A systematic review and meta-analysis of pathologic complete response rates for patients with cholangiocarcinoma treated on liver transplant protocols.

BACKGROUND AND OBJECTIVES: Many heterogenous orthotopic liver transplant (OLT) protocols exist for patients with unresectable cholangiocarcinoma. Little is known about the incidence, predictors for, and the significance of achieving a pathologic complete response (pCR). METHODS: We performed a systematic review through September 2022 of the PubMed, Embase, and Web of Science databases. A random-effect meta-analysis was conducted to pool data across studies with reported pCR rates. Heterogeneity between treatment protocols was assessed via subgroup analysis. The pCR and 1-, 3-, and 5-year recurrence-free survival (RFS) and overall survival (OS) rates were extracted as outcomes of interest. RESULTS: A total of 15 studies reported pCR rates and were grouped by use of the Mayo protocol (4/15), stereotactic body radiation therapy (2/15), and an Other category (9/15). The pooled pCR rate among all studies was 32%. Both radiation technique and duration of CHT showed no significant association with pCR (p = 0.05 and 0.13, respectively). Pooled 1-year RFS and OS after any neoadjuvant therapy and OLT was 80% (95% confidence interval [CI], 0.61-0.91), and 91% (95% CI, 0.87-0.94), respectively. There was no 1-year OS difference detected among the three groups. pCR was not associated with OS in the meta-regression. Pooled 3- and 5-year OS among all studies was 72% and 61%, respectively. CONCLUSIONS: The pooled incidence of pCR was 32%. Differences in radiation technique did not appear to influence pCR rates and upon meta-regression, pCR was not a surrogate marker for survival.

Mental health disorders are more common in patients with Hodgkin lymphoma and may negatively impact overall survival.

BACKGROUND: Long-term mental health outcomes were characterized in patients who were diagnosed with Hodgkin lymphoma (HL), and risk factors for the development of mental health disorders were identified. METHODS: Patients who were diagnosed with HL between 1997 and 2014 were identified in the Utah Cancer Registry. Each patient was matched with up to five individuals from a general population cohort identified within the Utah Population Database, a unique source of linked records that includes patient and demographic data. RESULTS: In total, 795 patients who had HL were matched with 3575 individuals from the general population. Compared with the general population, patients who had HL had a higher risk of any mental health diagnosis (hazard ratio, 1.77; 95% confidence interval, 1.57-2.00). Patients with HL had higher risks of anxiety, depression, substance-related disorders, and suicide and intentional self-inflicted injuries compared with the general population. The main risk factor associated with an increased risk of being diagnosed with mental health disorders was undergoing hematopoietic stem cell transplantation, with a hazard ratio of 2.06 (95% confidence interval, 1.53-2.76). The diagnosis of any mental health disorder among patients with HL was associated with a detrimental impact on overall survival; the 10-year overall survival rate was 70% in patients who had a mental health diagnosis compared with 86% in those patients without a mental health diagnosis (p < .0001). CONCLUSIONS: Patients who had HL had an increased risk of various mental health disorders compared with a matched general population. The current data illustrate the importance of attention to mental health in HL survivorship, particularly for patients who undergo therapy with hematopoietic stem cell transplantation.

Near Complete Response to Trametinib Treatment in Histiocytic Sarcoma Harboring a Somatic KRAS Mutation.

Survival outcomes of patients with histiocytic neoplasms are poor, with no standard-of-care treatments available for these malignancies. Recent characterization of the genomic landscape of various histiocytic neoplasms have shown a predominance of activating driver mutations within the MAPK/ERK pathway (ie, BRAF, MEK, KRAS, MAPK, and NRAS). Subsequently, successful treatment of these malignancies with BRAF and MEK inhibitors has been reported. This report presents the first patient with histiocytic sarcoma harboring a somatic KRAS Q61H mutation who was subsequently treated to a near complete response with the MEK inhibitor trametinib. Due to patient preference, lack of standard of care treatments, and associated morbidity from head and neck dissection, initial disease reduction provided by trametinib therapy allowed for a less morbid resection. This case report highlights the utility of up-front next-generation sequencing and the efficacy of MEK inhibition in patients with histiocytic sarcoma harboring activating KRAS mutations.

