Upfront Chemotherapy Followed by Stereotactic Body Radiation Therapy with or without Surgery in Older Patients with Localized Pancreatic Cancer: A Single Institution Experience and Review of the Literature

Objective: To report on clinical outcomes and toxicity in older (age ≥ 70 years) patients with localized pancreatic cancer treated with upfront chemotherapy followed by stereotactic body radiation therapy (SBRT) with or without surgery. Methods: Endpoints included overall survival (OS), local progression-free survival (LPFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and toxicity. Results: A total of 57 older patients were included in the study. Median OS was 19.6 months, with six-month, one-year, and two-year OS rates of 83.4, 66.5, and 42.4%. On MVA, resection status (HR: 0.30, 95% CI 0.12–0.91, p = 0.031) was associated with OS. Patients with surgically resected tumors had improved median OS (29.1 vs. 7.0 months, p < 0.001). On MVA, resection status (HR: 0.40, 95% CI 0.17–0.93, p = 0.034) was also associated with PFS. Patients with surgically resected tumors had improved median PFS (12.9 vs. 1.6 months, p < 0.001). There were 3/57 cases (5.3%) of late grade 3 radiation toxicity and 2/38 cases (5.3%) of Clavien-Dindo grade 3b toxicity in those who underwent resection. Conclusion: Multimodality therapy involving SBRT is safe and feasible in older patients with localized pancreatic cancer. Surgical resection was associated with improved clinical outcomes. As such, older patients who complete chemotherapy should not be excluded from aggressive local therapy when possible.

Endoscopic submucosal dissection for colorectal neoplasia: outcomes and predictors of recurrence

Background and study aims The role of endoscopic submucosal dissection (ESD) for colorectal lesions in Western communities is unclear and its adoption is still limited. The aim of this study is to assess the long-term outcomes of a large cohort of patients treated with colorectal ESD in a tertiary Western center. Patients and methods A retrospective analysis was conducted on patients treated by ESD for superficial colorectal lesions between February 2011 and November 2019. The primary outcome was the recurrence rate. Secondary outcomes were en-bloc and R0 resection rates, procedural time, adverse events (AEs), and need for surgery. The curative resection rate was assessed for submucosal invasive lesions. Results A total of 327 consecutive patients, median age 69 years (IQR 60–76); 201 men (61.5 %) were included in the analysis. Of the lesions, 90.8 % were resected in an en-bloc fashion. The rate of R0 resection was 83.1 % (217/261) and 44.0 % (29/66) for standard and hybrid ESD techniques, respectively. Submucosal invasion and piecemeal resection independently predicted R1 resections. A total of 18(5.5 %) intra-procedural AEs (perforation:11, bleeding:7) and 12(3.7 %) post-procedural AEs occurred (perforation:2, bleeding: 10). Eighteen adenoma recurrences per 1,000 person-years (15cases, 5.6 %) were detected after a median follow-up time of 36 months. All recurrences were detected within 12 months. No carcinoma recurrences were observed. R1 resection status and intra-procedural AEs independently predicted recurrences with seven vs 150 recurrences per 1,000 person-years in the R0 vs R1 group, respectively. Conclusions Colorectal ESD is a safe and effective option for managing superficial colorectal neoplasia in a Western setting, with short and long-terms outcomes comparable to Eastern studies. En-bloc R0 resection and absence of intra-procedural AEs are associated with reduced risk of recurrence.

Children with Supratentorial Midline Pilocytic Astrocytomas Exhibit Multiple Progressions and Acquisition of Neurologic Deficits Over Time

Summary Tumor location has been proposed as a prognostic factor for pilocytic astrocytoma (PA), but since resection status varies by CNS location, these two variables are difficult to separate on multivariate analysis. To eliminate resection status as a confounding variable, we analyzed the outcomes of children with subtotally resected PA by brain location. We found that individuals with PA in the supratentorial midline region had an increased likelihood of multiple progression events. These children also exhibited more neurologic deficits over time compared to those with brainstem PA, frequently due to worsening vision and the acquisition of new endocrinopathies or weakness.

