Analysis Of Cause-specific Survival Research Articles

Survival trends for left and right sided colon cancer using the population-based SEER database: A 45-year analysis from 1975 to 2019.

e15560 Background: Survival differences between left sided (LCC) and right sided colon cancer (RCC) have been previously reported with mixed results. Many used short study periods and did not account for "other cause of mortality" (OCM). The differences in survival may exist irrespective of modern therapeutic agents, with implications for future clinical trial designs. Methods: We sought to assess the trends in the cause- specific and overall survival of colon cancer based on sidedness, using competing risk analysis. A SEER database from 1975 to 2019 was used.Time interval chosen based on clinical adoption of modern chemotherapy (1975-1989 = period A, 1990-2004 = B, 2005-2019 = C). Cox model was used for overall survival (OS), and Fine-Gray competing risk analysis for cause-specific survival (CSS). Adenocarcinoma were included, and primary rectal cancers excluded. Results: Of the 227,637 colon cancer patients, 50.1% were female and 46.2% RCC. Racial distribution of LCC vs RCC; Black-48.5% vs 51.5%, White-53.1% vs 46.9%, API/AN-63.7% vs 36.3%; p < 0.001. Age ≥ 65 were more likely to have RCC vs LCC (51.4% vs 48.6%), LCC common for age 18-49 (64.6% vs 35.4%), 50-64 (62.3% vs 37.7%), p < 0.00l. Females more likely to have RCC (50.4%vs 41.9%; p < 0.001), and males to have LCC (58.1% vs 49.6%;p < 0.001). Median CSS for LCC and RCC was 19.3 and 16.7 years respectively for 1975-1989 but median CSS for period B and C did not reach during study period. Median OS increased over time for both LCC (A = 5.5 yrs.; B = 7.6yrs and C = 10.5 yrs.) and RCC (4.3, 5.8 and 7.5yrs respectively). CSS was better for LCC than RCC for period C (aHR 0.89; 0.86-0.92; p < 0.001). LCC consistently showed superior OS for all study periods. Stage stratification showed worse CSS for localized and regional LCC in the earlier study periods, but the risk attenuated over time. However, left sided distant disease had superior CSS for all periods. Overall survival was better for LCC irrespective of stage, with gradual improvement over time(table 1). Conclusions: Over the past four decades, LCC has shown superior survival over right sided tumors. Furthermore, prognosis between LCC and RCC became more divergent in favor of LCC with the adoption of modern chemotherapy. Clinical trials for colon cancer should consider sidedness when recruiting patients for intervention. [Table: see text]

Incidence, epidemiological characteristics, and cause-specific survival analysis of ampullary carcinoma using the SEER database.

4168 Background: Ampullary carcinomas (AC) are rare and comprise only 0.2% of gastrointestinal malignancies, and there is a paucity of studies analyzing them. We studied the incidence, demographics, tumor characteristics, and survival variables of patients with AC using the Survival, Epidemiology, and End Results [SEER] November 2021 database. Methods: We identified 3650 patients aged >18 with microscopically confirmed adenocarcinoma of the ampulla using ICD-O-3 site code C241 and histology codes (8140-8147, 8480, 8490, 8500). The epidemiological characteristics and the survival variables included were age, gender, ethnicity, and American Joint Committee on Cancer [AJCC] Staging. The overall 5-year survival (OS), cause-specific 5-year survival (CSS), and CSS plots across different strata were plotted using the Kaplan-Meier Method. The analysis was done using the Cox proportional hazard regression model (p<0.05). Results: The overall age-adjusted incidence of AC was 0.3 per 100,000 cases. The median age at diagnosis was 69 (Interquartile range - 59, 78). It was more common in males (56.03%) and Non-Hispanic White (58.96 %), with the most common stages at a presentation being stage 2B IIB (22.08%) and stage III (22.11%). The observed overall 5-year survival was 31%, and the cause-specific 5-year survival was 37.5%. The CSS was not significantly associated with gender (p=0.06). The estimated hazards of death attributed to AC increase by 13% (p < 0.0001) for every 10-year increase in age at diagnosis above 67 years. The CSS was also associated with race, with African Americans and Hispanics being associated with higher hazards of death attributed to AC when compared to Non-Hispanic Whites with HR of 1.5 (p<0.0001) and 1.12 (p=0.01), respectively. Conclusions: Ampullary carcinoma is more commonly seen in males and non-Hispanic Whites with a median age of 69 years. Patients are typically diagnosed in stages IIB and III. Lower CSS rates were associated with advancing age, African American, and Hispanic populations. We need further studies to determine whether these disparities between different races are due to socioeconomic, genetic, or biological factors. Additional studies investigating how different treatment options affect AC survival, especially in this population subset, can be explored. [Table: see text]