NCCN Guidelines® Insights: Hodgkin Lymphoma, Version 2.2022.

Hodgkin lymphoma (HL) is an uncommon malignancy of B-cell origin. Classical HL (cHL) and nodular lymphocyte-predominant HL are the 2 main types of HL. The cure rates for HL have increased so markedly with the advent of modern treatment options that overriding treatment considerations often relate to long-term toxicity. These NCCN Guidelines Insights discuss the recent updates to the NCCN Guidelines for HL focusing on (1) radiation therapy dose constraints in the management of patients with HL, and (2) the management of advanced-stage and relapsed or refractory cHL.

Refusal of Local Therapy in Esophageal Cancer and Impact on Overall Survival.

OBJECTIVE: The aim of this study was to understand factors associated with refusal of local therapy in esophageal cancer and compare the overall survival (OS) of patients who refuse therapies with those who undergo recommended treatment. METHODS: National Cancer Database data for patients with non-metastatic esophageal cancer from 2006 to 2013 were pooled. T1N0M0 tumors were excluded. Pearson's Chi-square test and multivariate logistic regression analyses were used to assess demographic, clinical, and treatment factors. After propensity-score matching with inverse probability of treatment weighting, OS was compared between patients who refused therapies and those who underwent recommended therapy, using Kaplan-Meier analyses and doubly robust estimation with multivariate Cox proportional hazards modeling. RESULTS: In total, 37,618 patients were recommended radiation therapy (RT) and/or esophagectomy; we found 1403 (3.7%) refused local therapies. Specifically, 890 of 18,942 (4.6%) patients refused surgery and 667 of 31,937 (2.1%) refused RT. Older patients, females, those with unknown lymphovascular space invasion, and those uninsured or on Medicare were more likely to refuse. Those with squamous cell carcinoma, N1 disease, higher incomes, living farther from care, and those who received chemotherapy were less likely to refuse. Five-year OS was decreased in patients who refused (18.1% vs. 27.6%). The survival decrement was present in adenocarcinoma but not squamous cell carcinoma. In patients who received surgery or ≥ 50.4 Gy RT, there was no OS decrement to refusing the other therapy. CONCLUSIONS: We identified characteristics that correlate with refusal of local therapy. Refusal of therapy was associated with decreased OS. Patients who received either surgery or ≥ 50.4 Gy RT had no survival decrement from refusing the opposite modality.

The Effect of Measured Radiotherapy Dose on Intrathecal Drug Delivery System Function.

OBJECTIVES: Radiation therapy (RT) and intrathecal drug delivery systems (IDDS) are often used concurrently to optimize pain management in patients with cancer. Concern remains among clinicians regarding the potential for IDDS malfunction in the setting of RT. Here we assessed the frequency of IDDS malfunction in a large cohort of patients treated with RT. MATERIALS AND METHODS: Cancer patients with IDDS and subsequent RT at our institution from 2011 to 2019 were eligible for this study. Patients were excluded in the rare event that their IDDS was managed by an outside clinic and follow-up documentation was unavailable. Eighty-eight patients aged 22-88 years old (43% female, 57% male) representing 106 separate courses of RT were retrospectively identified. Patients received varying levels of radiation for treatment of cancer and cumulative dose to the IDDS was calculated. IDDS interrogation was subsequently performed by a pain specialist. Malfunction was recorded as deviation from the expected drug volume and/or device errors reported upon interrogation as defined by the manufacturer. RESULTS: Total measured RT dose to the IDDS ranged from 0 to 18.0 Gy (median = 0.2 Gy) with median dose of 0.04 Gy/fraction (range, 0-3.2 Gy/fraction). Ten pumps received a total dose >2 Gy and three received ≥5 Gy. Eighty-two percentage of patients had follow-up with a pain specialist for IDDS interrogation and all patients underwent follow-up with a healthcare provider following RT. There were zero incidences of IDDS malfunction related to RT. No patient had clinical evidence of radiation related pump malfunction at subsequent encounters. CONCLUSIONS: We found no evidence that RT in patients with IDDS led to device failure or dysfunction. While radiation oncologists and pain specialists should coordinate patient care, it does not appear that RT dose impacts the function of the IDDS to warrant significant clinical concern.

