukin-21 (IL-21), a member of the IL-2 cytokine family, has diverse regulatory effects on natural killer (NK), T, and B cells. In contrast to other cytokines that are usually immunostimulatory, IL-21 can induce apoptosis of murine B cells at specific activation-differentiation stages. This effect may be used for treatment of B-cell malignancies. Herein we report that diffuse large B-cell lymphoma (DLBCL) cell lines exhibit widespread expression of the IL-21 receptor (IL-21R) and that IL-21 stimulation leads to cell-cycle arrest and caspase-dependent apoptosis. IL-21 also induces apoptosis in de novo DLBCL primary tumors but does not affect viability of human healthy B cells. Furthermore, IL-21 promotes tumor regression and prolongs survival of mice harboring xenograft DLBCL tumors. The antilymphoma effects of this cytokine are dependent on a mechanism involving IL-21-activated signal transducer and activator of transcription 3 (STAT3) up-regulating expression of c-Myc. This up-regulation promotes a decrease in expression of antiapoptotic Bcl-2 and Bcl-X(L) proteins triggering cell death. Our results represent one of the first examples in which the STAT3-c-Myc signaling pathway, which can promote survival and oncogenesis, can induce apoptosis in neoplastic cells. Moreover, based on IL-21s potency in vitro and in animal models, our findings indicate that this cytokine should be examined in clinical studies of DLBCL.

Results of 23,810 Cases of Ductal Carcinoma-in-situ

BackgroundScreening mammography has increased the number of patients diagnosed with ductal carcinoma-in-situ (DCIS) in the past 20 years. The Florida Cancer Data System is the largest single source incident cancer registry in the United States. We analyzed this registry to determine the changing incidence and treatment patterns for DCIS.MethodsPatients with DCIS from 1981 to 2001 were identified. Age-adjusted rate, descriptive statistics, and incidence of future DCIS and invasive breast cancer were calculated.ResultsA total of 23,810 DCIS patients were identified. The age-adjusted rate of DCIS has risen from 2.4 to 27.7 per 100,000 women between 1981 and 2001. Median age was 64 years; 85% of patients were white, 6.6% African American, and 7.5% Hispanic. Median tumor size was .9 cm. Forty-seven percent of patients had breast-conserving therapy (BCT). Half of the 53% of patients undergoing mastectomy underwent a modified radical mastectomy. Eight percent received no surgical treatment. Sentinel lymph node biopsy was used in 2.7% of patients who underwent a mastectomy. After BCT, 37.5% received adjuvant radiotherapy, and only 13% were treated with hormonal therapy.ConclusionsThe incidence of DCIS has risen dramatically with the advent of screening mammography. Increasing numbers of these patients are treated with BCT, although a large proportion are still treated with mastectomy, in some cases combined with axillary dissection. Sentinel lymph node biopsy and tamoxifen are important components of therapy, the use of which is slowly increasing in the treatment of DCIS.

Factors predictive of the status of sentinel lymph nodes in melanoma patients from a large multicenter database.

BackgroundNumerous predictive factors for cutaneous melanoma metastases to sentinel lymph nodes have been identified; however, few have been found to be reproducibly significant. This study investigated the significance of factors for predicting regional nodal disease in cutaneous melanoma using a large multicenter database.MethodsSeventeen institutions submitted retrospective and prospective data on 3463 patients undergoing sentinel lymph node (SLN) biopsy for primary melanoma. Multiple demographic and tumor factors were analyzed for correlation with a positive SLN. Univariate and multivariate statistical analyses were performed.ResultsOf 3445 analyzable patients, 561 (16.3%) had a positive SLN biopsy. In multivariate analysis of 1526 patients with complete records for 10 variables, increasing Breslow thickness, lymphovascular invasion, ulceration, younger age, the absence of regression, and tumor location on the trunk were statistically significant predictors of a positive SLN.ConclusionsThese results confirm the predictive significance of the well-established variables of Breslow thickness, ulceration, age, and location, as well as consistently reported but less well-established variables such as lymphovascular invasion. In addition, the presence of regression was associated with a lower likelihood of a positive SLN. Consideration of multiple tumor parameters should influence the decision for SLN biopsy and the estimation of nodal metastatic disease risk.