Effect of radiation exposure on survival after first solid cancer diagnosis in A-bomb survivors

BackgroundComparison of the estimated effect of atomic bomb radiation exposure on solid cancer incidence and solid cancer mortality in the RERF Life Span Study (LSS) reveals a difference in the magnitude and shape of the excess relative risk dose response. A possible contributing factor to this difference is pre-diagnosis radiation effect on post-diagnosis survival. Pre-diagnosis radiation exposure theoretically could influence post-diagnosis survival by affecting the genetic makeup and possibly aggressiveness of cancer, or by compromising tolerance for aggressive treatment for cancer. MethodsWe analyze the radiation effect on post-diagnosis survival in 20,463 LSS subjects diagnosed with first-primary solid cancer between 1958 and 2009 with particular attention to whether death was caused by the first-primary cancer, other cancer, or non-cancer diseases. ResultsFrom multivariable Cox regression analysis of cause-specific survival, the excess hazard at 1 Gy (EH1Gy) for death from the first primary cancer was not significantly different from zero – p = 0.23, EH1Gy = 0.038 (95 % CI: −0.023, 0.104). Death from other cancer and death from non-cancer diseases both were significantly associated with radiation dose: other cancer EH1Gy = 0.38 (95 % CI: 0.24, 0.53); non-cancer EH1Gy = 0.24 (95 % CI: 0.13, 0.36), both p < 0.001. ConclusionThere is no detectable large effect of pre-diagnosis radiation exposure on post-diagnosis death from the first primary cancer in A-bomb survivors. ImpactA direct effect of pre-diagnosis radiation exposure on cancer prognosis is ruled out as an explanation for the difference in incidence and mortality dose response in A-bomb survivors.

Psychiatric care following deliberate self-harm and prospective mortality: evidence from a national cohort of patients in routine care

IntroductionPsychiatric care following self-harm treatment is pivotal in patients´ life both in short- and long-terms.ObjectivesTo examine follow-up psychiatric care received by patients treated for deliberate self-harm (DSH), and to assess the influence of psychiatric referral and treatment attendance on risk for subsequent mortality.MethodsNationwide registries were interlinked to follow all DSH patients for data on personal socioeconomic status, clinical features of DSH, psychiatric treatment and cause of death. Data were analyzed with Logistic regression and cause-specific survival analysis.Results The study identified 43153 patients involving 69569 DSH episodes. Of these patients 15.7% were referred or transferred to psychiatric services and 51.0% attended psychiatric treatment within subsequent 3 months. Evidently, prior psychiatric history and psychiatric comorbidities had strong influence on both referral and attendance to psychiatric healthcare, personal socioeconomic status also deviated the likelihoods. During the follow-up, 7041 patients died from suicide (n=911) or other causes (n=6130). While suicide risk was highly associated with male gender, middle age, and particularly, prior and coexisting psychopathologies, other cause mortality was strongly associated with old age and socioeconomic disadvantages. Meanwhile, a referral to psychiatric services was associated with suicide risk, and the risk was particularly high for patients who received the referral but did not attend psychiatric treatment. The observed effect was more pronounced during the early years, and in patients of young or middle age and those with a clear intent of self-harm.ConclusionsThe insightful findings highlight the importance of patients´ attendance and engagement in follow-up psychiatric care on risk for subsequent mortality.DisclosureNo significant relationships.