Hodgkin Lymphoma, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology.

The NCCN Clinical Practice Guidelines in Oncology for Hodgkin Lymphoma (HL) provide recommendations for the management of adult patients with HL. The NCCN panel meets at least annually to review comments from reviewers within their institutions, examine relevant data, and reevaluate and update their recommendations. Current management of classic HL involves initial treatment with chemotherapy alone or combined modality therapy followed by restaging with PET/CT to assess treatment response. Overall, the introduction of less toxic and more effective regimens has significantly advanced HL cure rates. This portion of the NCCN Guidelines focuses on the management of classic HL.

NCCN Guidelines Insights: Hodgkin Lymphoma, Version 1.2018.

The NCCN Clinical Practice Guidelines in Oncology for Hodgkin Lymphoma (HL) provide recommendations for the management of adult patients with HL. The NCCN Guidelines Panel meets at least annually to review comments from reviewers within the NCCN Member Institutions, examine relevant data, and reevaluate and update the recommendations. These NCCN Guidelines Insights summarize recent updates centered on treatment considerations for relapsed/refractory classic HL.

Sirt3-mediated deacetylation of evolutionarily conserved lysine 122 regulates MnSOD activity in response to stress.

Genetic deletion of the mitochondrial deacetylase sirtuin-3 (Sirt3) results in increased mitochondrial superoxide, a tumor-permissive environment, and mammary tumor development. MnSOD contains a nutrient- and ionizing radiation (IR)-dependent reversible acetyl-lysine that is hyperacetylated in Sirt3⁻/⁻ livers at 3 months of age. Livers of Sirt3⁻/⁻ mice exhibit decreased MnSOD activity, but not immunoreactive protein, relative to wild-type livers. Reintroduction of wild-type but not deacetylation null Sirt3 into Sirt3⁻/⁻ MEFs deacetylated lysine and restored MnSOD activity. Site-directed mutagenesis of MnSOD lysine 122 to an arginine, mimicking deacetylation (lenti-MnSOD(K122-R)), increased MnSOD activity when expressed in MnSOD⁻/⁻ MEFs, suggesting acetylation directly regulates function. Furthermore, infection of Sirt3⁻/⁻ MEFs with lenti-MnSOD(K122-R) inhibited in vitro immortalization by an oncogene (Ras), inhibited IR-induced genomic instability, and decreased mitochondrial superoxide. Finally, IR was unable to induce MnSOD deacetylation or activity in Sirt3⁻/⁻ livers, and these irradiated livers displayed significant IR-induced cell damage and microvacuolization in their hepatocytes.

Multiagent induction chemotherapy followed by chemoradiation is associated with improved survival in locally advanced pancreatic cancer.

BACKGROUND: The role of chemoradiotherapy (CRT) in locally advanced pancreatic cancer (LAPC) is uncertain after multiple randomized clinical trials have yielded mixed results. The authors used the National Cancer Data Base (NCDB) to determine whether CRT yields a survival benefit compared with chemotherapy alone (CT). METHODS: Patients with nonmetastatic LAPC diagnosed during 2004 through 2014 were identified in the NCDB. Patients who received CT were compared with those who received CRT using chi-square analysis. Univariate and multivariate Cox regression analyses were used to compare demographic, clinical, and treatment characteristics that were predictive of survival. Propensity score matching and shared frailty analysis were done. Subgroup analyses were undertaken to examine patients who underwent pancreatectomy and cohorts of patients who received different CT or CRT regimens. RESULTS: In total, 8689 patients with LAPC were identified. CRT was associated with improved survival (median survival [MS], 13.5 months) compared with CT (MS, 10.6 months) on multivariate analysis (hazard ratio [HR], 0.80; P < .001). Induction chemotherapy before CRT (HR, 0.67; P < .001) and multiagent chemotherapy (HR, 0.72; P < .001) were also identified as independent predictors of survival compared with concurrent CRT and single-agent CT, respectively. Patients in the CRT group who received multiagent induction chemotherapy had superior MS and pancreatectomy rates (MS, 17.5 months; HR, 0.70; P < .001; pancreatectomy rate, 10%) compared with those who received multiagent CT alone (MS, 12.4 months; pancreatectomy rate, 3.3%). Patients who underwent pancreatectomy experienced improved survival (MS, 22 vs 10.6 months; HR, 0.39; P < .001). CONCLUSIONS: In this NCDB analysis, maximizing systemic chemotherapy before CRT improved survival compared with CT alone in patients with LAPC. Continued analysis of CRT in properly selected patients after maximized systemic therapy is needed. Cancer 2017;123:3816-24. © 2017 American Cancer Society.

