Certain population groups are known to have higher than average anal cancer risk, namely persons living with HIV (PLHIV), men who have sex with men (MSM), women diagnosed with human papillomavirus (HPV)-related gynecological precancerous lesions or cancer, solid organ transplant recipients (SOTRs) and patients with autoimmune diseases. Our aim was to provide robust and comparable estimates of anal cancer burden across these groups. Summary incidence rates (IRs), as cases per 100 000 person-years (py), were calculated by fixed-effects meta-analysis. IRs were 85 (95% confidence interval [CI] = 82-89) for HIV-positive MSM (n = 7 studies; 2 229 234 py), 32 (95% CI = 30-35) for non-MSM male PLHIV (n = 5; 1626 448 py) and 22 (95% CI = 19-24) for female PLHIV (n = 6; 1 472 123 py), with strong variation by age (eg, from 16.8 < 30 years to 107.5 ≥ 60 years for HIV-positive MSM). IR was 19 (95% CI = 10-36) in HIV-negative MSM (n = 2; 48 135 py). Anal cancer IRs were much higher after diagnosis of vulvar (IR = 48 [95% CI = 38-61]; n = 4; 145 147 py) than cervical (9 [95% CI = 8-12]; n = 4; 779 098 py) or vaginal (IR = 10 [95% CI = 3-30]; n = 4; 32 671) cancer, with equivalent disparity after respective precancerous lesions. IR was 13 (95% CI = 12-15) in SOTRs (n = 5; 1 946 206 py), reaching 24.5 and 49.6 for males and females >10 years after transplant. Anal cancer IRs were 10 (95% CI = 5-19), 6 (95% CI = 3-11) and 3 (95% CI = 2-4) for systemic lupus erythematosus, ulcerative colitis and Crohn's disease, respectively. In conclusion, a unifying anal cancer risk scale, based upon comprehensive meta-analysis, can improve prioritization and standardization in anal cancer prevention/ research initiatives, which are in their public health infancy.

Adoptive cell therapy using autologous tumor-infiltrating lymphocytes (TIL) has shown significant clinical benefit, but is limited by toxicities due to a requirement for post-infusion interleukin-2 (IL-2), for which high dose is standard. To assess a modified TIL protocol using lower dose IL-2, we performed a single institution phase II protocol in unresectable, metastatic melanoma. The primary endpoint was response rate. Secondary endpoints were safety and assessment of immune correlates following TIL infusion. Twelve metastatic melanoma patients were treated with non-myeloablative lymphodepleting chemotherapy, TIL, and low-dose subcutaneous IL-2 (125,000 IU/kg/day, maximum 9-10 doses over 2 weeks). All but one patient had previously progressed after treatment with immune checkpoint inhibitors. No unexpected adverse events were observed, and patients received an average of 6.8 doses of IL-2. By RECIST v1.1, two patients experienced a partial response, one patient had an unconfirmed partial response, and six had stable disease. Biomarker assessment confirmed an increase in IL-15 levels following lymphodepleting chemotherapy as expected and a lack of peripheral regulatory T-cell expansion following protocol treatment. Interrogation of the TIL infusion product and monitoring of the peripheral blood following infusion suggested engraftment of TIL. In one responding patient, a population of T cells expressing a T-cell receptor Vβ chain that was dominant in the infusion product was present at a high percentage in peripheral blood more than 2 years after TIL infusion. This study shows that this protocol of low-dose IL-2 following adoptive cell transfer of TIL is feasible and clinically active. (ClinicalTrials.gov identifier NCT01883323.)

Background Re-excision due to positive margins following breast-conserving surgery (BCS) negatively affects patient outcomes and healthcare costs. The inability to visualize margin involvement is a significant challenge in BCS. 5-Aminolevulinic acid hydrochloride (5-ALA HCl), a non-fluorescent oral prodrug, causes intracellular accumulation of fluorescent porphyrins in cancer cells. This single-center Phase II randomized controlled trial evaluated the safety, feasibility, and diagnostic accuracy of a prototype handheld fluorescence imaging device plus 5-ALA for intraoperative visualization of invasive breast carcinomas during BCS. Methods Fifty-four patients were enrolled and randomized to receive no 5-ALA or oral 5-ALA HCl (15 or 30 mg/kg). Forty-five patients (n = 15/group) were included in the analysis. Fluorescence imaging of the excised surgical specimen was performed, and biopsies were collected from within and outside the clinically demarcated tumor border of the gross specimen for blinded histopathology. Results In the absence of 5-ALA, tissue autofluorescence imaging lacked tumor-specific fluorescent contrast. Both 5-ALA doses caused bright red tumor fluorescence, with improved visualization of tumor contrasted against normal tissue autofluorescence. In the 15 mg/kg 5-ALA group, the positive predictive value (PPV) for detecting breast cancer inside and outside the grossly demarcated tumor border was 100.0% and 55.6%, respectively. In the 30 mg/kg 5-ALA group, the PPV was 100.0% and 50.0% inside and outside the demarcated tumor border, respectively. No adverse events were observed, and clinical feasibility of this imaging device-5-ALA combination approach was confirmed. Conclusions This is the first known clinical report of visualization of 5-ALA-induced fluorescence in invasive breast carcinoma using a real-time handheld intraoperative fluorescence imaging device. Trial registration Clinicaltrials.gov identifier NCT01837225. Registered 23 April 2013.

