Prognosis and risk of suicide after cancer diagnosis.

INTRODUCTION: Suicide rates are elevated after cancer diagnosis. Existential distress caused by awareness of one's impending death is well-described in patients with cancer. The authors hypothesized that suicide risk is associated with cancer prognosis, and the impact of prognosis on suicide risk is greatest for populations with higher baseline suicide risk. METHODS: The authors identified patients (≥16 years old) with newly diagnosed cancers from 2000 to 2019 in the Surveillance, Epidemiology, and End Results database, representing 27% of US cancers. Multiple primary-standardized mortality ratios (SMR) were used to estimate the relative risk of suicide within 6 months of diagnosis compared to the general US population, adjusted for age, sex, race, and year of follow-up. Suicide rates by 20 most common cancer sites were compared with respective 2-year overall survival rates (i.e., prognosis) using a weighted linear regression model. RESULTS: Among 6,754,704 persons diagnosed with cancer, there were 1610 suicide deaths within 6 months of diagnosis, three times higher than the general population (SMR = 3.1; 95% confidence interval, 3.0-3.3). Suicide risk by cancer site was closely associated with overall prognosis (9.5%/percent survival deficit, R2  = 0.88, p < .0001). The association of prognosis with suicide risk became attenuated over time. For men, the risk of suicide increased by 2.8 suicide deaths per 100,000 person-years (p < .0001) versus 0.3 in women (p < .0001). The risk was also higher for persons ≥60 old and for the White (vs. Black) race. CONCLUSIONS: Poorer prognosis was closely associated with suicide risk early after cancer diagnosis and had a greater effect on populations with higher baseline risks of suicide. This model highlights the need for enhanced psychiatric surveillance and continued research in this patient population.

MGMT promoter methylation in 1p19q-intact gliomas.

OBJECTIVE: Standard-of-care for 1p19q-intact anaplastic gliomas is defined by the international randomized phase III CATNON trial, which found an overall survival (OS) benefit for adjuvant temozolomide (TMZ) when added to radiotherapy. Paradoxically, TMZ did not appear to benefit patients with IDH-wildtype gliomas, regardless of MGMT promoter status. The authors concluded that well-powered prospective study on the clinical efficacy of TMZ for patients with IDH-wildtype anaplastic gliomas (meeting criteria for glioblastoma) is warranted. Given that the prognostic and predictive role of MGMT status for grade 2-3 gliomas is unresolved, we determined the effect of MGMT status on OS in patients with 1p19q-intact gliomas in the National Cancer Database (NCDB). METHODS: We queried the NCDB from 2018 to 2019 for patients with diffuse (grade 2) and anaplastic (grade 3) IDH-wildtype or -mutant astrocytomas who received chemotherapy with follow-up through 2022. The Kaplan-Meier method and Cox proportional hazards regressions models were used to determine the association of MGMT with OS. RESULTS: We identified 1514 patients who were newly diagnosed with IDH-wildtype (n = 802, 33% methylated) or -mutant astrocytomas (n = 712, 48% methylated) and received chemotherapy during initial management. An unmethylated promoter was associated with poorer survival in patients with IDH-wildtype (3-year OS 34% [95%CI 29-39%] vs. 46% [95%CI 39-54%], p < .001, adjusted HR 1.53 [95%CI 1.24-1.89]) but not IDH-mutant astrocytomas (3-year OS 79% [95%CI 74-84%] vs. 80% [95%CI 75-86%], p =0 .81, HR 1.04 [95%CI 0.73-1.50]). CONCLUSIONS: This ancillary analysis supports conclusions from the CATNON trial for adjuvant TMZ as standard-of-care for anaplastic astrocytomas (IDH-mutant and 1p19q-intact), irrespective of MGMT status. Determining the optimal strategy for diffuse gliomas that are IDH-wildtype will be particularly important. MGMT promoter methylation should be considered as a stratification factor in future clinical trials for these patients.

