Malignancies In Solid Organ Transplant Recipients Research Articles

Updates in Skin Cancer in Transplant Recipients and Immunosuppressed Patients: Review of the 2022-2023 Scientific Symposium of the International Immunosuppression and Transplant Skin Cancer Collaborative.

The International Immunosuppression and Transplant Skin Cancer Collaborative (ITSCC) and its European counterpart, Skin Care in Organ Transplant Patients-Europe (SCOPE) are comprised of physicians, surgeons, and scientist who perform integrative collaborative research focused on cutaneous malignancies that arise in solid organ transplant recipients (SOTR) and patients with other forms of long-term immunosuppression. In October 2022, ITSCC held its biennial 4-day scientific symposium in Essex, Massachusetts. This meeting was attended by members of both ITSCC and SCOPE and consisted of specialists including Mohs micrographic and dermatologic oncology surgeons, medical dermatologists, transplant dermatologists, transplant surgeons, and transplant physicians. During this symposium scientific workshop groups focusing on consensus standards for case reporting of retrospective series for invasive squamous cell carcinoma (SCC), defining immunosuppressed patient status for cohort reporting, development of multi-institutional registry for reporting rare tumors, and development of a KERACON clinical trial of interventions after a SOTRs' first cutaneous SCC were developed. The majority of the symposium focused on presentation of the most up to date research in cutaneous malignancy in SOTR and immunosuppressed patients with specific focus on chemoprevention, immunosuppression regimens, immunotherapy in SOTRs, spatial transcriptomics, and the development of cutaneous tumor registries. Here, we present a summary of the most impactful scientific updates presented at the 2022 ITSCC symposium.

Chemoprevention of keratinocyte carcinoma and actinic keratosis in solid-organ transplant recipients: Systematic review and meta-analyses

