Adherence with surveillance schedule in patients with invasive melanoma.

BACKGROUND: Seven percent of patients develop melanoma recurrence after successful treatment, and 4-8% develop a second primary melanoma. This study aimed to assess how providing Survivorship Care Plans (SCPs) to patients may improve adherence to surveillance visits. METHODS: All patients treated for invasive melanoma at our institution between 8/1/2018-2/29/2020 were included in this retrospective chart review. SCPs were delivered in-person to patients and sent to primary care providers and dermatologists. Logistic regression was performed to assess influences on adherence. RESULTS: Of 142 patients, 73 (51.4%) received SCP regarding their follow-up care. Reception of SCP (p = 0.044) and shorter distance from clinic (p = 0.018) significantly improved rates of adherence. Seven patients developed melanoma recurrences, five were physician-detected. Three patients had primary site recurrence, six had lymph node recurrences, and three had distant recurrences. There were 5 second primaries, all physician-detected. CONCLUSION: Our study is the first to investigate the impact of SCPs on patient adherence in melanoma survivors and the first to reveal a positive correlation between SCPs and adherence in any type of cancer. Melanoma survivors require close clinical follow-up, as demonstrated by our study finding that even with SCPs, most recurrences and all new primary melanomas were physician-detected.

Sentinel lymph node biopsy in desmoplastic melanoma - the percent desmoplastic component matters: A systematic review.

BACKGROUND: Desmoplastic melanoma (DM) is a less common form of cutaneous melanoma that has been described for decades; however, controversy remains regarding the management and use of sentinel lymph node biopsy (SLNB). The purpose of this study is to identify whether SLNB is indicated in all cases of DM, including the pure subtype. METHODS: A systematic review was conducted using PubMed (with access to MEDLINE) along with the Cochrane Central Register of Controlled Trials from 2001 to 2019. Case series and case-control studies were included. RESULTS: Eighteen studies were included for a total population of 3,914 patients. SLNB was performed in 2229 patients. The percentage of positive SLNB results was 8.5%. However, patients with pure DM (>90% desmoplastic component) were found to have a significantly lower rate of occult metastatic node positivity when compared with that of mixed DM (4.9% and 14.8%, respectively). CONCLUSIONS: Our findings underscore the importance of the pathologist reporting percentage of desmoplastic component in melanoma. SLNB should be strongly considered for patients with mixed DM. However, the low rate of occult metastatic node positivity in pure DM is beneath the threshold for using SLNB as a staging procedure. SUMMARY: Previous studies have suggested that desmoplastic melanoma is less likely to metastasize to regional lymph nodes when compared with conventional melanoma. This review suggests that it is imperative to distinguish the histologic subtype of desmoplastic melanoma to determine if staging procedure is indicated.

Identification of a Subset of Stage I Colorectal Cancer Patients With High Recurrence Risk.

BACKGROUND: A challenge in early-stage colorectal cancer (CRC) is identifying biomarkers that predict an increased risk for recurrence. A potential clinically adaptable biomarker is focal adhesion kinase (FAK), a tyrosine kinase that promotes invasion and metastasis. METHODS: An initial, single-institution, 298-patient cohort with all stages of CRC and long-term follow-up was assessed for FAK with tissue microarrays using immunohistochemistry. FAK expression was scored and dichotomized into high and low. Subsequently, a validation cohort of 517 early-stage CRCs from a separate institution was evaluated. All statistical tests were 2-sided. RESULTS: FAK overexpression did not correlate with any known histologic feature and was an early event in CRC, increasing from normal colon to stage I, and stage I to II, but not different at higher stages. High FAK was associated with decreased 10-year recurrence-free survival (RFS) among stage I patients (70.2% for high FAK vs 94.1% for low, P = .02), but not among higher stages in the initial cohort. The same finding was seen in the validation cohort (73.1% for high FAK vs 93.1% for low, P = .004). Multivariable survival analysis for stage I patients showed only two statistically significant factors predicting RFS: FAK (hazard ratio = 5.27, 95% confidence interval = 1.81 to 15.33, P = .002) and perineural invasion (hazard ratio = 7.38, 95% confidence interval = 1.01 to 53.96, P = .049). FAK was the only statistically significant factor in multivariable analysis across RFS, overall, and disease-specific survivals. CONCLUSIONS: High FAK expression identified a subset of stage I CRC patients with high incidence of recurrence and reduced survival, suggesting that FAK has important prognostic value. These patients would immediately benefit from more rigorous surveillance protocols for recurrent disease.