Risk of corticosteroid treatment and hospitalization after checkpoint inhibitor and radiation therapy in patients with cancer.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are potent new cancer therapies but can cause serious immune-related adverse events. ICIs have contributed significantly to improved survival and thereby provide more opportunity for the development of local disease symptomatology requiring palliative radiation. Radiation therapy (RT) has also recently shown benefit in the oligometastatic setting. Data on the interaction and safety of concurrent ICIs and RT are limited. METHODS: In this retrospective cohort study using a large medical claims database from 2010 to 2017, the need for corticosteroid therapy and the risk of hospitalization within 180 days of treatment with an ICI were determined for patients with a diagnosis of malignant melanoma or lung cancer. Patients were stratified by the use of RT within the 30 days before and after ICI therapy. RESULTS: In all, 2020 patients (218 with RT and 1802 without RT) met the inclusion criteria for prednisone analysis, whereas 3519 patients (361 with RT and 3158 without RT) met the inclusion criteria for all other analyses. In a univariable analysis, RT was not associated with the need for prednisone (relative risk [RR], 1.2; 95% confidence interval [CI], 0.8-1.9) or methylprednisolone (RR, 1.1; 95% CI, 0.7-2.0). When the end point was hospitalization, RT was significantly associated with hospitalization after ICI therapy for certain cancer/drug combinations (RR for lung cancer/programmed death 1 receptor inhibitors, 1.4; 95% CI, 1.2-1.6; P < .001; RR for melanoma/ipilimumab, 2.0; 95% CI, 1.0-3.5; P = .03). CONCLUSIONS: In patients treated with ICIs, receiving RT was not associated with a higher risk of requiring corticosteroid therapy in comparison with not receiving RT. However, RT was associated with a higher risk of hospitalization, although this finding may be a result of differences in the underlying patient illness severity or oncologic disease burden at the baseline. LAY SUMMARY: Data on the interaction of immunotherapy (immune checkpoint inhibitors) and radiation therapy and the safety of combining them are limited. Using a large database, this study has found that patients treated concurrently with immune checkpoint inhibitors and radiation therapy are not at increased risk for requiring corticosteroid therapy (which is used as a proxy for immune-related adverse events). However, concurrent therapy is associated with a higher risk of hospitalization, although this finding may be due to differences in the underlying patient illness severity (sicker patients may require both immunotherapy and radiation therapy).

Neoadjuvant atezolizumab and chemotherapy in patients with resectable non-small-cell lung cancer: an open-label, multicentre, single-arm, phase 2 trial.

BACKGROUND: Approximately 25% of all patients with non-small-cell lung cancer present with resectable stage IB-IIIA disease, and although perioperative chemotherapy is the standard of care, this treatment strategy provides only modest survival benefits. On the basis of the activity of immune checkpoint inhibitors in metastatic non-small-cell lung cancer, we designed a trial to test the activity of the PD-L1 inhibitor, atezolizumab, with carboplatin and nab-paclitaxel given as neoadjuvant treatment before surgical resection. METHODS: This open-label, multicentre, single-arm, phase 2 trial was done at three hospitals in the USA. Eligible patients were aged 18 years or older and had resectable American Joint Committee on Cancer-defined stage IB-IIIA non-small-cell lung cancer, an Eastern Cooperative Oncology Group performance status of 0-1, and a history of smoking exposure. Patients received neoadjuvant treatment with intravenous atezolizumab (1200 mg) on day 1, nab-paclitaxel (100 mg/m2) on days 1, 8, and 15, and carboplatin (area under the curve 5; 5 mg/mL per min) on day 1, of each 21-day cycle. Patients without disease progression after two cycles proceeded to receive two further cycles, which were then followed by surgical resection. The primary endpoint was major pathological response, defined as the presence of 10% or less residual viable tumour at the time of surgery. All analyses were intention to treat. This study is registered with ClinicalTrials.gov, NCT02716038, and is ongoing but no longer recruiting participants. FINDINGS: Between May 26, 2016, and March 1, 2019, we assessed 39 patients for eligibility, of whom 30 patients were enrolled. 23 (77%) of these patients had stage IIIA disease. 29 (97%) patients were taken into the operating theatre, and 26 (87%) underwent successful R0 resection. At the data cutoff (Aug 7, 2019), the median follow-up period was 12·9 months (IQR 6·2-22·9). 17 (57%; 95% CI 37-75) of 30 patients had a major pathological response. The most common treatment-related grade 3-4 adverse events were neutropenia (15 [50%] of 30 patients), increased alanine aminotransferase concentrations (two [7%] patients), increased aspartate aminotransferase concentration (two [7%] patients), and thrombocytopenia (two [7%] patients). Serious treatment-related adverse events included one (3%) patient with grade 3 febrile neutropenia, one (3%) patient with grade 4 hyperglycaemia, and one (3%) patient with grade 2 bronchopulmonary haemorrhage. There were no treatment-related deaths. INTERPRETATION: Atezolizumab plus carboplatin and nab-paclitaxel could be a potential neoadjuvant regimen for resectable non-small-cell lung cancer, with a high proportion of patients achieving a major pathological response, and manageable treatment-related toxic effects, which did not compromise surgical resection. FUNDING: Genentech and Celgene.

Surgery plus adjuvant radiotherapy for primary central nervous system lymphoma.

