High-Risk Nonmelanoma Skin Cancers: Identification, Management, and Reconstruction

2020 ◽  
Vol 36 (02) ◽  
pp. 141-147
Author(s):  
Emily S. Misch ◽  
Adam M. Terella

AbstractHigh-risk nonmelanoma skin cancers of the head and neck may be identified through a variety of tumor risk factors, including location on the lips or ears, size > 2 cm, recurrence, patient immunocompromised status, poor tumor differentiation, > 6 mm thickness, Clark level V depth of invasion, and presence of perineural spread. Surgical excision is the mainstay of treatment, with Mohs' micrographic surgery typically preferred to standard surgical excision. When reconstructing these defects, ensuring negative margins is of utmost importance and delaying reconstruction until confirmation of margins is recommended. Attention to the impact of immunosuppression and adjunct radiation therapy on wound healing is important for an optimal cosmetic outcome. As with all high-risk cancer patients, close follow-up and surveillance of these patients is imperative.

2007 ◽  
Vol 2007 ◽  
pp. 1-6 ◽  
Author(s):  
Michael J. Veness

Nonmelanoma skin cancers (squamous cell and basal cell carcinomas) occur at an epidemic rate in many countries with the worldwide incidence increasing. The sun-exposed head and neck are the most frequent sites for these cancers to arise and in most patients diagnosed with a cutaneous squamous cell carcinoma, local treatment is usually curative. However, a subset is diagnosed with a high-risk cutaneous squamous cell carcinoma. High-risk factors include size (> 2 cm), thickness/depth of invasion (> 4 mm), recurrent lesions, the presence of perineural invasion, location near the parotid gland, and immunosuppression. These patients have a higher risk (> 10–20%) of developing metastases to regional lymph nodes (often parotid nodes), and in some cases also of experiencing local morbidity (perineural invasion), based on unfavourable primary lesion and patient factors. Despite treatment, many patients developing metastatic cutaneous squamous cell carcinoma experience mortality and morbidity usually as a consequence of uncontrolled metastatic nodal disease. It is therefore important that clinicians treating nonmelanoma skin cancers have an understanding and awareness of these high-risk patients. The aim of this article is to discuss the factors that define a high-risk patient and to present some of the issues pertinent to their management.


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Vida V. Bliokas ◽  
Alex R. Hains ◽  
Jonathan A. Allan ◽  
Luise Lago ◽  
Rebecca Sng

Abstract Background Suicide is a major public health issue worldwide. Those who have made a recent suicide attempt are at high risk for dying by suicide in the future, particularly during the period immediately following departure from a hospital emergency department. As such the transition from hospital-based care to the community is an important area of focus in the attempt to reduce suicide rates. There is a need for evaluation studies to test the effectiveness of interventions directed to this stage (termed ‘aftercare’ interventions). Methods A controlled non-randomised two group (intervention vs treatment-as-usual control) design, using an intention-to-treat model, will evaluate the effectiveness of a suicide prevention aftercare intervention providing follow-up after presentations to a hospital emergency department as a result of a suicide attempt or high risk for suicide. The intervention is a community-based service, utilising two meetings with a mental health clinician and follow-up contacts by peer workers via a combination of face-to-face and telephone for four weeks, with the option of extension to 12 weeks. Seventy-five participants of the intervention service will be recruited to the study and compared to 1265 treatment-as-usual controls. The primary hypotheses are that over 12 months, those who participate in the aftercare follow-up intervention are less likely than controls to present to a hospital emergency department for a repeat suicide attempt or because of high risk for suicide, will have fewer re-presentations during this period and will have lower all-cause mortality. As a secondary aim, the impact of the intervention on suicide risk factors for those who participate in the service will be evaluated using pre- and post-intervention repeated measures of depression, anxiety, stress, hopelessness, belongingness, burdensomeness, and psychological distress. Enrolments into the study commenced on 1 November 2017 and are anticipated to cease in November 2019. Discussion The study aims to contribute to the understanding of effective interventions for individuals who have presented to a hospital emergency department as a result of a suicide attempt or at high risk for suicide and provide evidence in relation to interventions that incorporate peer-workers. Trial registration ACTRN12618001701213. Registered on 16 October 2018. Retrospectively registered.