Association of Psychiatric Services Referral and Attendance Following Treatment for Deliberate Self-harm With Prospective Mortality in Norwegian Patients

Psychiatric care following somatic treatment for deliberate self-harm (DSH) is pivotal in patients' lives both in the short and long term, but evidence to guide such care is limited. To examine follow-up psychiatric care for patients treated for DSH (ie, intentional self-injury or self-poisoning, irrespective of motivation) at hospital emergency departments and to assess the association of psychiatric referral and treatment attendance with risk of subsequent mortality in these patients. Retrospective data from several Norwegian registries were interlinked to follow up a national cohort of all patients with hospital-treated DSH for up to 11 years from 2008 through 2018. Data were analyzed from March to October 2021. Socioeconomic characteristics, psychiatric history, and clinical features of DSH. Referral to psychiatric services, attendance in psychiatric treatment, and prospective mortality were the 3-stage outcomes during follow-up. Logistic regression with odds ratios and cause-specific survival analysis with hazard ratios were used to examine associations between exposures and outcomes. The study identified 43 153 patients (24 286 [56.3%] female; median [IQR] age at index DSH, 39.0 [23.0-56.0] years) involving 69 569 DSH episodes. Of these patients, 6762 (15.7%) were referred to psychiatric services after somatic treatment for DSH, and 22 008 patients (51.0%) attended psychiatric treatment within 3 months of discharge following somatic treatment for DSH. Prior psychiatric history and psychiatric disorders comorbid with DSH were associated with both referral to and attendance in psychiatric care. During follow-up, 7041 patients died by suicide (n = 911) or other causes (n = 6130). While suicide risk was associated with male sex, age 35 to 64 years, and particularly prior and coexisting psychopathologies, other-cause mortality was associated with age 65 years and older and socioeconomic disadvantage. Patients with psychiatric referrals generally had an increased risk of suicide, but the risk was particularly high among patients who received a referral but did not subsequently attend psychiatric treatment (adjusted hazard ratio, 3.07; 95% CI, 2.28-4.12). The observed association was more pronounced during the first years of follow-up and in patients aged 10 to 34 years or 35 to 64 years and those with a clear intent of self-harm. This national cohort study found an association between psychiatric care attendance following treatment for DSH and prospective mortality, highlighting the importance of patient engagement in psychiatric treatment.

Trends in Adjuvant External Beam Radiation Therapy for Nonanaplastic Thyroid Cancer in California, 2003-2017

BackgroundExternal beam radiation therapy (EBRT) is rarely used to treat patients with differentiated or medullary thyroid cancer. Although EBRT is generally administered to patients with high-risk or unresectable diseases, neither its indications for the use nor the associated outcomes are well-defined. We used a statewide cohort to assess the trends in EBRT use and postradiation outcomes in California. MethodsA population-based study of patients within the California Cancer Registry who underwent EBRT after surgery for nonanaplastic thyroid cancer (2003-2017) was conducted. The primary outcome was the annual utilization rate of EBRT. The secondary outcomes included Kaplan-Meier analysis for cause-specific survival and identifying factors associated with improved survival after EBRT. ResultsAmong the 57 607 patients with nonanaplastic thyroid cancer from 2003 to 2017, 344 (0.6%) patients received EBRT. EBRT was utilized in 0.4% of papillary, 1.1% of follicular, and 7.7% of medullary thyroid cancers in California. Overall, 99 (28.8%) patients treated with EBRT died of thyroid cancer. The 10-year cause-specific survival of all patients with thyroid cancer after EBRT was 61.5% (95% CI: 54.8%-69.1%) and that of patients without distant disease was 80.3% (95% CI: 73.5%-87.8%). The survival outcomes varied by tumor size, histology, disease stage, patient age at diagnosis, and the presence of extrathyroidal extension (P < .05). ConclusionsThe use of adjuvant EBRT for nonanaplastic thyroid cancer remained stable and low in California from 2003 to 2017. The comparative efficacy of EBRT was not discernible in this study, but disease control appeared durable in select patients. Well-controlled observational studies and/or prospective studies are needed to better define which patients benefit from EBRT.