Objective: Recent studies of primary central nervous system lymphoma (PCNSL) have found a positive association between cytoreductive surgery and survival, challenging the traditional notion that surgery is not beneficial and potentially harmful. However, no studies have examined the potential added benefits of adjuvant treatment in the post-operative setting. Here, we investigate survival in PCNSL patients treated with surgery plus radiation therapy (RT).Methods: The Surveillance, Epidemiology, and End-Results Program was used to identify patients with PCNSL from 1995-2013. We retrospectively analyzed the relationship between treatment, prognostic factors, and survival using case-control design. Treatment categories were compared to biopsy alone.Results: We identified 5417 cases. Median survival times for biopsy alone (n = 1824, 34%), biopsy + RT (n = 1460, 27%), surgery alone (n = 1222, 27%), and surgery + RT (n = 911, 17%) were 7, 8, 20, and 27 months, respectively. On multivariable analysis, surgery + RT was associated with improved survival over surgery alone (hazard ratio [HR] = 0.58 [95% confidence interval = 0.53-0.64] vs. HR = 0.71 [0.65-0.77]). Adjuvant RT was associated with improved survival, regardless of the extent of resection. HR's for subtotal resection, gross-total resection, subtotal resection + RT, and gross-total resection + RT were 0.77 (0.66-0.89), 0.66 (0.57-0.76), 0.62 (0.52-0.72), and 0.54 (0.46-0.63), respectively. Survival improved after adjuvant RT in patients under and over 60 years old. All findings were confirmed by multivariable analysis of cause-specific survival.Conclusion: Adjuvant RT was associated with improved survival in PCNSL patients who underwent surgery. Although these data are hypothesis-generating, additional information on neurotoxicity, dosing, and concurrent chemotherapy will be necessary to validate these findings. Cytoreductive surgery for PCNSL is common in the general population, and more studies are needed to assess optimal treatment in the post-operative setting.

Spinal location is prognostic of survival for solitary-fibrous tumor/hemangiopericytoma of the central nervous system.

BACKGROUND: Prior studies have highlighted infratentorial tumor location as a prognostic factor for solitary fibrous tumor (SFT) and hemangiopericytoma (HPC) of the central nervous system (CNS), and spinal location is considered a positive prognostic factor for other tumors of the CNS. While SFT/HPC of the CNS is known to frequently arise from the spinal meninges, there are no case series that report outcomes for spinally located CNS tumors, and their prognosis in relation to intracranial and other CNS-located tumors is unknown. OBJECTIVE: To investigate outcomes for patients with SFT/HPC of the spinal meninges. METHODS: The Surveillance, Epidemiology, and End-Results Program was used to identify patients with SFT/HPC within the CNS from 1993-2015. We retrospectively analyzed the relationship between tumor location (spinal vs. Brain and other CNS) and survival. RESULTS: We identified 551 cases of CNS SFT/HPC, 64 (11.6%) of which were primary tumors of the spinal meninges. Spinal tumors were more likely than brain and other CNS tumors to be SFT vs. HPC (37.5 vs. 12%, p < 0.001), benign (42.2 vs. 20.3%, p < 0.001), and less than 5 cm (53.1 vs. 35.7%, p < 0.001). The 10-year survival rates for spinal and brain/other CNS tumors were 85 and 58%, respectively. Median survival time was significantly longer for spinal tumors (median survival not reached vs. 138 months, p = 0.03, HR = 0.41 [95% CI 0.18-0.94]). On multivariable analysis, spinal tumor location was associated with improved survival over tumors located in the brain and other CNS (HR = 0.36 [95% CI 0.15-0.89], p = 0.03). CONCLUSION: Spinal tumor location is associated with improved survival in patients with SFT/HPC of the CNS. Larger institutional studies are necessary to characterize the relationship between tumor location and other relevant factors such as presentation and amenability to gross-total resection and adjuvant radiotherapy. Future studies exploring optimal management of spinally located tumors are also needed.

Extent of resection and survival for oligodendroglioma: a U.S. population-based study.