Breast Cancer ◽  
2019 ◽  
Vol 27 (3) ◽  
pp. 405-414
Author(s):  
Satoko Okamoto ◽  
Shu-Tian Chen ◽  
James D. Covelli ◽  
Wendy B. DeMartini ◽  
Bruce L. Daniel ◽  
...  

2016 ◽  
Vol 82 (10) ◽  
pp. 1009-1013 ◽  
Author(s):  
Maris S. Jones ◽  
Hitoe Torisu-Itakura ◽  
Devin C. Flaherty ◽  
Hans F. Schoellhammer ◽  
Jihey Lee ◽  
...  

The impact on survival of a second primary melanoma (SPM) is unclear. We used our melanoma center's database to examine clinicopathologic risk factors and outcomes of stage 0 to IV cutaneous melanoma in patients with one versus two primaries. Among 12,325 patients with primary melanoma, 969 (7.86%) developed SPM. SPMs were significantly thinner than autologous primary melanomas ( P = 0.01), and 451 SPM patients had better overall and melanoma-specific survival than 451 prognostically matched non-SPM patients ( P < 0.0001 and 0.0001, respectively) at a median follow-up of 142.37 months. Patients with cutaneous melanoma are at high risk for development of SPM, but the development of SPM does not seem to impair survival.


2020 ◽  
Vol 38 (33) ◽  
pp. 3925-3936 ◽  
Author(s):  
Alexander M. M. Eggermont ◽  
Christian U. Blank ◽  
Mario Mandala ◽  
Georgina V. Long ◽  
Victoria G. Atkinson ◽  
...  

PURPOSE We conducted the phase III double-blind European Organisation for Research and Treatment of Cancer (EORTC) 1325/KEYNOTE-054 trial to evaluate pembrolizumab versus placebo in patients with resected high-risk stage III melanoma. On the basis of 351 recurrence-free survival (RFS) events at a 1.25-year median follow-up, pembrolizumab prolonged RFS (hazard ratio [HR], 0.57; P < .0001) compared with placebo. This led to the approval of pembrolizumab adjuvant treatment by the European Medicines Agency and US Food and Drug Administration. Here, we report an updated RFS analysis at the 3.05-year median follow-up. PATIENTS AND METHODS A total of 1,019 patients with complete lymph node dissection of American Joint Committee on Cancer Staging Manual (seventh edition; AJCC-7), stage IIIA (at least one lymph node metastasis > 1 mm), IIIB, or IIIC (without in-transit metastasis) cutaneous melanoma were randomly assigned to receive pembrolizumab at a flat dose of 200 mg (n = 514) or placebo (n = 505) every 3 weeks for 1 year or until disease recurrence or unacceptable toxicity. The two coprimary end points were RFS in the overall population and in those with programmed death-ligand 1 (PD-L1)–positive tumors. RESULTS Pembrolizumab (190 RFS events) compared with placebo (283 RFS events) resulted in prolonged RFS in the overall population (3-year RFS rate, 63.7% v 44.1% for pembrolizumab v placebo, respectively; HR, 0.56; 95% CI, 0.47 to 0.68) and in the PD-L1–positive tumor subgroup (HR, 0.57; 99% CI, 0.43 to 0.74). The impact of pembrolizumab on RFS was similar in subgroups, in particular according to AJCC-7 and AJCC-8 staging, and BRAF mutation status (HR, 0.51 [99% CI, 0.36 to 0.73] v 0.66 [99% CI, 0.46 to 0.95] for V600E/K v wild type). CONCLUSION In resected high-risk stage III melanoma, pembrolizumab adjuvant therapy provided a sustained and clinically meaningful improvement in RFS at 3-year median follow-up. This improvement was consistent across subgroups.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 95-95 ◽  
Author(s):  
Prashant Kapoor ◽  
Shaji Kumar ◽  
Rafael Fonseca ◽  
Martha Q. Lacy ◽  
Thomas E Witzig ◽  
...  