Application of EM Algorithm to Mixture Cure Model for Grouped Relative Survival Data

The interest in estimating the probability of cure has been increas ing in cancer survival analysis as the cure of some cancer sites is becoming a reality. Mixture cure models have been used to model the failure time data with the existence of long-term survivors. The mixture cure model assumes that a fraction of the survivors are cured from the disease of interest. The failure time distribution for the uncured individuals (latency) can be mod eled by either parametric models or a semi-parametric proportional hazards model. In the model, the probability of cure and the latency distribution are both related to the prognostic factors and patients’ characteristics. The maximum likelihood estimates (MLEs) of these parameters can be obtained using the Newton-Raphson algorithm. The EM algorithm has been proposed as a simple alternative by Larson and Dinse (1985) and Taylor (1995). in various setting for the cause-specific survival analysis. This approach is ex tended here to the grouped relative survival data. The methods are applied to analyze the colorectal cancer relative survival data from the Surveillance, Epidemiology, and End Results (SEER) program.

The Impact of Age on the Outcome of Primary Treatment for Classical Hodgkin's Lymphoma: 70 Years of Age Is a Clinical Relevant Cutpoint and the Most Important Predictor of Overall Survival

Introduction: Classical Hodgkin lymphoma (cHL) typically affects younger patients but 15-35% are &amp;gt;60 years. The age used to define an elderly population has varied but age 60 is frequently used. A clinically relevant definition of older age could be based on the use of alternate treatments due to different efficacy and/or toxicity. Treatment outcomes may also be influenced by tumor biology and patient comorbidity that vary with age. We evaluated the effect of age on treatment outcomes in cHL. Methods: All cHL patients treated at our centre between Jan 1999 and Dec 2015 were retrospectively analyzed. Clinical data were obtained from prospectively collected Lymphoma database and additional data was manually retrieved. Treatment for localized disease was combined modality (2-4 cycles of ABVD and potentially 6 cycles for bulk disease &amp;gt; 10 cm; radiation doses 20-35 Gy) with advanced disease typically receiving chemotherapy alone (ABVD 6-8 cycles). Older patients received individualized treatment. We used the Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI), (Sorror Blood 2005) as the elements can be abstracted retrospectively. Results: 607 patients were identified; 14% were &amp;gt;60 years and 6% were age &amp;gt;70. Baseline characteristics are outlined in table 1. Patients &amp;gt;70 presented more frequently with high-risk HCT-CI and worse ECOG PS. Patients &amp;gt; 60 presented more frequently with advanced stage (61-70 age group: 40%; &amp;gt;70 years: 46%). 