BACKGROUND: National guidelines recommend maximal safe resection of low-grade and high-grade oligodendrogliomas. However, there is no level 1 evidence to support these guidelines, and recent retrospective studies on the topic have yielded mixed results. OBJECTIVE: To assess the association between extent of resection (EOR) and survival for oligodendrogliomas in the general U.S. METHODS: Cases diagnosed between 2004 and 2013 were selected from the Surveillance, Epidemiology, and End-Results (SEER) Program and retrospectively analyzed for treatment, prognostic factors, and survival times. Cases that did not undergo tumor de-bulking surgery (e.g. no surgery or biopsy alone) were compared to subtotal resection (resection) and gross-total resection (GTR). The primary end-points were overall survival (OS) and cause-specific survival (CSS). An external validation cohort with 1p/19q-codeleted tumors was creating using the TCGA and GSE16011 datasets. RESULTS: 3135 Cases were included in the final analysis. The 75% survival time (75ST) and 5-year survival rates were 47 months and 70.8%, respectively. Subtotal resection (STR, 75ST = 50 months) and GTR (75ST = 61 months) were associated with improved survival times compared to cases that did not undergo surgical debulking (75ST = 20 months, P < 0.001 for both), with reduced hazard ratios (HRs) after controlling for other factors (HR 0.81 [0.68-0.97] and HR 0.65 [0.54-0.79], respectively). GTR was associated with improved OS in both low-grade and anaplastic oligodendroglioma subgroups (HR 0.74 [0.58-0.95], HR 0.60 [0.44-0.82], respectively) while STR fell short of significance in the subgroup analysis. All findings were corroborated by multivariable analysis of CSS and externally validated in a cohort of patients with 1p19q-codeleted tumors. CONCLUSION: Greater EOR is associated with improved survival in oligodendrogliomas. Our findings in this U.S. population-based cohort support national guidelines.

Natural history, clinical course and predictors of interval time from initial diagnosis to development of subsequent NSCLC brain metastases.

PURPOSE: Non-small cell lung cancer (NSCLC) brain metastases are associated with substantial morbidity and mortality. During recent years, accompanying dramatic improvements in systemic disease control, NSCLC brain metastases have emerged as an increasingly relevant clinical problem. However, optimal surveillance practices remain poorly defined. This purpose of this study was to further characterize the natural history, clinical course and risk factors associated with earlier development of subsequent NSCLC brain metastases to better inform clinical practice and help guide survivorship care. METHODS: We retrospectively reviewed all institutional NSCLC brain metastasis cases treated with radiotherapy between 1997 and 2015. Exclusion criteria included presence of brain metastases at initial NSCLC diagnosis and incomplete staging information. Interval time to brain metastases and subsequent survival were characterized using Kaplan-Meier and multivariate Cox regression analyses. RESULTS: Among 105 patients within this cohort, median interval time to development of brain metastases was 16 months. Median interval times were 29, 19, 16 and 13 months for Stage I-IV patients, respectively (P = 0.016). Additional independent predictors for earlier development of NSCLC brain metastases included non-adenocarcinomatous histopathology (HR 3.036, P < 0.001), no prior surgical resection (HR 1.609, P = 0.036) and no prior systemic therapy (HR 3.560, P = 0.004). Median survival following intracranial progression was 16 months. Delayed development of brain metastases was associated with better prognosis (HR 0.970, P < 0.001) but not survival following intracranial disease onset. CONCLUSIONS: Collectively, our results provide valuable insights into the natural history of NSCLC brain metastases. NSCLC stage, histology, prior surgical resection and prior systemic therapy emerged as independent predictors for interval time to brain metastases.

Clinical and molecular characteristics of gliosarcoma and modern prognostic significance relative to conventional glioblastoma.

Gliosarcoma is a rare histopathologic variant of glioblastoma traditionally associated with a poor prognosis. While gliosarcoma may represent a distinct clinical entity given its unique histologic composition and molecular features, its relative prognostic significance remains uncertain. While treatment of gliosarcoma generally encompasses the same standardized approach used in glioblastoma, supporting evidence is limited given its rarity. Here, we characterized 32 cases of gliosarcoma and retrospectively evaluated survival relative to 451 glioblastoma patients diagnosed during the same era within the same institution. Overall, we identified 22 primary gliosarcomas, representing 4.7% of WHO Grade IV primary glioblastomas, and 10 secondary gliosarcomas. With median age of 62, patients were predominately Caucasian (87.5%) and male (65.6%). Tumors with available molecular profiling were primarily MGMT-unmethylated (87.5%), IDH-1-preserved (100%) and EGFR wild-type (100%). Interestingly, while no significant median survival difference between primary gliosarcoma and glioblastoma was observed across the entire cohort (11.0 vs. 14.8 months, p = 0.269), median survival was worse for gliosarcoma specifically among patients who received modern temozolomide-based (TMZ) chemoradiotherapy (11.0 vs. 17.3 months, p = 0.006). Matched-pair analysis also trended toward worse median survival among gliosarcomas (11.0 vs. 19.6 months, log-rank p = 0.177, Breslow p = 0.010). While adjuvant radiotherapy (HR 0.206, p = 0.035) and TMZ-based chemotherapy (HR 0.531, p = 0.000) appeared protective, gliosarcoma emerged as a significantly poor prognostic factor on multivariate analysis (HR 3.27, p = 0.012). Collectively, our results suggest that gliosarcoma may still portend worse prognosis even with modern trimodality therapy.

Local control and overall survival for adjuvant stereotactic radiosurgery in patients with residual or recurrent disease.