Abstract Background: Multiple myeloma (MM) is a heterogeneous disease with very divergent outcomes that are dictated in a large part by specific cytogenetic abnormalities, as well as other prognostic factors such as the proliferative rate of marrow plasma cells. Prognostic systems incorporating these factors have shown clinical utility in identifying high-risk patients, and are increasingly being utilized for treatment decision-making. However, the prognostic relevance of these factors may change with the application of novel therapies. The objective of this study was to determine the impact of risk-stratification (incorporating plasma cell metaphase cytogenetics, interphase fluorescent in-situ hybridization (FISH) and the slide-based plasma cell labeling index (PCLI)) in a cohort of patients with newly diagnosed MM treated initially with lenalidomide + dexamethasone (Rev-Dex). Methods: From March 2004 to November 2007, 100 consecutive patients treated with Rev (25mg/day) on days 1 through 21 of a 4-week cycle in combination with dexamethasone as initial therapy for newly diagnosed myeloma, were identified. High-risk MM was defined as presence of any one or more of the following: hypodiploidy, monoallelic loss of chromosome 13 or its long arm (by metaphase cytogenetics only), deletion of p53 (locus 17p13) or PCLI ≥ 3% or immunoglobulin heavy chain (IgH) translocations, t(4;14) (p16.3;q32) or t(14;16)(q32;q23) on FISH. PFS and OS survival estimates were created using the Kaplan Meier method, and compared by log-rank tests. Results: The median estimated follow-up of the entire cohort (N=100) was 36 months. The median PFS was 31 months; the median OS has not been reached. The 2- and 3-year OS estimates were 93% and 83%, respectively. 16% patients were deemed high-risk by at least one of the 3 tests (cytogenetics, FISH or PCLI). Response rates (PR or better) were 81% versus 89% in the high-risk and standard risk groups, respectively, P=NS; corresponding values for CR plus VGPR rates were 38% and 45% respectively. The median PFS was 18.5 months in high-risk patients compared to 37 months in the standard-risk patients (n=84), P<0.001(Figure). Corresponding values for TTP were 18.5 months and 36.5 months, respectively, P=<0.001. OS was not statistically significant between the two groups; 92% 2-year OS was noted in both the groups. Overall, 95 patients had at least one of the 3 tests to determine risk, while 55 patients could be adequately stratified based on the availability of all the 3 tests, or at least one test result that led to their inclusion in the high-risk category. The significant difference in PFS persisted even when the analysis was restricted to the 55 patients classified using this stringent criterion; 18.5 months vs. 36.5 months in the high-risk and standard- risk groups respectively; P<0.001. In a separate analysis, patients who underwent SCT before the disease progression were censored on the date of SCT to negate its effect, and PFS was still inferior in the high-risk group (p=0.002). Conclusion: The TTP and PFS of high-risk MM patients are inferior to that of the standard-risk patients treated with Rev-Dex, indicating that the current genetic and proliferation-based risk-stratification model remains prognostic with novel therapy. However, the TTP, PFS, and OS obtained in high-risk patients treated with Rev-Dex in this study is comparable to overall results in all myeloma patients reported in recent phase III trials. In addition, no significant impact of high-risk features on OS is apparent so far. Longer follow-up is needed to determine the impact of risk stratification on the OS of patients treated with Rev-Dex. Figure Figure


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2854-2854 ◽  
Author(s):  
Stephan Stilgenbauer ◽  
Florence Cymbalista ◽  
Véronique Leblond ◽  
Alain Delmer ◽  
Dirk Winkler ◽  
...  