Evaluation of Surgical Therapy in Advanced Thymic Tumors

A complete resection of thymic tumors is known to be the most important prognostic factor, but it is often difficult to perform, especially in advanced stages. In this study, 73 patients with advanced thymic tumors of UICC stages III and IV who underwent radical resection were examined retrospectively. The primary endpoint was defined as the postoperative resection status. Secondary endpoints included postoperative morbidity, mortality, recurrence/progression-free, and overall survival. In total, 31.5% of patients were assigned to stage IIIa, 9.6% to stage IIIb, 47.9% to stage IVa, and 11% to stage IVb. In stages III a R0 resection was achieved in 53.3% of patients. In stages IV a R0/R1 resection was documented in 76.7% of patients. Surgical revision was necessary in 17.8% of patients. In-hospital mortality was 2.7%. Median recurrence/progression-free interval was 43 months (p = 0.19) with an overall survival of 79 months. The 5-year survival rate was 61.3%, respectively. Median survival after R2 resection was 25 months, significantly shorter than after R0 or R1 resection (115 months; p = 0.004). Advanced thymic tumors can be resected with an acceptable risk of complications and low mortality. In stage III as well as in stage IV the promising survival rates are dependent on the resection-status.

Implementation of Multigene Germline and Parallel Somatic Genetic Testing in Epithelial Ovarian Cancer: SIGNPOST Study

We present findings of a cancer multidisciplinary-team (MDT) coordinated mainstreaming pathway of unselected 5-panel germline BRCA1/BRCA2/RAD51C/RAD51D/BRIP1 and parallel somatic BRCA1/BRCA2 testing in all women with epithelial-OC and highlight the discordance between germline and somatic testing strategies across two cancer centres. Patients were counselled and consented by a cancer MDT member. The uptake of parallel multi-gene germline and somatic testing was 97.7%. Counselling by clinical-nurse-specialist more frequently needed >1 consultation (53.6% (30/56)) compared to a medical (15.0% (21/137)) or surgical oncologist (15.3% (17/110)) (p < 0.001). The median age was 54 (IQR = 51–62) years in germline pathogenic-variant (PV) versus 61 (IQR = 51–71) in BRCA wild-type (p = 0.001). There was no significant difference in distribution of PVs by ethnicity, stage, surgery timing or resection status. A total of 15.5% germline and 7.8% somatic BRCA1/BRCA2 PVs were identified. A total of 2.3% patients had RAD51C/RAD51D/BRIP1 PVs. A total of 11% germline PVs were large-genomic-rearrangements and missed by somatic testing. A total of 20% germline PVs are missed by somatic first BRCA-testing approach and 55.6% germline PVs missed by family history ascertainment. The somatic testing failure rate is higher (23%) for patients undergoing diagnostic biopsies. Our findings favour a prospective parallel somatic and germline panel testing approach as a clinically efficient strategy to maximise variant identification. UK Genomics test-directory criteria should be expanded to include a panel of OC genes.

Efficacy of Location-Based Features for Survival Prediction of Patients With Glioblastoma Depending on Resection Status

Cancer stands out as one of the fatal diseases people are facing all the time. Each year, a countless number of people die because of the late diagnosis of cancer or wrong treatments. Glioma, one of the most common primary brain tumors, has different aggressiveness and sub-regions, which can affect the risk of disease. Although prediction of overall survival based on multimodal magnetic resonance imaging (MRI) is challenging, in this study, we assess if and how location-based features of tumors can affect overall survival prediction. This approach is evaluated independently and in combination with radiomic features. The process is carried out on a data set entailing MRI images of patients with glioblastoma. To assess the impact of resection status, the data set is divided into two groups, patients were reported as gross total resection and unknown resection status. Then, different machine learning algorithms were used to evaluate how location features are linked with overall survival. Results from regression models indicate that location-based features have considerable effects on the patients’ overall survival independently. Additionally, classifier models show an improvement in prediction accuracy by the addition of location-based features to radiomic features.

Outcomes following Upfront Radiation versus Monitoring in Atypical Meningiomas: 16-year Experience at a Tertiary Medical Center

Background The role of post-operative upfront radiotherapy (RT) in the management of gross totally resected atypical meningiomas remains unclear. This single-center retrospective review of newly-diagnosed histologically-confirmed cases of World Health Organization (WHO) Grade II atypical meningioma at Weill Cornell Medicine from 2004-2020 aims to compare overall survival (OS) and progression free survival (PFS) of post-operative upfront radiotherapy versus observation, stratified by resection status (gross total resection [GTR)] versus subtotal resection [STR]). Methods 90 cases of atypical meningioma were reviewed (56% women; median age 61 years; median follow-up 41 months). Results In patients with GTR, hazard ratio (HR) of PFS was 0.09 for post-operative upfront RT versus observation alone (95% confidence interval [CI] 0.01-0.68; p = 0.02), though HR for OS was not significant (HR 0.46; 95% CI 0.05-4.45; p = 0.5). With RT, PFS was 100% at 12 and 36 months (compared to 84% and 63% respectively with observation); OS at 36 months was 100% (compared to 94% with observation). In patients with STR, though PFS at 36 months was higher for RT arm versus observation (84% versus 74%), OS at 36 months was 100% in both arms. HR was not significant (HR 0.76; 95% CI 0.16-3.5; p = 0.73). Conclusion This retrospective study suggests post-operative upfront radiotherapy following GTR of atypical meningioma is associated with improved PFS compared to observation. Further studies are required to draw conclusions about OS.

