Bruce J. Averbook

Pediatric Melanoma: Analysis of an International Registry

The management of pediatric melanoma (PM) has largely been extrapolated from adult data. However, the behavior of PM appears to differ from its adult counterparts. Therefore, an international PM registry was created and analyzed.

Melanoma in Pediatric, Adolescent, and Young Adult Patients

The family practitioner, pediatrician, and dermatologist all have potential roles in the primary prevention, diagnosis, and treatment of localized thin melanomas. Surgical and medical oncologists are often involved when controversy arises over the nature of the skin lesion or whether sentinel lymph node (SLN) biopsies and adjuvant therapy are to be contemplated. This overview of melanoma will deal with the primary and nodal pathology, surgery, and medical therapy of melanoma in pediatric, adolescent, and young adult patients--and will raise areas of controversy that are only recently being addressed in databases of cases from this age group.

Antitumor effects of Flt3 ligand in transplanted murine tumor models

Administration of Flt3 ligand (FL) to mice causes dendritic and natural killer cells to increase but certain solid tumors to regress. Depending on the particular tumor model used, T cells and natural killer cells have been implicated in the protective immune response induced by FL. The current study examined the effects of FL administration on tumor establishment and progression in metastatic and primary tumor models to correlate anatomic location with immunotherapeutic efficacy. FL mediated significant (p ≤ 0.05) therapeutic activity against pulmonary metastases of the murine MC-38 colon adenocarcinoma, particularly when cytokine administration was initiated before tumor inoculation. However, progressive intraabdominal tumors sometimes were observed even in the relative absence of pulmonary metastases. Significant, although less dramatic, antimetastatic effects were observed with MCA-205 and MCA-102 sarcomas and D5 (B16BL6) melanoma. In contrast, FL was ineffective against subcutaneous MC-38 tumors or against several intracranial tumors. This suggests that besides the administration dose, the efficacy of this cytokine depends on the tumor type and possibly the location of the inoculated tumor. Antitumor activities of FL were abolished by whole-body irradiation (500 cGy) and partially abolished by systemic depletion of CD8, CD4, or natural killer cells. The results indicate that optimization of FL immunotherapy of tumors will require a firmer understanding of the relative contributions of tumor burden, location, immune system requirements, and other factors.

Skin cancer screening: recommendations for data-driven screening guidelines and a review of the US Preventive Services Task Force controversy

Melanoma is usually apparent on the skin and readily detected by trained medical providers using a routine total body skin examination, yet this malignancy is responsible for the majority of skin cancer-related deaths. Currently, there is no national consensus on skin cancer screening in the USA, but dermatologists and primary care providers are routinely confronted with making the decision about when to recommend total body skin examinations and at what interval. The objectives of this paper are: to propose rational, risk-based, data-driven guidelines commensurate with the US Preventive Services Task Force screening guidelines for other disorders; to compare our proposed guidelines to recommendations made by other national and international organizations; and to review the US Preventive Services Task Forces 2016 Draft Recommendation Statement on skin cancer screening.

Coinfusion of irradiated splenocytes with low titer tumor-infiltrating lymphocytes augments antitumor efficacy in adoptive immunotherapy

We hypothesized that adoptively increasing the density of antigen-presenting cells (APCs) at a tumor site would improve tumor-infiltrating lymphocyte (TIL) in vivo antitumor efficacy. Irradiated splenocytes were used as crude APCs. Alone, they did not have in vitro antitumor activity nor did they augment TIL efficacy in vitro. Pulmonary metastases were established by intravenous (i.v.) injection of 5 x 10(5) MC-38 tumor into irradiated C57B1/6 mice (500 cGy). After 3 days, MC-38 TIL (0.1, 0.5, and 1 x 10(6) cells) +/- irradiated splenocytes (5,000 cGy) as APCs were administered intravenously (0.25, 0.5, and 1 x 10(6) cells) to each group (n = 5/group). Interleukin-2 (60,000 IU) was injected intraperitoneally three times daily for 3 days. Mice were sacrificed 9 days later and metastases elaborated in blinded fashion. A titer of 1 x 10(6) TIL, completely eradicated pulmonary metastases. In two consecutive experiments, when increasing titers of irradiated splenocytes were coinfused with a constant titer of TIL that did not completely eradicate pulmonary metastases, a moderate reduction in pulmonary metastases was observed. The contribution of splenocytes to an improvement in TIL antitumor efficacy was not altered when irradiated splenocytes derived from mice bearing 10-day subcutaneous MC-38 tumors were used. The coinfusion of nonirradiated splenocytes did not improve TIL antitumor in vivo activity. Activated B cells (expressing ICAM-1, B7.1, and B7.2) had no effect on in vitro tumor lysis and did not augment in vivo TIL efficacy. The results show a modest but statistically significant improvement in adoptive immunotherapy antitumor efficacy with fewer TIL by coinfusion of irradiated splenocytes. Further studies to characterize the active potential APC cell subpopulation and to clarify the mechanism(s) responsible for in vivo augmentation of TIL antitumor efficacy are in progress.

Staging breast cancer by sentinel lymph node biopsy: Do patients with a single negative sentinel node (N=1) experience worse outcomes than those with multiple negative sentinel nodes (N>1)?

BACKGROUND Though sentinel lymph node biopsy (SLNB) is standard of care for early breast cancer, concern remains for false negative nodes and potential implications for understaging and under-treatment, particularly when only one sentinel node is retrieved. We examined whether patients with a single negative SLN (N = 1) experience worse survival than those with two or more negative SLNs (N > 1). METHODS This retrospective review examined 730 SLN-negative patients. Clinicopathologic and demographic data, recurrence-free and overall survival were assessed. Statistical analysis included Chi square tests, Kaplan-Meier survival analysis with log-rank tests, and multivariate analysis using the Cox regression model. RESULTS There were no statistically significant differences in recurrence-free or overall survival between patients in the N = 1 versus the N > 1 group (log rank test, p = 0.75 and p = 0.52, respectively). There were also no differences in local and distant recurrence (1.9% versus 2.1%, p = 0.89 and 2.4% versus 2.3%, p = 0.78) or breast cancer death (2.4% versus 2.7%, p = 0.85). Increased tumor size was associated with finding greater than one negative sentinel node intraoperatively (p = 0.01). CONCLUSIONS A single negative sentinel node did not portend worse recurrence-free or overall survival. After thorough axillary exploration during SLNB, retrieval of a single negative SLN did not result in worse clinical outcomes.