To the Editor: Skin cancers account for 40% of malignancies in solid-organ transplant recipients (SOTRs), who have an 80-fold increased risk of squamous cell carcinoma (SCC) and a 16-fold increased risk of basal cell carcinoma (BCC). Systemic chemoprevention is one method to mitigate this amplified risk. Acitretin, for instance, has been used to prevent keratinocyte carcinomas (KC) and actinic keratoses (AK) in SOTRs since 1995,1Bavinck J.N. Tieben L.M. Van der Woude F.J. et al.Prevention of skin cancer and reduction of keratotic skin lesions during acitretin therapy in renal transplant recipients: a double-blind, placebo-controlled study.J Clin Oncol. 1995; 13: 1933-1938Crossref PubMed Google Scholar but its adverse effects include mucositis, liver and lipid abnormalities, and teratogenicity.2George R. Weightman W. Russ G.R. et al.Acitretin for chemoprevention of non-melanoma skin cancers in renal transplant recipients.Australas J Dermatol. 2002; 43: 269-273Crossref PubMed Scopus (130) Google Scholar Nicotinamide, an amide form of vitamin B3, is a newer chemoprophylaxis with fewer adverse effects.3Chen A.C. Martin A.J. Dalziell R.A. et al.A phase II randomized controlled trial of nicotinamide for skin cancer chemoprevention in renal transplant recipients.Br J Dermatol. 2016; 175: 1073-1075Crossref PubMed Scopus (61) Google Scholar Here we report results of a pairwise and network meta-analyses to summarize the current evidence regarding chemoprevention. We selected studies that analyzed the efficacy of systemic chemoprevention to prevent KC/AK in patients who are SOTRs or have a history of 2 or more KCs, or both. We limited our search to placebo-controlled, randomized control trials (RCTs) that reported the number of new KC/AK in both arms. Two authors (L.Y.T., S.Y.C.T.) independently conducted the literature search, screened titles and abstracts for eligibility, and extracted data. Statistical synthesis was performed with RevMan 5.3 software (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark). After the literature search, 6 RCTs with 734 patients were included in the quantitative synthesis (Appendix A, available via Mendeley at https://doi.org/10.17632/m6z2fzkkxn.2). Of the 6 RCTs, 3 studies with 580 patients (range, 17-192 patients) compared nicotinamide to placebo, and 3 studies with 154 patients (range, 19-35 patients) compared acitretin to placebo. Pairwise meta-analysis of all 6 RCTs using a random-effects model demonstrated a significant risk reduction with chemoprevention (Fig 1). The overall mean difference was 0.855 (95% confidence interval, 0.365-1.345; P < .001). In addition, acitretin and nicotinamide were both efficacious, with a combined mean difference of 0.792 (95% confidence interval, 0.298-1.286; P = .00168) for acitretin and a combined mean difference of 4.239 (95% confidence interval, 0.611-7.866; P = .0220) for nicotinamide. A network meta-analysis comparing nicotinamide and acitretin found no significant difference between the 2 treatments (Fig 2, Appendix B).Fig 1Forest plot of the pairwise meta-analysis of randomized controlled trials. The squares indicate the mean difference and are proportional to the weights used in the meta-analysis. The horizontal lines represent the 95% confidence interval (CI). The diamond indicates the weighted mean difference, and the lateral tips of the diamond indicate the associated 95% CI.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Fig 2Network graph and league table of the network meta-analysis. Mean differences and 95% confidence intervals are calculated using a random-effects model. A mean difference >1 means the top-left treatment is better.View Large Image Figure ViewerDownload Hi-res image Download (PPT) This meta-analysis does not address the optimal dosages of the drugs or the frequency of adverse effects. In addition, owing to the limited numbers of eligible RCTs, we are unable to investigate how chemoprevention is influenced by the duration or type of transplantation, duration of systemic chemoprevention, or existing immunosuppressive regimens. Moving forward, topical chemoprevention may be a suitable alternative to systemic chemoprophylaxis in SOTRs. Notably, large RCTs have evaluated topical chemoprevention for actinic keratosis. For instance, the Veterans Affairs Keratinocyte Carcinoma Chemoprevention trial found that topical 5% 5-fluorouracil cream resulted in a 49% relative risk reduction in the number of AK after 6 months and reduced the risk of SCC requiring surgery by 75% after 1 year but did not lower the risk of BCC.4Hyemin P. Hogan D. Eilers D. et al.Long-term efficacy of topical fluorouracil cream 5% for treating actinic keratosis: a randomized clinical trial.JAMA Dermatol. 2015; 151: 952-960Crossref PubMed Scopus (69) Google Scholar,5Weinstock M.A. Thwin S.S. Siegel J.A. et al.Chemoprevention of basal and squamous cell carcinoma with a single course of fluorouracil, 5%, cream: a randomized clinical trial.JAMA Dermatol. 2018; 154: 167-174Crossref PubMed Scopus (54) Google Scholar To our knowledge, this is the first meta-analysis that statistically integrates the current evidence regarding chemoprevention of KC/AK. This study demonstrates that systemic chemoprevention with nicotinamide or acitretin is effective in lowering the risk of KC/AK. Yet, even with the advent of better chemoprevention, regular physician surveillance and sun protection are still key basic strategies that should be practiced by all SOTRs.

Nonmelanoma Skin Cancers in Solid-Organ Transplant Recipients: A Single Center Experience.

Skin cancers are one of the most common malignancies in solid-organ transplant recipients. Increased age and immunosuppressive drug use are risk factors for posttransplant skin malignancies. We evaluated nonmelanocytic skin cancer incidence and development time in transplant patients. We reviewed 1833 patients who received kidney, liver, and heart grafts between 1996 and 2016 at Baskent University. We excluded melanocytic skin cancers, premalignant lesions, and benign skin tumors. Of 1833 patients, 1253 were male (68.4%) and 580 were female (31.6%), composed of 1133 kidney (61.8%), 512 liver (27.9%), and 120 heart recipients (6.5%). Of these, 22 patients (18 kidney/3 liver/1 heart) developed 23 different types of skin cancer. Prevalence of skin cancer was 1.20%. Mean age at presentation was 55.8 years (range, 37-71 y). Average time from transplant to skin malignancy was 6.1 years (range, 1-13 y), with the most common being basal cell carcinoma (43%, 10 cases), followed by squamous cell carcinoma (39%, 9 cases) and Kaposi sarcoma (13%, 3 cases). Tumor sites included head and neck (15 case), trunk (2 cases), lower extremity (2 cases), and upper extremity (2 cases). Neither local recurrence nor distant metastasis was shown. Skin cancer risk is increased in solid-organ transplant recipients versus the general population. Although squamous cell carcinoma is the most common tumor in this patient population, followed by basal cell carcinoma, we found this reversed in our patients. The low prevalence of skin malignancy (1.20%) may be associated with close clinical follow-up to detect premalignant skin lesions and the lowdose immunosuppressive drug regimen. We believe that local recurrence and distant metastasis were absent because we use a wide surgical margin of excision and provide strict follow-up. Routine dermatologic follow-up visits of transplant recipients are recommended to detect and treat early skin cancer and premalignant lesions and thus lower morbidity and mortality.