Local therapy reduces the risk of liver failure and improves survival in patients with intrahepatic cholangiocarcinoma: A comprehensive analysis of 362 consecutive patients.

BACKGROUND: Treatment methods for intrahepatic cholangiocarcinoma (ICC) have improved, but their impact on outcome remains unclear. We evaluated the outcomes of patients definitively treated with resection, radiation, and chemotherapy for ICC, stratified by era. METHODS: Clinico-pathologic characteristics, cause of death, disease-specific survival (DSS), and intrahepatic progression-free survival (IPFS) were compared among patients who underwent resection, radiation, or chemotherapy as definitive treatment strategies for ICC (without distant organ metastasis) between 1997 and 2015. Variables were also analyzed by era (1997-2006 [early] or 2007-2015 [late]) within each group. RESULTS: Among 362 patients in our cohort, 122 underwent resection (early, 38; late, 84), 85 underwent radiation (early, 17; late, 68), and 148 underwent systemic chemotherapy alone (early, 51; late, 97) as definitive treatment strategies, and 7 patients received best supportive care. In the resection group, the 3-year DSS rate was 58% for the early era and 67% for the late era (P = .036), and the 1-year IPFS was 50% for the early era and 75% for the late era (P = .048). In the radiation group, the 3-year DSS was 12% for the early era and 37% for the late era (P = .048), and the 1-year IPFS was 48% for the early era and 64% for the late era (P = .030). In the chemotherapy group, DSS and IPFS did not differ by era. Patients treated with chemotherapy developed liver failure at the time of death significantly more frequently than patients treated with resection (P < .001) or radiation (P < .001). Multivariable analysis identified local therapy (resection or radiation) as a sole predictor of death without liver failure. CONCLUSION: Survival outcomes have improved for local therapy-based definitive treatment strategies for ICC, which may be attributable to maintaining control of intrahepatic disease, thereby reducing the occurrence of death due to liver failure. Cancer 2017;123:1354-1362. © 2016 American Cancer Society.

Chemoradiation Therapy for Unresected Extrahepatic Cholangiocarcinoma: A Propensity Score-Matched Analysis.

BACKGROUND: Unresected extrahepatic cholangiocarcinoma (uEHCC) remains a deadly disease. Guidelines for uEHCC recommend either chemotherapy alone (CT) or chemoradiotherapy (CRT). This study used the National Cancer Database (NCDB) to compare outcomes for patients treated with CT and those who underwent CRT. METHODS: Patients with initially diagnosed non-metastatic uEHCC from 2004 to 2014 were identified. Using Chi square analysis, patients who underwent CT were compared with those who received CRT. Uni- and multivariate Cox regression analyses were used to compare characteristics related to survival. Propensity score matching and shared frailty analysis were undertaken to correct for baseline differences between the two groups. Additional analyses were performed to compare survival for the minority of patients who underwent surgery and advanced-stage patients. RESULTS: The study identified 2996 patients with uEHCC. Chemoradiation was associated with better survival (median survival [MS], 14.5 months; hazard ratio [HR] 0.84; p < 0.001) than CT alone (MS, 12.6 months). Induction of CT before CRT was associated with a trend toward decreased risk of death compared with concurrent CRT (HR 0.81; p = 0.051). For the patients able to undergo surgery after initial treatment, MS was 24.5 months (HR 0.38; p < 0.001) versus 12.2 months for those who had no surgery. For these patients, CRT also was associated with better survival (MS, 31.2 months; HR 0.66; p = 0.001) than CT (MS, 22.1 months). Positive margins at surgery yielded survival equivalent to that with no surgery. CONCLUSION: Although CRT may be associated with slightly better survival in uEHCC than CT alone, the majority of the benefit was observed for patients able to undergo eventual surgery.