65% of the patients age &amp;gt;70 presented with an IPS of &amp;gt;3. Chemotherapy alone approaches were used more commonly in older patients (age 61-70: 40%; age 70+: 51%) than in those &amp;lt;60 years (25%). Within the whole cohort 12 patients received non-anthracycline based treatment (&amp;lt;60: n=4; 61-70: n=1; and &amp;gt;70: n=7).For patients &amp;lt;60 and &amp;gt;70 this decision was made due to prior comorbidities that precluded the use of standard treatment, and for the patient in the 61-70 was because of acute toxicity with ABVD-based chemotherapy. Treatment was discontinued in 33% of the patients &amp;gt; 70 (77% due to toxicity), 21% in the 61-70 years group (30% toxicity) and 6% in patients &amp;lt;60 (29% toxicity). Patients &amp;gt; 70 had higher rates of grade 3-5 febrile neutropenia (28% versus 15% [age 61-70] and 7% [age &amp;lt;60]). Bleomycin toxicity was more common in older patients (age &amp;gt;70: grade 3-4 events 12% of the patients with discontinuation in 66%; age 61-70: 13% with discontinuation rate of 20%) compared to a 1% rate of grade 3-5 events in age &amp;lt;60. There was a grade 5 episode of febrile neutropenia in &amp;gt;70 group and 1 death related to bleomycin in age &amp;lt;60. With a median follow up of 8.6 years, the 10-year OS and PFS were 80.5% and 71.2%, respectively. By age-group, the 10-year OS was 88% (&amp;lt;60 years), 57% (61-70 years) and 15% (age &amp;gt;70 years); (p&amp;lt;0.001) (Figure 1a-b). In multivariable analysis for OS, age 61-70 (HR 2.44, p=0.002) and age &amp;gt;70 (HR 5.72, p=0.001), non-anthracycline based chemotherapy (HR 3.69, p&amp;lt;0.001), high-risk HCT-CI (HR 3.03, p=0.001) and ECOG 2-4 (HR 1.8, p=0.017), were significant. Age &amp;gt;70, type of chemotherapy, high-risk HCT-CI, and advanced stage were significant for PFS in the multivariable analysis (Table 2a-b). Death due to disease or toxicity at 10 years was 13.6% (age &amp;lt;60: 9.7%, 61-70 years: 23.2%; and for age &amp;gt; 70: 50.7%; [p=&amp;lt;0.001]) (Figure 2a-b). Multivariable analysis for cause-specific survival identified age &amp;gt;70 years (HR 4.04, p=&amp;lt;0.001), extranodal disease (HR 2.57, p=0.001) and ECOG 2-4 (HR 2.10, p=0.010) as significant predictors(Table 3). Conclusions: Age &amp;gt;70 years is a clinically relevant age cutoff as it has additional prognostic significance and greater rates of treatment discontinuation and toxicity compared to age 60. The HCT-CI is a useful predictor of outcome in cHL and should be validated prospectively. In multivariable analysis, age, type of treatment, comorbidity and ECOG performance status are independent predictors of OS. Further studies are ongoing to validate these findings and assess biologic differences in older versus younger cHL patients. Disclosures Tsang: Nordic Nanovector: Research Funding. Kridel:Gilead Sciences: Research Funding. Kukreti:Celgene: Honoraria; Amgen: Honoraria; Takeda: Honoraria. Prica:Celgene: Honoraria; Janssen: Honoraria. Kuruvilla:Janssen: Research Funding; Roche: Honoraria; Novartis: Honoraria; Merck: Honoraria; Gilead: Honoraria; Seattle Genetics: Consultancy; Roche: Consultancy; Merck: Consultancy; Karyopharm: Consultancy; Celgene: Honoraria; BMS: Honoraria; BMS: Consultancy; Abbvie: Consultancy; Gilead: Consultancy; Astra Zeneca: Honoraria; Janssen: Honoraria; Roche: Research Funding; Amgen: Honoraria; Seattle Genetics: Honoraria; Karyopharm: Honoraria.

Abstract 664: Surgery plus adjuvant radiation as a valid treatment option for primary central nervous system lymphoma (PCSNL)