Prior studies of post-operative stereotactic radiosurgery (SRS) have not distinguished between Adjuvant SRS (ARS) versus Adjuvant SRS to residual/recurrent disease (ARD). In this study, we defined ARS and ARD and investigated local control (LC), overall survival (OS), distant development of brain metastases (DBF), and leptomeningeal disease (LMD). We retrospectively identified BM patients who received surgical resection and SRS for BM from an IRB approved database between Jan 2009-Aug 2015. Patients were stratified into two groups: ARS and ARD. LC was determined by follow-up MRI studies and OS was measured from the date of surgery. LC and OS were assessed using the Kaplan-Meier method. 70 cavities underwent surgical resection of BM and received SRS to the post-operative bed. 41 cavities were classified as ARS and 29 as ARD. There was no significant difference in 12-month LC between the ARS and ARD group (71.4 vs. 80.8%, respectively; p = 0.135) from the time point of SRS. The overall 1-year survival for ARS and ARD was 79.9 and 86.1%, respectively (p = 0.339). Mean time to progression was 6.45 and 8.0 months and median follow-up was 10 and 15 months for ARS and ARD, respectively. 11.8% of ARS patients and 15.4% of ARD patients developed LMD, p = 0.72. 29.4% of ARS and 48.0% of ARD patients developed DBF, p = 0.145. Our findings suggest that observation after surgical resection, with subsequent treatment with SRS after the development of local failure, may not compromise treatment efficacy. If validated, this would spare patients who do not recur post-surgically from additional treatment.

Breast cancer subtype and stage are prognostic of time from breast cancer diagnosis to brain metastasis development.

Breast cancer brain metastasis (BCBM) is associated with high morbidity and mortality. Patients with breast cancer risk factors associated with rapid development of BCBM could potentially benefit from early brain metastasis screening. We retrospectively reviewed all BCBM patients treated with brain radiotherapy at our institution from 1997 to 2015. Interval time to BCBM was defined as date of pathologic breast cancer diagnosis to date of radiographic evidence of brain metastasis. Patients were stratified by breast cancer molecular subtype and stage at diagnosis. Kaplan Meier analysis was conducted on time to development of BCBM. Breast cancer risk factors were correlated with time to BCBM on Cox proportion hazard analysis. The study cohort comprised 121 BCBM patients, with median interval time to BCBM of 46 months. Times to BCBM for Her2+/2HR+, Her2+, Her2-/HR+, and triple-negative (TNBC) subtypes were 70, 44, 42, and 28 months respectively (p = 0.002). Time to BCBM for stages I, II, III, and IV were 70, 54, 29, and 24 months, respectively (p = 0.000). BCBM patients were further stratified by both molecular subtype (TNBC vs. non-TNBC) and stage (I, II vs. III, IV). Median times to BCBM for non-TNBC/stage I-II, TNBC/stage I-II, non-TNBC stage III-IV, and TNBC/stage III-IV were 68, 47, 29, and 6 months respectively (p = 0.000). Subtype and stage were associated with shorter time to BCBM on multivariate analysis. Subtype and initial stage are independently correlated with decreased time to development of BCBM. Patients with advanced high stage and triple negative breast cancer develop brain metastases significantly earlier.

Breast cancer subtype as a predictor for outcomes and control in the setting of brain metastases treated with stereotactic radiosurgery.

We investigated effects of breast cancer subtype on overall survival (OS), local and distant control, and time from initial diagnosis to brain metastases (BM). We also investigated advances in graded prognostic assessment (GPA) scores. A cohort of 72 patients treated for BM from breast cancer with Gamma Knife stereotactic radiosurgery at our institution from 2000 to 2014 had subtyping available and were used for this study. Median follow up for OS was 12 months and for control was 6 months. OS for luminal, HER2, and triple negative subtypes were 26, 20, and 22 months. OS when stratified by Sperduto et al. (J Clin Oncol 30(4):419-425, 2012) and Subbiah et al. (J Clin Oncol 33(20):2239-2245, 2015) GPAs were similar (p = 0.087 and p = 0.063). KPS and treatment modality were significant for OS (p = 0.002; p = 0.034). On univariate analysis, triple negative subtype and >3 BM were trending and significant for decreased OS (p = 0.084; p = 0.047). On multivariable analysis HER2, triple negative, and >3 BM were significant for OS (p = 0.022; p = 0.040; p = 0.009). Subtype was significant for response on a per lesion basis (p = 0.007). Subtype was trending towards significance when analyzing time from initial diagnosis to BM treatment (p = 0.064). Breast cancer subtype is an important prognostic factor when stratifying breast cancer patients with BM. The addition of number of BM to the GPA is a useful addition and should be further investigated. Subtype has an effect on lesion response, and also on rate of development BM after initial diagnosis.

