Blood tests to detect circulating tumor cells (CTC) offer great potential to monitor disease status, gauge prognosis, and guide treatment decisions for patients with cancer. For patients with brain ...tumors, such as aggressive glioblastoma multiforme, CTC assays are needed that do not rely on expression of cancer cell surface biomarkers like epithelial cell adhesion molecules that brain tumors tend to lack. Here, we describe a strategy to detect CTC based on telomerase activity, which is elevated in nearly all tumor cells but not normal cells. This strategy uses an adenoviral detection system that is shown to successfully detect CTC in patients with brain tumors. Clinical data suggest that this assay might assist interpretation of treatment response in patients receiving radiotherapy, for example, to differentiate pseudoprogression from true tumor progression. These results support further development of this assay as a generalized method to detect CTC in patients with cancer.
Examining complete gene knockouts within a viable organism can inform on gene function. We sequenced the exomes of 3222 British adults of Pakistani heritage with high parental relatedness, ...discovering 1111 rare-variant homozygous genotypes with predicted loss of function (knockouts) in 781 genes. We observed 13.7% fewer homozygous knockout genotypes than we expected, implying an average load of 1.6 recessive-lethal-equivalent loss-of-function (LOF) variants per adult. When genetic data were linked to the individuals' lifelong health records, we observed no significant relationship between gene knockouts and clinical consultation or prescription rate. In this data set, we identified a healthy PRDM9-knockout mother and performed phased genome sequencing on her, her child, and control individuals. Our results show that meiotic recombination sites are localized away from PRDM9-dependent hotspots. Thus, natural LOF variants inform on essential genetic loci and demonstrate PRDM9 redundancy in humans.
During the coronavirus disease 2019 (COVID‐19) pandemic, providers and patients must engage in shared decision making regarding the pros and cons of early versus delayed interventions for localized ...skin cancer. Patients at highest risk of COVID‐19 complications are older; are immunosuppressed; and have diabetes, cancer, or cardiopulmonary disease, with multiple comorbidities associated with worse outcomes. Physicians must weigh the patient's risk of COVID‐19 complications in the event of exposure against the risk of worse oncologic outcomes from delaying cancer therapy. Herein, the authors have summarized current data regarding the risk of COVID‐19 complications and mortality based on age and comorbidities and have reviewed the literature assessing how treatment delays affect oncologic outcomes. They also have provided multidisciplinary recommendations regarding the timing of local therapy for early‐stage skin cancers during this pandemic with input from experts at 11 different institutions. For patients with Merkel cell carcinoma, the authors recommend prioritizing treatment, but a short delay can be considered for patients with favorable T1 disease who are at higher risk of COVID‐19 complications. For patients with melanoma, the authors recommend delaying the treatment of patients with T0 to T1 disease for 3 months if there is no macroscopic residual disease at the time of biopsy. Treatment of tumors ≥T2 can be delayed for 3 months if the biopsy margins are negative. For patients with cutaneous squamous cell carcinoma, those with Brigham and Women's Hospital T1 to T2a disease can have their treatment delayed for 2 to 3 months unless there is rapid growth, symptomatic lesions, or the patient is immunocompromised. The treatment of tumors ≥T2b should be prioritized, but a 1‐month to 2‐month delay is unlikely to worsen disease‐specific mortality. For patients with squamous cell carcinoma in situ and basal cell carcinoma, treatment can be deferred for 3 months unless the individual is highly symptomatic.
During the coronavirus disease 2019 (COVID‐19) pandemic, providers must help patients to make informed decisions regarding skin cancer management and assess the risk of potential COVID‐19–associated morbidity and/or mortality versus primary skin cancer morbidity and/or mortality. In this article, the authors summarize current data regarding the risk of COVID‐19 complications and mortality based on age and comorbidities, and review the literature assessing how treatment delays affect oncologic outcomes. They provide multidisciplinary recommendations regarding the timing of local therapy for patients with early‐stage skin cancers.
Tumors can rarely overexpress human chorionic gonadotropin (hCG) resulting in false‐positive pregnancy tests. Here, we report a 44‐year‐old female with a metastatic gastrointestinal stromal tumor ...(GIST) who presented with a positive urine pregnancy test before radiotherapy. Further workup ruled out pregnancy. Following radiotherapy, her metastatic disease progressed and her hCG level continued to rise. To the best of our knowledge, this is the first report of a GIST tumor overexpressing hCG.