Avidity and outcomes of radioiodine therapy for distant metastasis of distinct types of differentiated thyroid cancer

Context The recommendations for radioiodine therapy (RAIT) in metastatic differentiated thyroid cancer (DTC) are mostly based in the experience with papillary histotype and do not consider the differences within the distinct types of DTC, in terms of RAIT uptake and response. Objective To investigate the association between histology and RAIT avidity and response; to evaluate whether histotype was an independent prognostic factor in progression-free survival (PFS) and disease-specific survival (DSS) after RAIT for distant metastatic disease. Design Retrospective analysis of all DTC patients submitted to RAIT due to distant metastatic disease, between 2001-2018. Setting Thyroid cancer referral centre. Patients We included 126 patients: 42 (33.3%) classical variant papillary thyroid cancer (cvPTC), 45 (35.7%) follicular variant PTC (fvPTC), 17 (13.5%) follicular thyroid cancer (FTC) and 22 (17.5%) Hürthle-cell carcinoma. Main outcome measures RAIT avidity and response. Results RAIT avidity was independently associated with histology (p&lt;0.001) and stimulated thyroglobulin at first RAIT for distant lesions (p=0.007). Avidity was lowest in HCC (13.6%), intermediate in cvPTC (21.4%), and highest in fvPTC (75.6%) and FTC (76.5%). Regarding RAIT response, HCC and FTC were not different; both showed significantly more often progression after RAIT than fvPTC and cvPTC. Histology influenced PFS (p=0.014), but tumour type was not a significant prognostic factor in DSS. Instead, age at diagnosis, resection status, and stimulated thyroglobulin at the first RAIT were significantly associated with DSS. Conclusion DTC histotype influenced RAIT avidity and PFS. It is crucial to better detect the metastatic patients that may benefit the most from RAIT.

Modified GRAS Score for Prognostic Classification of Adrenocortical Carcinoma: An ENSAT Multicentre Study

Background: Adrenocortical carcinoma (ACC) has an aggressive but heterogeneous behaviour. ENSAT stage and Ki67 proliferation index are used to predict clinical outcome but are limited in distinguishing patients with different risk of disease progress. We aimed to validate the prognostic role of a previously proposed points-based score (mGRAS) in a large ACC cohort. Methods: We included ACC patients who underwent adrenalectomy between 2010 and 2019, had complete clinical and histopathological data, and did not participate in our previous studies (Libe et al. Ann Oncol 2015; Lippert et al. JCEM 2018). The mGRAS score was calculated as follows: age (&lt;50yr=0; ≥50yr =1), symptoms (no=0; yes=1), ENSAT stage (1–2=0; 3=1; 4=2), resection status (R0=0; RX=1; R1=2; R2=3), and Ki67 (0–9%=0; 10–19%=1; ≥20%=2 points), generating scores from 0 to 9 and four mGRAS groups (scores 0–1, 2–3, 4–5, and 6–9). Progression-free survival (PFS) and disease-specific survival (DSS) were the primary and secondary endpoints, respectively. The discriminative performance of mGRAS was investigated using the Harrell’s C-index and Royston-Sauerbrei’s R2D statistic. Results: A total of 942 ACC patients from 14 ENSAT centres were included (38% men; median age 50yrs (interquartile range 38, 61)). The four mGRAS groups showed superior prognostic discrimination compared to the individual clinical and histological parameters for both PFS and DSS (C-index 0.71, R2D=0.30 and 0.77, R2D=0.46, respectively); ENSAT staging was the second best discriminator (C-index 0.67, R2D 0.21 and 0.72, R2D=0.35, respectively). An even better prognostic discrimination was observed using the ten mGRAS scores individually (C-index 0.73, R2D=0.30, and 0.79, R2D=0.45 for PFS and DSS, respectively). The superiority of mGRAS was confirmed when separately considering patients treated or untreated with adjuvant mitotane (n=481 vs 314). In mitotane-treated patients, the four mGRAS groups showed better performance in predicting PFS than Ki67 index (C-index 0.66, R2D 0.18 vs C-index 0.62, R2D 0.12). Conclusion: The prognostic performance of mGRAS is superior to that of ENSAT staging and Ki67. This simple score may guide personalised treatment decisions in patients with ACC, e.g. regarding the need for adjuvant therapy and frequency of monitoring.