Gastric-type adenocarcinoma of the cervix in patients with Peutz-Jeghers syndrome: a systematic review of the literature with proposed screening guidelines.

OBJECTIVES: To perform a systematic review of gastric-type adenocarcinoma of the cervix and lobular endocervical glandular hyperplasia (a possible precursor lesion) in Peutz-Jeghers syndrome, and to analyze data from the literature, along with our institutional experience, to determine recommendations for screening and detection. METHODS: A comprehensive literature searc and retrospective search of pathology records at our institutio were conducted. Articles were screened by two independent reviewers. Case reports/series on lobular endocervical glandular hyperplasia/gastric-type adenocarcinoma of the cervix in Peutz-Jeghers syndrome were included. Demographic, clinical, and radiologic information was collected. RESULTS: A total of 1564 publications were reviewed; 38 met the inclusion criteria. Forty-nine were included in the analysis (43 from the literature, 6 from our institution). Forty-three reported on gastric-type adenocarcinoma alone, 4 on lobular endocervical glandular hyperplasia alone, and 2 on concurrent lobular endocervical glandular hyperplasia/gastric-type adenocarcinoma. Median age at diagnosis was 17 (range, 4-52) for patients with lobular endocervical glandular hyperplasia alone and 35 (range, 15-72) for those with gastric-type adenocarcinoma. The most common presenting symptoms were abdominal/pelvic pain and vaginal bleeding/discharge. Imaging was reported for 27 patients; 24 (89%) had abnormal cervical features. Papanicolaou (Pap) smear prior to diagnosis was reported for 12 patients; 6 (50%) had normal cytology, 4 (33%) atypical glandular cells, and 2 (17%) atypical cells not otherwise specified. Patients with gastric-type adenocarcinoma (n=45) were treated with surgery alone (n=16), surgery/chemotherapy/radiation (n=11), surgery/chemotherapy (n=9), surgery/radiation (n=5), or radiation/chemotherapy (n=4). Twelve (27%) of 45 patients recurred; median progression-free survival was 10 months (range, 1-148). Twenty patients (44%) died; median overall survival was 26 months (range, 2-156). Thirteen patients (27%) were alive with no evidence of disease. CONCLUSIONS: Gastric-type adenocarcinoma in Peutz-Jeghers syndrome is associated with poor outcomes and short progression-free and overall survival. Screening recommendations, including pathognomonic symptom review and physical examination, with a low threshold for imaging and biopsy, may detect precursor lesions and early-stage gastric-type adenocarcinoma, leading to better outcomes in this high-risk population. PROSPERO REGISTRATION NUMBER: CRD42019118151.

Pattern of disease and response to pembrolizumab in recurrent cervical cancer.

OBJECTIVE: Since the approval of pembrolizumab for advanced or recurrent PD-L1 positive (CPS > 1%) cervical cancer, the clinical characteristics associated with response have remained undefined. We sought to characterize the clinicopathologic features of patients with advanced cervical cancer at our institution who derived durable clinical benefit from treatment with pembrolizumab. METHODS: We conducted a retrospective cohort study of 14 patients with recurrent or metastatic cervical cancer who received pembrolizumab monotherapy from August 2017 to November 2019 and were followed until November 1, 2020. Reviewed clinical data included age, histology, tumor molecular profiling results, stage at diagnosis, treatment history, baseline pattern of metastatic disease at initiation of anti-PD-1 therapy, and outcomes. Treatment response was evaluated by computed tomography using RECIST v1.1 criteria. RESULTS: The objective response rate was 21% (n = 3), including two partial responses and one complete response. Two patients (14%) had stable disease of six months or greater, for an observed durable clinical benefit rate of 36%. When stratified by those who derived clinical benefit, metastatic spread to lung and/or lymph node only at baseline was associated with improved response to pembrolizumab (n = 7, p = 0.02) and associated with significantly improved PFS and OS. Tumor mutational burden was higher in those with durable clinical benefit compared to non-responders (median 12.7 vs. 3.5 mutations/megabase, p = 0.03). CONCLUSIONS: Our findings highlight clinical features that may select for a population most likely to benefit from pembrolizumab monotherapy and underscores the need for identification of additional biomarkers of response.

Prognostic significance of supraclavicular lymphadenopathy in patients with high-grade serous ovarian cancer.