Interstitial Brachytherapy for the Treatment of Locally Recurrent Anorectal Cancer.

BACKGROUND: Local tumor control (LC), overall survival (OS), symptom palliation, and late toxicity for patients with locally recurrent anorectal cancer treated with a computed tomography (CT)-guided interstitial brachytherapy implant were examined. METHODS: The medical records of 20 consecutive patients who had received interstitial brachytherapy for locally recurrent anorectal cancer from 2000 through 2012 were reviewed. Seventeen patients (85 %) had rectal cancer and three had anal cancer [median follow-up time for living patients, 23 months (range 13-132)]. Brachytherapy was used most commonly at the second pelvic recurrence (n = 13, 65 %). The implant dose was prescribed to 80 Gy to a 1-cm margin or 120 Gy to 100 % of the gross tumor volume. Endpoints were OS, LC, toxicity, and symptom palliation rate, all calculated from the time of implant. RESULTS: The actuarial 1-year rates of LC and OS were 80 and 95 %, respectively. At presentation, 17 patients (85 %) had symptoms related to the treated tumor which were palliated in 13 patients (76 %) at a median time of 3 months (range 1-6); palliation was permanent for seven patients (54 %), and the other six patients lost palliation after a median 8 months (range 5-17). One patient experienced a grade 3 late complication requiring a stent for hydronephrosis; five had grade 2 toxicity, and four had grade 1 toxicity. CONCLUSIONS: CT-guided interstitial brachytherapy for locally recurrent anorectal tumors produced durable tumor control and long-term survival, with effective palliation and minimal long-term morbidity.

Survival Outcomes of Limited-Stage Diffuse Large B-Cell Lymphoma Treated With Radiation Therapy.

BACKGROUND: Patients with favorable risk limited-stage (LS) diffuse large b-cell lymphoma (DLBCL) have shown excellent outcomes without radiotherapy (RT). However, the role of RT for the remainder of LS-DLBCL patients is less well defined. We aimed to investigate whether the addition of RT provided an overall survival (OS) benefit in a real-world cohort of LS-DLBCL patients based on primary site at presentation. MATERIALS AND METHODS: Retrospective data from 39,745 patients with stage I and II DLBCL treated with front-line combination chemotherapy alone or followed by RT were identified using the National Cancer Database from 2004 to 2015. RESULTS: The addition of RT was associated with improved 5-year OS for all LS patients as compared to those treated with chemotherapy alone (85% vs. 80%, P < .001). RT was associated with improved 5-year OS in both the nodal and extranodal disease patients (nodal: 85% vs. 80%, P < .001; extranodal: 83% vs. 79%; P < .001). Extranodal sites with prolonged OS from the addition of RT include skin and soft tissue, head and neck, testicular, and thyroid sites (all P < .02). Breast, bone, lung and gastrointestinal extranodal primary sites had no OS benefit from the inclusion of RT. In multivariate analysis, the addition of RT was an independent factor for improved survival for all LS patients ([HR] 0.84, 95% [CI] 0.81-0.88; P < .001). CONCLUSION: Though there is no consensus on optimal treatment indications for RT in LS-DLBCL, these data suggest certain subgroups may have benefit when RT is added to front-line chemotherapy.

Incident diabetes among older Asian, Native Hawaiian, and Pacific Islander women with breast cancer.