Abstract Abstract 2854 Alemtuzumab (A) proved to be efficacious in CLL patients (pts) with very poor prognosis, either due to fludarabine (F) refractoriness or due to unfavorable cytogenetics (17p-). However, rate and duration of remissions still remain unsatisfactory. Therefore, the French and German CLL study groups jointly embarked on this trial, trying to achieve higher overall response rates (ORR) by adding high-dose dexamethasone (D) to A and, simultaneously, investigating the consolidation effect of prolonged A maintenance or allogeneic stem-cell transplantation (allo-SCT), respectively. Induction treatment consisted of subcutaneous A 30 mg weekly × 3 for 28 days, combined with oral D 40 mg on days 1–4 and 15–18, and prophylactic pegfilgrastim 6 mg on days 1 and 15. Depending on the remission status, pts were treated for up to 12 weeks. If CR was documented at 4 or 8 weeks, or at least SD was achieved at 12 weeks, consolidation was scheduled with either allo-SCT or A maintenance with 30 mg every 14 days for up to 2 years (y), at the discretion of pt and physician. Between January 2008 and July 2011, 124 pts were recruited at 26 centers, 120 of whom were eligible. Pts were generally subdivided into three cohorts: 55 pts were refractory (i.e. no response or relapse within 6 months) to regimens containing F or a similar drug (i.e. pentostatin, cladribine, bendamustine). Non-refractory pts all exhibited 17p- and had either untreated (n=39) or relapsed CLL (n = 26) requiring therapy. The median age was high with 66/64/66 y in 17p- 1st line, 17p- relapse, and F-refractory pts, respectively. The three cohorts had 46/54/75% Binet C disease, 41/35/27% B symptoms, 38/42/53% reduced performance status (ECOG 1/2), median thymidine kinase levels of 35/49/24 U/L, median ß2MG levels of 3.8/5.5/4.6 mg/L, and IGHV was unmutated in 89/96/87%. In the F-refractory group, 53% exhibited 17p deletion and 22% had 11q deletion. Pretreated patients had received a median of 3 (F-refractory) or 2 prior lines (17p- relapse). 5 pts had previously undergone autologous and 1 pt allo-SCT. Treatment and efficacy data are currently available for 87 pts who completed induction therapy :17p- 1st-line (n=30), 17p- relapse (n=17), and F-refractory (n=40). Of these, 80/53/55% received the full induction of 12 weeks. ORR (best observed status) was generally high with 97/76/70%. CR was achieved in 20/0/5%. After a median follow-up of 11.8 months (mo), median progression-free survival (PFS) was 16.9/10.4/8.4 mo. Deaths are recorded in 13/27/36% of pts, with median overall survival (OS) not yet reached (>24 mo) in the 17p- 1st line group, and 15/12 mo in 17p- relapse/F-refractory pts. Consolidation treatment was performed as maintenance A (median duration 32 weeks, range 2 – 89) in 34%, and allo-SCT in 30%, with a median age of 66 and 61 y in these subgroups. The main reasons for going off-study without consolidation were death due to infection (14%, n=11, of these 6 without response, and 10 in the F-refractory cohort), CLL progression (12%), and other toxicity (5%). Among the 28 pts not receiving consolidation, there were 19 (68%) deaths, 15 of them in the F-refractory cohort. When comparing A maintenance and allo-SCT for consolidation, there were 9 (35%) and 7 (30%) PD events, respectively and there was so far no significant difference in PFS (median 17 mo in both groups) or OS. During induction, grade 3/4 hematotoxicity consisted of anemia in 28%, neutropenia in 47%, and thrombopenia in 44%. Grade 3/4 non-CMV infection occurred in 29% of 17p- 1st-line, 15% of 17p- relapsed, and 56% of F-refractory pts. CMV reactivation was observed in 54/25/40%, without severe sequelae recorded. During A maintenance, grade 3/4 toxicity consisted of neutropenia in 39% pts and thrombopenia in 4% pts with 6 SAEs (ITP, diarrhea, infection, erythema, tachycardia, and thrombosis). Conclusions: The combination of A and D shows high response rates in ultra high-risk CLL, with promising preliminary findings for PFS and OS, despite the high median age of the pts. The results compare favorably to ORR/CR of 68%/5%, and median PFS of 11.3 mo in the 17p- subgroup of the CLL8 study treated with FCR, consisting of younger pts (median 61 y). In F-refractory CLL however, when compared to the preceding CLL2H study with single agent A, the improved initial response by adding dexamethasone does not seem to translate into improved long-term results. More mature follow-up is needed, especially with respect to the impact of allo-SCT. Disclosures: Stilgenbauer: Amgen: Consultancy, Honoraria, Research Funding; Genzyme: Consultancy, Honoraria, Research Funding. Off Label Use: Alemtuzumab in 1st line CLL treatment. Cymbalista:Roche (d) Mundipharma (e) Genzyme (e): Honoraria, Research Funding. Hinke:WiSP (CRO): Employment.