Lumpectomy and Breast Irradiation for Breast Cancer Arising After Previous Radiotherapy for Hodgkin’s Disease or Lymphoma

Twelve women treated with radiotherapy with or without chemotherapy for Hodgkin’s disease (11 patients) and non-Hodgkin’s lymphoma (1 patient) and in whom breast cancer subsequently developed 10 to 29 years later were treated with lumpectomy and breast irradiation, 5,000 cGy/25–30 fractions to the whole breast and 900 cGy to 1,000 cGy/5 boost to the operative area. Six also received adjuvant chemotherapy for breast cancer. Breast irradiation was well tolerated without any unusual acute or chronic sequelae. All women had a good to excellent cosmetic result. Ten women are alive and well 1 to 174 months (median: 46) from completion of breast irradiation. Two women died with distant metastasis but without local recurrence. Breast conservation therapy with radiotherapy is not contraindicated in the woman who has previously been treated with radiotherapy for Hodgkin’s disease or lymphoma.

Adenocarcinoma in a mid-esophageal diverticulum

The incidence of esophageal adenocarcinoma has been increasing compared with squamous cell carcinoma. The most common location of adenocarcinoma of the esophagus is the distal one third. Cancer developing in an esophageal diverticulum is uncommon, but tumors of squamous cell origin in esophageal diverticula have been reported previously. We describe an adenocarcinoma in a midesophageal diverticulum and review malignancies occurring in esophageal diverticula.

Internal mammary sentinel node biopsy for breast cancer

BACKGROUND The purpose of this study was to determine the value of lymphoscintigraphy (LS) for internal mammary sentinel node (IMSN) identification, the metastatic rate, and the change in staging and treatment. METHODS Between 2001 and 2007 a prospective database was obtained of all patients undergoing IMSN biopsies using an open or thoracoscopic approach. Radiotracer injection was peritumoral. RESULTS Thirty-four patients were included. There was one man. Three had ductal carcinoma in situ. LS showed IMSN in 47.1%. The IMSN biopsy success rate was 91.2%. Seven of the 28 successfully biopsied invasive cancer patients had metastatic IMSNs (25%). Positive IMSNs were associated with positive axillary nodes in 71.4% (P = .036). All patients with positive IMSNs were upstaged and received radiation to the internal mammary chain. In 4 of 28 patients (14%) the chemotherapy plans were probably altered. In univariate and multivariate analyses tumor size, location, nuclear grade, estrogen receptors, progesterone receptors, Her-2, and histology were not significant predictors of positivity. CONCLUSIONS IMSNs were positive in 25% of the invasive cancer patients. All had treatment changes. LS identified less than 50% of IMSNs. There are no good tumor-related predictors of IMSN positivity.

Brief cognitive-behavioral and relaxation training interventions for breast cancer: A randomized controlled trial

OBJECTIVE Women with breast cancer (BCa) report elevated distress postsurgery. Group-based cognitive-behavioral stress management (CBSM) following surgery improves psychological adaptation, though its key mechanisms remain speculative. This randomized controlled dismantling trial compared 2 interventions featuring elements thought to drive CBSM effects: a 5-week cognitive-behavioral training (CBT) and 5-week relaxation training (RT) versus a 5-week health education (HE) control group. METHOD Women with stage 0-III BCa (N = 183) were randomized to CBT, RT, or HE condition 2-10 weeks postsurgery. Psychosocial measures were collected at baseline (T1) and postintervention (T2). Repeated-measures analyses of variance (ANOVAs) tested whether CBT and RT treatments improved primary measures of psychological adaptation and secondary measures of stress management resource perceptions from pre- to postintervention relative to HE. RESULTS Both CBT and RT groups reported reduced depressive affect. The CBT group reported improved emotional well-being/quality of life and less cancer-specific thought intrusions. The RT group reported improvements on illness-related social disruption. Regarding stress management resources, the CBT group reported increased reliability of social support networks, while the RT group reported increased confidence in relaxation skills. Psychological adaptation and stress management resource constructs were unchanged in the HE control group. CONCLUSIONS Nonmetastatic breast cancer patients participating in 2 forms of brief, 5-week group-based stress management intervention after surgery showed improvements in psychological adaptation and stress management resources compared with an attention-matched control group. Findings provide preliminary support suggesting that using brief group-based stress management interventions may promote adaptation among nonmetastatic breast cancer patients.