BACKGROUND: The risk of diabetes among Asian, Native Hawaiian, and Pacific Islander (ANHPI) women after breast cancer is unclear. This study estimated the risk of incident type II diabetes in older ANHPI and older non-Hispanic White (NHW) women with breast cancer from the US National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Medicare linked claims. METHODS: A matched cohort of 7122 older ANHPI and 21 365 older NHW women with breast cancer were identified from SEER-Medicare between 2000 and 2017. To assess the risk of incident type II diabetes after breast cancer, hazard ratios (HRs) and 95% confidence intervals (95% CI) were estimated using the Cox proportional-hazards regression model. RESULTS: During the mean 8 years of follow-up, 9.3% of older women with breast cancer developed incident type II diabetes. In comparison with older NHW women, older ANHPI women without a known history of diabetes had an elevated risk of diabetes after breast cancer, with strong associations observed for Pacific Islander (HR = 3.09, 95% CI = 1.43 to 6.67), Vietnamese (HR = 2.12, 95% CI = 1.33 to 2.36), and Filipino (HR = 2.02, 95% CI = 1.57 to 2.59) women with breast cancer, adjusting for potential confounders. Among ANHPI women with breast cancer, more baseline comorbidities and obesity were risk factors for developing incident type II diabetes. CONCLUSION: ANHPI women diagnosed with breast cancer had an elevated risk of type II diabetes compared with older NHW women with breast cancer. Routine monitoring and management of diabetes are warranted in older ANHPI women with breast cancer.

Incident Cardiovascular Disease Risk among Older Asian, Native Hawaiian and Pacific Islander Breast Cancer Survivors.

BACKGROUND: Cardiotoxicity among breast cancer survivors is associated with chemotherapy and radiation therapy. The risk of cardiovascular disease (CVD) among Asian, Native Hawaiian and Pacific Islander (ANHPI) breast cancer survivors in the United States is unknown. METHODS: We used the SEER-Medicare linked database to estimate the risk of CVD among older breast cancer survivors. International Classification of Disease diagnosis codes were used to identify incident CVD outcomes. Cox proportional hazards models were used to estimate HRs and 95% confidence intervals (CI) comparing ANHPI with Non-Hispanic White (NHW) patients with breast cancer for CVD, and among ANHPI race and ethnicity groups. RESULTS: A total of 7,122 ANHPI breast cancer survivors and 21,365 NHW breast cancer survivors were identified. The risks of incident heart failure and ischemic heart disease were lower among ANHPI compared with NHW breast cancer survivors (HRheart failure, 0.72; 95% CI, 0.61-0.84; HRheart disease, 0.74; 95% CI, 0.63-0.88). Compared with Japanese patients with breast cancer, Filipino, Asian Indian and Pakistani, and Native Hawaiian breast cancer survivors had higher risks of heart failure. ischemic heart disease and death. Among ANHPI breast cancer survivors, risk factors for heart failure included older age, higher comorbidity score, distant cancer stage and chemotherapy. CONCLUSIONS: Our results support heterogeneity in CVD outcomes among breast cancer survivors among ANHPI race and ethnicity groups. Further research is needed to elucidate the disparities experienced among ANHPI breast cancer survivors. IMPACT: Filipino, Asian Indian and Pakistani, and Native Hawaiian patients with breast cancer had higher risks of heart failure, ischemic heart disease and death among ANHPI patients with breast cancer.

Neoadjuvant Therapy Regimens for Hilar Cholangiocarcinoma Before Liver Transplant.

OBJECTIVES: Patients with unresectable hilar cholangiocarcinoma (hCCA) may be eligible for curative treatment through liver transplantation (LT). Neoadjuvant protocols often include radiotherapy (RT), however, there is no standard RT approach. The purpose of this study is to characterize practice patterns of RT use before transplantation for hCCA. METHODS: A survey was administered to radiation oncologists practicing at LT centers identified through the U.S. Organ Procurement and Transplant Network and the International Cholangiocarcinoma Research Network. The survey consisted of 13 questions regarding RT details as well as approaches to systemic therapy. For cross-regimen comparison, the cumulative RT tumor dose was standardized using the EQD2 method. RESULTS: Twenty-three centers utilizing neoadjuvant therapy for hCCA were identified. Most respondents (96%) use both chemotherapy and RT as part of their protocol. Elective nodal volumes commonly included the portal vein lymph nodes (91%) and celiac artery lymph nodes (70%). After an initial 45 Gy plan, a wide range of sequential boost regimens was used. The median cumulative dose including boosts to the gross disease was 58 Gy (EQD2) with a wide range of 40 to 110 Gy. Five (22%) include brachytherapy as part of their treatment plan. The majority (96%) used concurrent chemotherapy with fluoropyrimidines. CONCLUSIONS: These results suggest significant variability of neoadjuvant RT use for hCCA before LT. A wide range of doses and fractionation schemes are utilized with cumulative doses ranging from 40 to 110 Gy (EQD2). A further study evaluating the efficacy and toxicity of these various approaches is warranted to better inform best practices.