Outcomes of gamma knife radiosurgery, bi-modality & tri-modality treatment regimens for patients with one or multiple brain metastases: the Columbia University Medical Center experience.

Optimal treatment of brain metastases (BMs) is debatable. However, surgery or gamma knife radiosurgery (GKRS) improves survival when combined with whole brain radiotherapy (WBRT) versus WBRT alone. We retrospectively reviewed an institutional database of patients treated with GKRS for BMs from 1998 to 2013 to explore effects of single or multi-modality therapies on survival. There were 528 patients with median age 62 years. Histologies included 257 lung, 102 breast, 62 melanoma, 40 renal cell, 29 gastrointestinal, and 38 other primary cancers. Treatments included: 206 GKRS alone, 111 GKRS plus WBRT, 109 GKRS plus neurosurgical resection (NSG), and 102 all three modalities. Median overall survival (mOS) was 16.6 months. mOS among patients with one versus multiple metastasis was 17.2 versus 16.0 months respectively (p = 0.825). For patients with one BM, mOS following GKRS alone, GKRS plus WBRT, GKRS plus NSG, and all three modalities was 9.0, 19.1, 25.5, and 25.0 months, respectively, and for patients with multiple BMs, mOS was 8.6, 20.4, 20.7, 24.5 months for the respective groups. Among all patients, multivariate analysis confirmed that tri-modality group had the longest survival (HR 0.467; 95 % CI 0.350-0.623; p < 0.001) compared to GKRS alone; however, this was not significantly different than bi-modality approaches. Uncontrolled primary extra-CNS disease, age and KPS were also independent predictors of survival. Patients treated with GKRS plus NSG, GKRS plus WBRT, or all three modalities had improved OS versus GKRS alone. In our analysis, resection and GKRS allowed avoidance of WBRT without shortening survival.

Site-specific patterns of early-stage cancer diagnosis during the COVID-19 pandemic.

The COVID-19 pandemic caused widespread disruptions in cancer care. We hypothesized that the greatest disruptions in diagnosis occurred in screen-detected cancers. We identified patients (≥18 years of age) with newly diagnosed cancer from 2019 to 2020 in the US National Cancer Database and calculated the change in proportion of early-stage to late-stage cancers using a weighted linear regression. Disruptions in early-stage diagnosis were greater than in late-stage diagnosis (17% vs 12.5%). Melanoma demonstrated the greatest relative decrease in early-stage vs late-stage diagnosis (22.9% vs 9.2%), whereas the decrease was similar for pancreatic cancer. Compared with breast cancer, cervical, melanoma, prostate, colorectal, and lung cancers showed the greatest disruptions in early-stage diagnosis. Uninsured patients experienced greater disruptions than privately insured patients. Disruptions in cancer diagnosis in 2020 had a larger impact on early-stage disease, particularly screen-detected cancers. Our study supports emerging evidence that primary care visits may play a critical role in early melanoma detection.

Updated Analysis of Comparative Toxicity of Proton and Photon Radiation for Prostate Cancer.

PURPOSE: Previous comparative effectiveness studies have not demonstrated a benefit of proton beam therapy (PBT) compared with intensity-modulated radiation therapy (IMRT) for prostate cancer. An updated comparison of GI and genitourinary (GU) toxicity is needed. METHODS: We investigated the SEER-Medicare linked database, identifying patients with localized prostate cancer diagnosed from 2010 to 2017. Procedure and diagnosis codes indicative of treatment-related toxicity were identified. As a sensitivity analysis, we also identified toxicity based only on procedure codes. Patients who underwent IMRT and PBT were matched 2:1 on the basis of clinical and sociodemographic characteristics. We then compared GI and GU toxicity at 6, 12, and 24 months after treatment. RESULTS: The final sample included 772 PBT patients matched to 1,544 IMRT patients. The frequency of GI toxicity for IMRT versus PBT was 3.5% versus 2.5% at 6 months (P = .18), 9.5% versus 10.2% at 12 months (P = .18), and 20.5% versus 23.4% at 24 months (P = .11). The frequency of only procedure codes indicative of GI toxicity for IMRT versus PBT was too low to be reported and not significantly different. The frequency of GU toxicity for IMRT versus PBT was 6.8% versus 5.7% (P = .30), 14.3% versus 12.2% (P = .13), and 28.2% versus 25.8% (P = .21) at 6, 12, and 24 months, respectively. When looking only at procedure codes, the frequency of GU toxicity for IMRT was 1.0% at 6 months, whereas it was too infrequent to report for PBT (P = .64). GU toxicity for IMRT versus PBT was 3.3% versus 2.1% (P = .10), and 8.7% versus 6.7% (P = .10) at 12 and 24 months, respectively. CONCLUSION: In this observational study, there were no statistically significant differences between PBT and IMRT in terms of GI or GU toxicity.