PIKTYBINIAI ODOS NAVIKAI RECIPIENTAMS PO ORGANŲ TRANSPLANTACIJOS

Ilgalaikis gydymas imunosupresiniais vaistais yra susijęs su piktybinių navikų išsivystymu, iš kurių dažniausi yra odos navikai. Odos karcinomų dažnis recipientams po organų transplantacijos yra didesnis nei bendrojoje populiacijoje. Nemelanocitiniai odos navikai (plokščiųjų ląstelių karcinoma ir bazinių (pamatinių) ląstelių karcinoma) sudaro daugiau nei 90 proc. odos karcinomų, diagnozuojamų šiems pacientams. Ilgą laiką gydomiems imunosupresiniais vaistais taip pat dažniau vystosi ir kiti piktybiniai odos navikai: melanoma, Kapoši sarkoma, Merkelio ląstelių karcinoma, rečiau – odos T ir B ląstelių limfomos. Pastaruoju metu ilgėjant organų recipientų išgyvenamumui, didėja jų sergamumas ir mirštamumas nuo odos karcinomų. Nepaisant to, vis dar trūksta informacijos apie tinkamą šių pacientų stebėjimą ir gydymą. Šiame straipsnyje apžvelgiama piktybinių odos navikų organų recipientams epidemiologija, rizikos veiksniai, profilaktikos ir gydymo principai.

Chemotherapy for malignancies in the post solid organ transplant (SOT) setting: A single institute experience.

TPS6646 Background: Management of advanced malignancies in SOT recipients is not well defined. These patients need immunosuppressive agents to avoid graft rejection. Simultaneous administration of chemotherapy and immunosuppressive agents may increase treatment toxicities. We reviewed data of SOT recipients treated at Roswell Park Cancer Institute (RPCI) for different malignancies to assess their tolerance to treatment and outcomes. Methods: Between 2000-2012, 126 SOT recipients were seen at RPCI for management of cancer. Patients with superficial skin cancer and PTLD or other malignancies not qualifying for therapy were excluded. Adverse events were documented per CTCAE 4.0. Results: 40 patients were included for the review. Median age was 61.5 (29-79) years, and 50% were male. Types of SOT were: 17 liver, 16 kidney, 4 heart, 2 lung and 1 liver/kidney. Types of cancers were: 12 GI, 9 breast, 6 lung, 4 AML/myeloma, 3 head &amp; neck, 2 GYN, 2 skin requiring therapy and 2 GU. Median lag time between SOT and cancer diagnosis was 14.5 years (2m-39y). 13/36 (36%) of solid tumors were metastatic at diagnosis. At the time of analysis, 9/34 (26%) of patients with documented outcome were alive. Of all patients, median overall survival was 28.5m. 31/40 (78%) received chemotherapy and 9/40 (22%) had hormonal therapy alone. In the chemotherapy group, patients received a median of 1.8 lines of therapy (1-6), 4/31 (13%) were given definitive chemotherapy+RT and 8/31 (26%) received chemotherapy in the neoadjuvant/adjuvant setting. Treatment delays were necessary in 10/31 (32%), and dose omission or reduction in 13/31 (42%). The most common hematologic adverse events (AEs) were anemia (25/31, 80%) and thrombocytopenia (19/31, 61%). Febrile neutropenia (G3) occurred in 5/31(16%). The most common non-hematologic AEs were fatigue (23/31, 74%) and hepatic dysfunction (19/31, 61%). The most common G3/4 hematologic AEs were neutropenia (9/31, 29%) and leukopenia (7/31, 23%) while non-hematologic G3/4 AEs were diarrhea and fatigue (4/31 each, 13%). Conclusions: SOT patients tolerate chemotherapy relatively well but AEs, dose reductions and delays occur. Treating physicians should be careful when dosing chemotherapy in these cases.