IMPORTANCE: Current recommendations regarding the size of local excision (LE) margins for Merkel cell carcinoma (MCC) have not been well established. OBJECTIVE: To assess whether larger clinical LE ...margins and receipt of adjuvant radiotherapy are associated with improvements in overall survival (OS) among patients with localized MCC. DESIGN, SETTING, AND PARTICIPANTS: This large multicenter retrospective cohort study used records from the National Cancer Database to identify adult patients with localized stage I or stage II MCC who underwent LE between January 1, 2004, and December 31, 2015. Data were analyzed from August 1, 2020, to January 25, 2021. EXPOSURES: Local excision margin size and adjuvant radiotherapy. MAIN OUTCOMES AND MEASURES: Overall and net survival were assessed using Cox multivariable regression analysis. RESULTS: A total of 6156 patients with localized MCC (median age at diagnosis, 77 years range, 27-90 years; 2500 women 40.6%). In the multivariable regression analysis, LE clinical margins larger than 1.0 cm were associated with improvements in OS (HR, 0.88; 95% CI, 0.81-0.95; P < .001) compared with margins of 1.0 cm or smaller, regardless of tumor subsite. At 5 years after surgery, LE margins of 1.0 cm or smaller were associated with a net survival of 76.7%, while LE margins larger than 1.0 cm were associated with a net survival of 89.8% (P < .001). Stratification of LE margins into 3 subgroups indicated that LE margins of 1.1 to 2.0 cm (HR, 0.87; 95% CI, 0.76-0.99; P = .047) and larger than 2.0 cm (HR, 0.84; 95% CI, 0.72-0.98; P = .03) were associated with improvements in OS compared with margins of 1.0 cm or smaller. In patients with less aggressive disease (ie, those who were immunocompetent and had tumors ≤1.0 cm, no lymphovascular invasion, and negative pathologic margins), LE margins larger than 1.0 cm were also associated with improvements in OS (HR, 0.87; 95% CI, 0.78-0.97; P = .01). Among patients who received adjuvant radiotherapy, larger LE margins were associated with improvements in OS (HR, 0.87; 95% CI, 0.76-0.98; P = .03). Receipt of adjuvant radiotherapy was also associated with improvements in OS within the 3 LE margin subgroups. Patients who received adjuvant radiotherapy and had LE margins of 1.0 cm or smaller (HR, 0.81; 95% CI, 0.74-0.89; P < .001) experienced OS that was comparable to that in patients who did not receive adjuvant radiotherapy and had LE margins larger than 1.0 cm (HR, 0.80; 95% CI, 0.71-0.89; P = .87). CONCLUSIONS AND RELEVANCE: In this study, LE clinical margins larger than 1.0 cm were associated with improvements in OS, and these improvements were independent of tumor subsite, receipt of adjuvant radiotherapy, positive pathologic margins, or adverse pathologic features for stage I to stage II MCC. Patients with LE margins of 1.0 cm or smaller who received adjuvant radiotherapy experienced OS that was similar to that of patients with larger LE margins who did not receive radiotherapy. The combination of LE clinical margins larger than 1.0 cm and adjuvant radiotherapy was associated with the highest OS.
Folliculotropic mycosis fungoides is a variant of cutaneous T-cell lymphoma characterized as having a folliculocentric infiltrate of malignant T-cells along with a worse prognosis in comparison to ...the epidermotropic variants. Patients with advanced forms of folliculotropic mycosis fungoides are often poorly responsive to both skin-directed as well as to systemic therapies. We report here a high response rate using a novel therapeutic regimen combining interferon gamma, isotretinoin in low dose and topical carmustine, and in some cases concomitant skin-directed therapies, among 6 consecutive patients with refractory folliculotropic mycosis fungoides with stages IB through IIIB who had previously failed both topical and systemic therapies. The potential mechanisms of this multimodality approach are discussed.
BACKGROUNDThe American Society of Dermatologic Surgery (ASDS) is the major educational organization for dermatologic surgery in the United States. Presidents are elected annually from among their ...members.
OBJECTIVEThe authors investigated the demographics, training, and achievements of the ASDS presidents.
MATERIALS AND METHODSAll ASDS presidents (1970–2017) were included. Data were gathered using publicly available information from websites, curriculum vitae, and PubMed. Living presidents were contacted by email (if available) to verify the collected data.
RESULTSOf 46 ASDS presidents, 87% are male, with the first female president elected in 1994. Fifty-nine percent are members of the American College of Mohs Surgery. Seven presidents received dual fellowship training. Four presidents received a second graduate degree. Mean duration from residency to presidency was 22 years, with the mean age being 53 years. PubMed publication average was 34. All presidents have been affiliated with academic institutions, with 26% appointed as department chair and 30% serving as academic dermatologic surgery director.
CONCLUSIONThe authors report that most of the ASDS presidents have been male with over half receiving Mohs surgery fellowship training. All have had academic affiliations at some point in their careers, with some named department chairs and/or elected as presidents of other national dermatologic societies.
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