2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 384-384
Author(s):  
C. Guillen-Ponce ◽  
C. Martinez-Sevila ◽  
R. Jover ◽  
R. Perea ◽  
M. Molina-Garrido ◽  
...  

384 Background: Colonoscopy screening reduces the incidence of, and mortality from, colorectal cancer (CRC) in individuals with HNPCC. The aim of this study was to determine the impact of colonoscopic follow-up in individuals at high risk of HNPCC, in terms of detection of precursor lesions (adenomas) or cancer. Methods: Between 2005-2008, 163 individuals with HNPCC were advised to undergo regular follow-up colonoscopy. Compliance and results of the scans were evaluated annually and were verified with medical documentation. Results: Of the 125 individuals who underwent at least one colonoscopy during the follow-up period of colonoscopy screening, in 33 subjects (26%) at least one colonic adenoma was detected. The median number of adenomas detected per colonoscopy in individuals with polyps was 2. The number of colonoscopies with polyps did not differ between women and men. However, the number of polyps removed by colonoscopy and the total number of polyps removed during the follow-up period was significantly higher in men (p = 0.005, p = 0.05 bilateral, respectively). 5 individuals (4%) were diagnosed with CRC, one of whom had two synchronous tumors. Of these, four individuals had properly followed the screening recommendations with the recommended frequency. In the case where two synchronous tumors were detected, it was the first colonoscopy screening that had been performed on the individual. None had had cancer previously, they were healthy relatives of an index case. All except one belonged to families that fulfilled the Amsterdam criteria I / II. All the tumors were diagnosed at an early stage, except two, which exhibited positive nodes. Conclusions: Colonoscopy screening is effective in diagnosing colorectal adenomas and cancer in individuals with HNPCC. Men with HNPCC have a greater number of colorectal adenomas. Screening allows the detection of colorectal cancer at an early stages. Funded by a young researcher's grant from the Spanish Society of Medical Oncology 2006. No significant financial relationships to disclose.


2018 ◽  
Vol 36 (6_suppl) ◽  
pp. TPS154-TPS154 ◽  
Author(s):  
Todd Matthew Morgan ◽  
David Christopher Miller ◽  
Rodney Dunn ◽  
Linsell Susan ◽  
Linda Okoth ◽  
...  