Systematic under-ascertainment of anaplastic large cell lymphoma cases in cancer registries: report from a comprehensive cancer center.

INTRODUCTION: Breast implant-associated anaplastic large cell lymphoma (ALCL) has been rapidly rising in the US and around the world, leading to a mandated "black-box" label on all silicone- and saline-filled implants by the Food and Drug Administration (FDA). Because regulatory decisions in the US and around the world have been influenced primarily by risk estimates derived from cancer registries, it is important to determine their validity in identifying cases of ALCL. METHOD: We reviewed all cases of ALCL submitted to the New York State Cancer Registry from a large comprehensive cancer center in New York City from 2007 to 2019. To determine the possibility of misdiagnosis or under-diagnosis of ALCL cases reported to cancer registries, we accessed the sensitivity and specificity of the ICD-O-3 codes 9714 (ALCL) and 9702 (Mature T-cell lymphoma, not otherwise specified [T-NOS]) to identify pathologically-proven ALCL. RESULTS: We reviewed 2286,164 pathology reports from 47,466 unique patients with primary cancers. Twenty-eight cases of histologically-proven ALCL were identified. The sensitivity and specificity of the ICD-O-3 code 9714 (ALCL) were 82% and 100%, respectively. The sensitivity of the combined codes 9714/9702 (ALCL/T-NOS) was 96% and the specificity was 44%. CONCLUSION: Previous epidemiological studies that influenced regulatory decisions by the FDA may have systematically underestimated the risk of ALCL by at least 20%. We encourage updated global risk estimates of breast ALCL using methods that ensure adequate case ascertainment.

The IDH paradox: Meta-analysis of alkylating chemotherapy in IDH-wildtype and -mutant lower grade gliomas.

BACKGROUND: IDH-wildtype (-wt) status is a pre-requisite for the diagnosis of glioblastoma (GBM); however, IDH-wt gliomas with low grade or anaplastic morphology have historically been excluded from GBM trials and may represent a distinct prognostic entity. While alkylating agent chemotherapy improves overall survival (OS) and progression-free survival (PFS) for IDH-wt GBM and also IDH-mutant gliomas, irrespective of grade, the benefit for IDH-wt diffuse histologic lower grade gliomas is unclear. METHODS: We performed a meta-analysis of randomized clinical trials for World Health Organization (WHO) grade 2-3 gliomas (2009 to present) to determine the effect of alkylating chemotherapy on IDH-wt and -mutant gliomas using a random-effects model with inverse-variance pooling. RESULTS: We identified six trials with 1,204 patients (430 IDH-wt, 774 IDH-mutant) that evaluated alkylating chemoradiotherapy versus radiotherapy alone, allowing us to perform an analysis focused on the value of adding alkylating chemotherapy to radiotherapy. For patients with IDH-wt tumors, alkylating chemotherapy added to radiotherapy was associated with improved PFS (HR:0.77 [95%CI 0.62-0.97], P=.03) but not OS (HR:0.87 [95%CI 0.64-1.18], P=.17). For patients with IDH-mutant tumors, alkylating chemotherapy added to radiotherapy improved both OS (HR:0.52 [95%CI 0.42-0.64], P<.001) and PFS (HR=0.47 [95%CI 0.39-0.57], P<.001) compared to radiotherapy alone. The magnitude of benefit was similar for IDH-mutant gliomas with or without 1p19q-codeletion. CONCLUSIONS: Alkylating chemotherapy reduces mortality by 48% and progression by 53% for patients with IDH-mutant gliomas. Optimal management of IDH-wt diffuse histologic lower grade gliomas remains to be determined, as there is little evidence supporting an OS benefit from alkylating chemotherapy.

National Patterns of Early Adoption of Magnetic Resonance Imaging-Guided Linear Accelerators in 2018 to 2019.