The Implications of Treatment Delays in Adjuvant Therapy for Resected Cholangiocarcinoma Patients.

PURPOSE: The purpose of this study is to understand factors associated with timing of adjuvant therapy for cholangiocarcinoma and the impact of delays on overall survival (OS). METHODS: Data from the National Cancer Database (NCDB) for patients with non-metastatic bile duct cancer from 2004 to 2015 were analyzed. Patients were included only if they underwent surgery and adjuvant chemotherapy and/or radiotherapy (RT). Patients who underwent neoadjuvant or palliative treatments were excluded. Pearson's chi-squared test and multivariate logistic regression analyses were used to assess the distribution of demographic, clinical, and treatment factors. After propensity score matching with inverse probability of treatment weighting, OS was compared between patients initiating therapy past various time points using Kaplan Meier analyses and doubly robust estimation with multivariate Cox proportional hazards modeling. RESULTS: In total, 7,733 of 17,363 (45%) patients underwent adjuvant treatment. The median time to adjuvant therapy initiation was 59 days (interquartile range 45-78 days). Age over 65, black and Hispanic race, and treatment with RT alone were associated with later initiation of adjuvant treatment. Patients with larger tumors and high-grade disease were more likely to initiate treatment early. After propensity score weighting, there was an OS decrement to initiation of treatment beyond the median of 59 days after surgery. CONCLUSIONS: We identified characteristics that are related to the timing of adjuvant therapy in patients with biliary cancers. There was an OS decrement associated with delays beyond the median time point of 59 days. This finding may be especially relevant given the treatment delays seen as a result of COVID-19.

Secondary malignancies in non-Hodgkin lymphoma survivors: 40 years of follow-up assessed by treatment modality.

BACKGROUND: Survivors of non-Hodgkin lymphoma (NHL) have increased secondary malignancy (SM) risk. We quantified this risk by patient and treatment factors. METHODS: Standardized incidence ratios (SIR, observed-to-expected [O/E] ratio) were assessed in 142,637 NHL patients diagnosed from 1975 to 2016 in the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Comparisons were made between subgroups in terms of their SIRs relative to respective endemic populations. RESULTS: In total, 15,979 patients developed SM, more than the endemic rate (O/E 1.29; p < 0.05). Compared with white patients, relative to respective endemic populations, ethnic minorities had a higher risk of SM (white O/E 1.27, 95% CI 1.25-1.29; black O/E 1.40, 95% CI 1.31-1.48; other O/E 1.59, 95% CI 1.49-1.70). Relative to respective endemic populations, patients who received radiotherapy had similar SM rates to those who did not (O/E 1.29 each), but irradiated patients had increased breast cancer (p < 0.05). Patients who received chemotherapy had higher SM rates than those who did not (O/E 1.33 vs. 1.24, p < 0.05) including more leukemia, Kaposi sarcoma, kidney, pancreas, rectal, head and neck, and colon cancers (p < 0.05). CONCLUSIONS: This is the largest study to examine SM risk in NHL patients with the longest follow-up. Treatment with radiotherapy did not increase overall SM risk, while chemotherapy was associated with a higher overall risk. However, certain subsites were associated with a higher risk of SM, and they varied by treatment, age group, race and time since treatment. These findings are helpful for informing screening and long-term follow-up in NHL survivors.