PurposePatterns of failure and long term outcomes were prospectively evaluated following tumor factors-stratified radiation dose for anal/perianal cancer.MethodsBetween 2008–2013, patients with anal/perianal squamous cell carcinoma were accrued to an institutional REB-approved prospective study. All patients were treated with image-guided intensity-modulated radiation therapy (IG-IMRT). Radiation dose selection (27–36 Gy for elective target, and 45–63 Gy for gross target) was based on tumor clinico-pathologic features. Chemotherapy regimen was 5-fluorouracil/mitomycin-C (weeks 1&5). Local [LF], regional failure [RF], distant metastasis [DM], overall- [OS], disease-free [DFS], colostomy-free survival [CFS] and late toxicity were analyzed.ResultsOverall, 101 patients were evaluated; median follow-up: 56.5 months; 49.5% male; 34.7% T3/4-category, and 35.6% N+. Median radiation dose was 63 Gy. The most common acute grade ≥3 toxicities were skin (41.6%) and hematological (30.7%). Five-year OS, DFS, CFS, LF, RF, DM rates were 83.4%, 75.7%, 74.7, 13.9%, 4.6% and 5% respectively. Five-year LF for patients with T1-2 and T3-4 disease were 0% and 39.2% respectively. All LF (n = 14, after 63 Gy, in tumors ≥5 cm) were in the high dose volume except one marginal to the high dose volume. All RF (n = 4) were within elective dose volume except one within the high dose volume. On multivariable analysis, T3/4-category predicted for poor DFS, CFS and OS. The overall late grade ≥3 toxicity was 36.2% (mainly anal [20%]).ConclusionsIndividualized radiation dose selection using IG-IMRT resulted in good long term outcomes. However, central failures remain a problem for locally advanced tumors even with high dose radiation (63 Gy/7weeks).

Aneurysmal fibrous histiocytoma is an uncommon variant of cutaneous fibrous histiocytomas with a local recurrence rate of 19%. We present a case of aneurysmal fibrous histiocytoma in a 20‐year‐old female with a regional lymph node metastasis and subsequent satellite nodule. The patient initially presented with a 1‐month history of two palpable nodules in left lower anterior shoulder and left axilla. Needle core biopsies from both lesions revealed an atypical spindle cell neoplasm with a differential diagnosis of aneurysmal fibrous histiocytoma and angiomatoid fibrous histiocytoma. The axillary dissection confirmed a metastatic deposit in 1 out of 22 lymph nodes. At 6 months a satellite nodule arose between the resection scar and the axilla histopathologically demonstrating a cellular spindle cell nodule at the dermis subcutaneous junction with large, blood‐filled pseudovascular spaces lined by histiocytes. The periphery of the lesion showed collagen trapping without a lymphoplasmacytic infiltrate. The lesional cells were diffusely positive for CD10 and focally for CD68 and Illumina RNA fusion panel sequencing was negative. Herein we present this case of metastatic aneurysmal fibrous histiocytoma with review of the literature and discussion of biology, cytogenetic alterations, and differential diagnosis.

HLA-restricted T cell responses can induce antitumor effects in cancer patients. Previous human T cell research has largely focused on the few HLA alleles prevalent in a subset of ethnic groups. Here, using a panel of newly developed peptide-exchangeable peptide/HLA multimers and artificial antigen-presenting cells for 25 different class I alleles and greater than 800 peptides, we systematically and comprehensively mapped shared antigenic epitopes recognized by tumor-infiltrating T lymphocytes (TILs) from eight melanoma patients for all their class I alleles. We were able to determine the specificity, on average, of 12.2% of the TILs recognizing a mean of 3.1 shared antigen-derived epitopes across HLA-A, B, and C. Furthermore, we isolated a number of cognate T cell receptor genes with tumor reactivity. Our novel strategy allows for a more complete examination of the immune response and development of novel cancer immunotherapy not limited by HLA allele prevalence or tumor mutation burden.

Young age, teaching hospital, and multiple cancers but not family history were important factors for performing a TAC-IR.

Background Calcification occurs in 12–27% of hepatic colorectal metastases, but its clinical significance and its influence on prognosis are unknown. Methods All patients diagnosed with colorectal liver metastases at the Ottawa Regional Cancer Centre in 1991 (n = 97), as well as those enrolled in chemotherapy trials in 1990–1992 (n = 51), were entered into a retrospective cohort study. Thirty‐six patients were excluded due to inadequate follow‐up. In the remaining 112, abdominal CT scans and/or ultrasound examinations were used to determine the presence of calcification. Charts were reviewed for variables, including primary tumour pathology, amount of liver involvement by tumour (<25%, 25–50%, >50%), and the chemotherapeutic agents received, and were subjected to multivariate and regression analysis. End point was survival in months or to December 1993 (median follow up 24 months). Results Patients with calcification (n = 31) (28%) were compared to those who did not have calcifications (n = 81). The groups were comparable with respect to sex, age, time to calcification, time to metastases, and treatment type. Calcification occurred independent of the degree of tumour differentiation, the presence of mucinous adenocarcinoma, or the hepatic tumour burden. Nine patients with calcified metastases (30%) had calcification at presentation. Biopsies showed calcification next to viable tumour cells with an absence of an inflammatory reaction. Survival was improved with better primary tumour differentiation and less tumour burden. The presence of calcification had a statistically highly significant improvement in survival (P < 10−6, relative risk = .19) independent of other variables. Conclusions The presence of calcification within a colorectal liver metastasis appears to imply a significantly better prognosis. © 1996 Wiley‐Liss, Inc.