Purpose: Adaptive magnetic resonance imaging-guided linear accelerators (aMRI-LINACs) are an emerging technology with the potential to improve radiation treatment for cancer through improved visualization and adaptive treatment. Given the competing forces of the increased cost, knowledge, and staff required for aMRI-LINAC therapy, it is unpredictable how rapidly and for whom aMRI-LINAC therapy is being adopted. Therefore, given that aMRI-LINAC therapy was granted approval from the Food and Drug Administration in late 2017, we evaluated the National Cancer Database (NCDB) to obtain a nationwide view of early aMRI-LINAC adoption in 2018 to 2019. Methods and Materials: Forty-three disease sites were aggregated. A sample of patients who underwent intensity modulated radiation therapy (IMRT) from 2018 to 2019 were matched 1:1 by stage for the top 4 cancer sites. We then compared 9 characteristics of interest (age, % White [vs non-White], % residing in metro areas, % living in the greatest income quartile, % insured by Medicare, % uninsured or unknown insurance status, % treated at a comprehensive cancer center or academic center, % with no recorded Charlson-Deyo comorbidities, and % residing in an area with highest educational) between the 2 samples (aMRI-LINAC and matched IMRT). Results: Only 171 patients were recorded as having been treated with aMRI-LINACs in the NCDB in 2018 to 2019. Fifty-six percent were male, 89% White, and 54% enrolled in Medicare. The most common sites of disease treated were lung (33 patients), pancreas (30 patients), prostate (29 patients), and breast (23 patients). There were no significant differences between aMRI-LINAC- and IMRT-matched patients except that patients with lung or breast cancer treated with aMRI-LINAC were significantly more likely to be treated at a comprehensive cancer center or academic center. Conclusions: aMRI-LINAC adoption recorded in the NCDB after Food and Drug Administration approval was potentially underreported, slow, and attributed to academic sites of practice. Further longitudinal study will be needed to assess how practice patterns evolve with greater adoption.

Influenza activity and regional mortality for non-small cell lung cancer.

Lung cancer is the leading cause of cancer deaths in the United States and worldwide. While influenza illness is known to be particularly dangerous for frail and elderly patients, the relationship between influenza illness and outcomes in patients with cancer remains largely unknown. The Surveillance, Epidemiology, and End Results (SEER) database was queried to identify patients with non-small cell lung cancer (NSCLC) diagnosed between 2009 and 2015. Influenza-like illness (ILI) activity, provided by the Outpatient Influenza-like Illness Surveillance Network of the Center of Disease for Control and Prevention, was merged with the SEER dataset on the state-month level. Regional monthly mortality rates were compared during low versus high flu months in this ecological cohort study. 202,485 patients with NSCLC from 13 SEER-reporting states were included in the analysis. 53 of 1049 state-months (5.1%) had high flu activity. Monthly mortality rates during low and high flu months were 0.041 (95% CI 0.041-0.042) and 0.051 (95% CI 0.050-0.053), respectively (RR 1.24 [95% CI 1.21-1.27]). The association between ILI activity and mortality was observed at the individual state level and in all clinical and regional subgroups. Increased regional influenza activity is associated with higher mortality rates for patients with NSCLC. Vaccine-directed initiatives and increased awareness amongst providers will be necessary to address the growing but potentially preventable burden of influenza-related lung cancer deaths in the U.S.

MGMT promoter methylation in 1p19q-intact gliomas.

Objective: Standard-of-care for 1p19q-intact anaplastic gliomas is defined by the international randomized phase III CATNON trial, which found an overall survival (OS) benefit for adjuvant temozolomide (TMZ) when added to radiotherapy. Paradoxically, TMZ did not appear to benefit patients with IDH-wildtype gliomas, regardless of MGMT promoter status. The authors concluded that well-powered prospective study on the clinical efficacy of TMZ for patients with IDH-wildtype anaplastic gliomas (meeting criteria for glioblastoma) is warranted. Given that the prognostic and predictive role of MGMT status for grade 2-3 gliomas is unresolved, we determined the effect of MGMT status on OS in patients with 1p19q-intact gliomas in the National Cancer Database (NCDB). Methods: We queried the NCDB from 2018-2019 for patients with IDH-wildtype or -mutant astrocytomas who received chemotherapy with follow-up through 2022. The Kaplan-Meier method and Cox proportional hazards regressions models were used to determine the association of MGMT with OS. Results: We identified 1,514 patients who were newly diagnosed with IDH-wildtype (n = 802, 33% methylated) or - mutant astrocytomas (n = 712, 48% methylated) and received chemotherapy during initial management. An unmethylated promoter was associated with poorer survival in patients with IDH-wildtype (3-year OS 34% [95%CI 29-39%] vs. 46% [95%CI 39-54%], p < .001, adjusted HR 1.53 [95%CI 1.24-1.89]) but not IDH-mutant astrocytomas (3-year OS 79% [95%CI 74-84%] vs. 80% [95%CI 75-86%], p = .81, HR 1.04 [95%CI 0.73-1.50]). Conclusions: This ancillary analysis supports adjuvant TMZ as standard-of-care for anaplastic astrocytomas (IDH-mutant and 1p19q-intact), irrespective of MGMT status. Determining the optimal strategy for diffuse gliomas that are IDH-wildtype will be particularly important. MGMT promoter methylation should be considered as a stratification factor in future clinical trials for these patients.