Neoantigen-Reactive T Cells: The Driving Force behind Successful Melanoma Immunotherapy.

Patients with metastatic cutaneous melanoma have experienced significant clinical responses after checkpoint blockade immunotherapy or adoptive cell therapy. Neoantigens are mutated proteins that arise from tumor-specific mutations. It is hypothesized that the neoantigen recognition by T cells is the critical step for T-cell-mediated anti-tumor responses and subsequent tumor regressions. In addition to describing neoantigens, we review the sentinel and ongoing clinical trials that are helping to shape the current treatments for patients with cutaneous melanoma. We also present the existing evidence that establishes the correlations between neoantigen-reactive T cells and clinical responses in melanoma immunotherapy.

Preoperative leukopenia does not affect outcomes in cancer patients undergoing elective and emergent abdominal surgery: A brief report.

BACKGROUND: Leukopenic patients have historically been considered poor surgical candidates due to a perceived increase in operative morbidity and mortality. METHODS: Retrospective cohort study using the NSQIP database to identify adult patients who received chemotherapy for malignancy within 30-days prior to elective or emergent abdominal surgery between 2008 and 2011. Leukopenia was defined as < 4000 WBC/mm3 within 2-days prior to surgery. Multiple logistic regression assessed if leukopenia was associated with morbidity and mortality. RESULTS: Of the 4369 patients included, 20.2% had preoperative leukopenia. Emergency cases comprised 36.2% of cases. Overall 30-day mortality was 12.2% and 30-day composite morbidity was 29.8%. After controlling for significant confounders, including emergency status, leukopenia was not significantly associated with either postoperative mortality (p = 0.14) or morbidity (p = 0.17). CONCLUSIONS: Our study suggests that in cancer patients undergoing chemotherapy, leukopenia is not associated with morbidity or mortality and should not influence operative planning in either the elective or emergent setting.

Efficient identification of mutated cancer antigens recognized by T cells associated with durable tumor regressions.

PURPOSE: Cancer immunotherapy with adoptive transfer of tumor-infiltrating lymphocytes (TIL) represents an effective treatment for patients with metastatic melanoma, with the objective regressions in up to 72% of patients in three clinical trials. However, the antigen targets recognized by these effective TILs remain largely unclear. EXPERIMENTAL DESIGN: Melanoma patients 2359 and 2591 both experienced durable complete regressions of metastases ongoing beyond five years following adoptive TIL transfer. Two conventional screening approaches were carried out to identify the antigens recognized by these clinically effective TILs. In addition, a novel approach was developed in this study to identify mutated T-cell antigens by screening a tandem minigene library, which comprised nonsynonymous mutation sequences identified by whole-exome sequencing of autologous tumors. RESULTS: Screening of an autologous melanoma cDNA library using a conventional approach led to the identification of previously undescribed nonmutated targets recognized by TIL 2359 or TIL 2591. In contrast, screening of tandem minigene libraries encoding tumor-specific mutations resulted in the identification of mutated kinesin family member 2C (KIF2C) antigen as a target of TIL 2359, and mutated DNA polymerase alpha subunit B (POLA2) antigen as a target of TIL 2591. Both KIF2C and POLA2 have been found to play important roles in cell proliferation. CONCLUSIONS: These findings suggest that the minigene screening approach can facilitate the antigen repertoire analysis of tumor reactive T cells, and lead to the development of new adoptive cell therapies with purified T cells that recognize candidate-mutated antigens derived from genes essential for the carcinogenesis.