TPS154 Background: Approximately 30% of patients will have ≥pT3 disease and/or positive surgical margins at radical prostatectomy (RP), indicating a high risk of local recurrence. While current guidelines recommend consideration of adjuvant radiotherapy (aRT) in this setting, < 10% undergo aRT. The Decipher assay is a novel, tissue-based genomic classifier (GC) developed and validated in the post-RP setting as a predictor of metastasis. Current retrospective evidence suggests that patients with a high GC score may benefit from aRT, while observation may be safe for those with a lower GC score. However, there are no randomized prospective data evaluating the clinical utility of biomarkers in men with adverse features after RP. Here we see to determine the impact of GC test results on adjuvant treatment decisions for high-risk post-RP patients vs. clinical factors alone. Methods: Genomics in Michigan ImpactiNg Observation or Radiation (G-MINOR) is a 4-year (12-month enrollment, 3-year follow-up) prospective, cluster-crossover, unblinded, study of 350 subjects from twelve Urology practices in the Michigan Urological Surgery Improvement Collaborative (MUSIC). MUSIC is a physician-led quality improvement consortium nearly all academic and community urology practices within the state of Michigan. Each clinical center participating in this trial will be randomly assigned to either a Genomic Classifier (GC)-based strategy or control arm for a period of 3 months. Patients in both arms will receive a predicted risk of recurrence based on a validated clinical nomogram, the CAPRA-S score, enabling a head-to-head comparison of the Decipher assay with a freely-available validated prognostic tool. Random assignments will be generated centrally by a study statistician and provided to centers immediately before commencing enrollment in each 3-month period. Each center will have two GC and two UC enrollment periods, maintaining study-wide balance and blinding of assignments in subsequent periods. Patients will be followed for receipt of adjuvant therapy as well as oncologic (recurrence, metastasis, and death) and patient-reported quality of life. Clinical trial information: NCT02783950.


2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 114-114
Author(s):  
Ahmed I. Ghanem ◽  
Remonda M Khalil ◽  
Gehan Abd Elatti Khedr ◽  
Amy Tang ◽  
Amr A. Elsaid ◽  
...  

114 Background: Life expectancy is very essential in deciding treatment options in men with prostate cancer (PCa); however, the impact of comorbidities on outcomes is not well-established. We investigated the influence of Charlson Comorbidity Index (CCI) on survival endpoints in men with localized PCa who were treated with prostate radiotherapy (RT). Methods: Men with intermediate and high risk PCa who were treated with definitive RT between 1/2007 and 12/2012 were included. Groups were created according to their baseline CCI score at diagnosis into no, mild and severe comorbidity (CCI 0, 1 or 2+). The groups were then compared based on patients’ characteristics and prognostic factors. Kaplan-Meier curves and Uni/multivariate analyses (MVA) were used to examine the impact of CCI groups on overall (OS), disease specific (DSS), and biochemical relapse free (BRFS) survival. Results: 257 patients were identified after excluding low risk, metastatic cases and those with inadequate follow up. Median follow-up was 92 months (range: 2-135) and median age was 73 years (range: 48-85). 53% of the cases were black and 67% were of intermediate risk. Median RT dose was 76 Gy and 47% received androgen deprivation therapy. CCI groups 0, 1 and 2+ encompassed 76 (30%), 54 (21%) and 127 (49%) patients, respectively. Groups were generally well-balanced. 10 and 15 years OS was significantly different across CCI groups (76% & 53%, 46% & 31% and 55% & 14%, for CCI-0, 1 and 2+ respectively; p < 0.001). CCI-0 had better DSS than CCI-2+ ( p = 0.03) with no difference for CCI-0 vs 1 ( p = 0.1). BRFS was non-different among CCI groups ( p = 0.99). On MVA, increased CCI was deterministic for OS ( p < 0.001) after adjusting for age, Gleason’s score and T-stage. For DSS, only age and T3 vs T1/2 were independently prognostic ( p < 0.001); whereas CCI-1 vs 0 was only marginal ( p = 0.05). Conclusions: Higher CCI was a significant predictor of shorter OS in intermediate and high-risk PCa. Baseline comorbidities should be taken into consideration during patient counselling for treatment options and in designing prospective trials for men with localized prostate cancer.


Sign in / Sign up

Export Citation Format

Share Document