OBJECTIVES: To assess outcomes and patterns of recurrence in patients with high-grade serous ovarian/tubal/primary peritoneal cancers with radiographic supraclavicular lymphadenopathy at diagnosis. METHODS: We evaluated all patients with newly diagnosed high-grade serous ovarian cancers treated at our center between January 1, 2008 and May 1, 2013 who had supraclavicular lymphadenopathy (defined as ≥1 cm in short axis) on radiographic imaging (either computed tomography or positron emission tomography) at the time of diagnosis. RESULTS: Of 586 patients with high-grade serous ovarian cancer receiving primary treatment during the study period, we identified 13 (2.2%) with supraclavicular lymphadenopathy diagnosed on pre-treatment imaging. The median age at diagnosis was 52.0 years (range 38.2-72.3). Five (31%) had clinically palpable nodes on physical examination. Four (31%) had a known BRCA mutation. All 13 patients underwent neoadjuvant chemotherapy, followed by interval debulking surgery. Each patient received a median of four cycles of neoadjuvant intravenous chemotherapy (range 3-7). At interval debulking surgery, complete gross resection was achieved in nine (70%) patients, and optimal resection (0.1-1 cm residual disease) in four (30%). Eleven patients (85%) recurred; however, only one (8%) recurred in the supraclavicular lymph nodes. Median follow-up time was 44.3 months (range 22.4-95.0). Median progression-free survival for the cohort was 11.7 months (95% CI 9.2 to 14.1). Median overall survival was 44.3 months (95% CI 41.5 to 47.1). In patients obtaining complete gross resection at interval debulking surgery, median progression-free survival and overall survival were 13.9 months (95% CI 8.9 to 18.9) and 78.1 months (95% CI 11.1 to 145.1), respectively. CONCLUSIONS: In our study, approximately 2% of patients with high-grade serous ovarian cancer presented with radiographic evidence of supraclavicular lymphadenopathy. Supraclavicular lymphadenopathy at diagnosis did not portend an unfavorable outcome when complete gross resection was achieved at interval debulking surgery.

Prognostic utility of differential tissue characterization of cardiac neoplasm and thrombus via late gadolinium enhancement cardiovascular magnetic resonance among patients with advanced systemic cancer.

BACKGROUND: Late gadolinium enhancement (LGE-) cardiovascular magnetic resonance (CMR) is well-validated for cardiac mass (CMASS) tissue characterization to differentiate neoplasm (CNEO) from thrombus (CTHR): Prognostic implications of CMASS subtypes among systemic cancer patients are unknown. METHODS: CMASS + patients and controls (CMASS -) matched for cancer diagnosis and stage underwent a standardized CMR protocol, including LGE-CMR (IR-GRE) for tissue characterization and balanced steady state free precession cine-CMR (SSFP) for cardiac structure/function. CMASS subtypes (CNEO, CTHR) were respectively defined by presence or absence of enhancement on LGE-CMR; lesions were quantified for tissue properties (contrast-to-noise ratio (CNR); signal-to-noise ratio (SNR) and size. Clinical follow-up was performed to evaluate prognosis in relation to CMASS etiology. RESULTS: The study population comprised 126 patients with systemic neoplasms referred for CMR, of whom 50% (n = 63) had CMASS + (CNEO = 32%, CTHR = 18%). Cancer etiology differed between CNEO (sarcoma = 20%, lung = 18%) and CTHR (lymphoma = 30%, GI = 26%); cardiac function (left ventricular ejection fraction: 63 ± 9 vs. 62 ± 10%; p = 0.51∣ right ventricular ejection fraction: 53 ± 9 vs. 54 ± 8%; p = 0.47) and geometric indices were similar (all p = NS). LGE-CMR tissue properties assessed by CNR (13.1 ± 13.0 vs. 1.6 ± 1.0; p < 0.001) and SNR (29.7 ± 20.4 vs. 15.0 ± 11.4, p = 0.003) were higher for CNEO, consistent with visually-assigned diagnostic categories. CTHR were more likely to localize to the right atrium (78% vs. 25%, p < 0.001); nearly all (17/18) were associated with central catheters. Lesion size (17.3 ± 23.8 vs. 2.0 ± 1.5 cm2; p < 0.001) was greater with CNEO vs. CTHR, as was systemic disease burden (cancer-involved organs: 3.6 ± 2.0 vs. 2.3 ± 2.1; p = 0.02). Mortality during a median follow-up of 2.5 years was markedly higher among patients with CNEO compared to those with CTHR (HR = 3.13 [CI 1.54-6.39], p = 0.002); prognosis was similar when patients were stratified by lesion size assessed via area (HR = 0.99 per cm2 [CI 0.98-1.01], p = 0.40) or maximal diameter (HR = 0.98 per cm [CI 0.91-1.06], p = 0.61). CTHR conferred similar mortality risk compared to cancer-matched controls without cardiac involvement (p = 0.64) whereas mortality associated with CNEO was slightly higher albeit non-significant (p = 0.12). CONCLUSIONS: Among a broad cancer cohort with cardiac masses, CNEO defined by LGE-CMR tissue characterization conferred markedly poorer prognosis than CTHR, whereas anatomic assessment via cine-CMR did not stratify mortality risk. Both CNEO and CTHR are associated with similar prognosis compared to CMASS - controls matched for cancer type and disease extent.