Abstract Background: Recent studies of primary central nervous system lymphoma (PCNSL) have found an association between cytoreductive surgery and survival, challenging the traditional notion that surgery is not beneficial and potentially harmful. However, no studies have examined outcomes after surgery plus adjuvant treatment. We investigated treatment-related outcomes for surgery plus radiation using data from the Surveillance, Epidemiology, and End Results (SEER) Program. Methods: The SEER database was queried to collect cases of histologically confirmed non-Hodgkin's lymphoma within the CNS diagnosed between 1995-2014. Median survival times were determined by the Kaplan-Meier method and compared using the log-rank test. Predictors of overall survival and cause-specific survival were determined using the Cox proportional hazards regression model. Treatment modalities were categorized as biopsy alone, biopsy plus radiation therapy (RT), surgery alone, and surgery + RT. Biopsy alone was used as the reference category. Subgroup analysis stratified patients by extent of surgical resection and recursive partition analysis (RPA) risk group. Results: We identified 5,417 cases that met search criteria, 39% of which received surgical resection. Median survival times for biopsy alone (n=1,824, 34%), biopsy + RT (n=1,460, 27%), surgery alone (n=1,222, 23%), and surgery + RT (n=911, 17%) were 7, 8, 20, and 27 months, respectively (p&amp;lt;0.0001). On multivariable analysis, RT after surgery was associated with a 13% incremental increase in overall survival (Hazard Ratio [HR]=0.71, p&amp;lt;0.0001 vs. HR=0.58, p&amp;lt;0.0001). When analyzing by extent of resection, median survival times for subtotal resection alone (n=111, 2%), gross-total resection alone (n=583, 11%), subtotal resection + RT (n=98, 2%), and gross-total resection + RT (n=459, 8.5%) were 10, 20, 20, and 27 months, respectively (p&amp;lt;0.0001). RT after surgery was independently associated with increased survival in the gross-total resection subgroup (HR=0.85, p=0.046) and in all patients who received surgery (HR=0.87, p=0.017). RT after surgery was also associated with an incremental increase in survival in the RPA class I (HR=0.47, p&amp;lt;0.0001 vs. 0.40, p&amp;lt;0.0001) and class II-III (HR=0.77, p&amp;lt;0.0001 vs. HR=0.66, p&amp;lt;0.0001) subgroups. All findings were confirmed by multivariable analysis of cause-specific survival. Conclusion: Surgical resection of PCNSL in the general population is more common than previously thought. Radiation therapy after surgery is associated with increased survival, regardless of the extent of surgical resection or the patient's RPA risk category. Neurotoxicity, dosing, and effects of concurrent chemotherapy should be addressed in future studies. Citation Format: Connor J. Kinslow, Ali I. Rae, Alfred I. Neugut, Christopher M. Adams, Sameer A. Sheth, Guy M. McKhann, Michael B. Sisti, Jeffrey N. Bruce, Fabio M. Iwamoto, Adam M. Sonabend, Tony J. Wang. Surgery plus adjuvant radiation as a valid treatment option for primary central nervous system lymphoma (PCSNL) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 664.

High-dose 3D-CRT in the radical and postoperative setting for prostate cancer. Analysis of survival and late rectal and urinary toxicity.

The aim of the study was to retrospectively compare outcome and complications of prostate cancer patients treated with a curative and postoperative intent using a pretreatment defined NCCN classification. A total of 103 patients was treated curatively (RAD) and 94 postoperatively (POST-OP). The mean age was higher in the RAD group (72.6 years; range, 56.4-85.1) than in the POST-OP group (65.4 years; range, 43.9-77) (P <0.0001). According to the NCCN prognostic classification, 13 (12%) patients were at low risk, 48 (47%) at intermediate risk and 42 (41%) at high risk in the RAD group. In the POST-OP group, 13 (14%) patients were low risk, 37 (40%) at intermediate risk and 44 (46%) at high risk. Hormone therapy was used in 98 patients (95%) in the RAD group and 45 patients (47.8%) in the POST-OP group. Patients were treated with three-dimensional conformal radiotherapy. The prescription dose was 80 Gy in 2-Gy fractions in the RAD group and 70 Gy in 2-Gy fractions in the POST-OP. No biochemical, clinical relapse was found in low-risk patients in the RAD group and 1 relapse was found in the POST-OP group. The largest number of relapses occurred (39%) and (33%) in intermediate-high risk in RAD and POST-OP groups, respectively. In the cause-specific survival analysis, no significant differences were found in the high-risk group between RAD and POST-OP groups (P = 0.9). In the analysis of 5-year biochemical relapse-free survival, no significant differences were found in the high-risk group between RAD and POST-OP groups (P = 0.1020). Radiotherapy in the RAD low-risk group was an excellent treatment. RAD and POST-OP radiotherapy were well tolerated with very low toxicity. The cause-specific survival at 5 years was 95% and 97% for the two treatment groups, RAD and POST-OP, respectively (logrank test, P = 0.2908).

TERT promoter mutations in clear cell renal cell carcinoma.

We screened promoter region of the telomerase reverse transcriptase (TERT) for activating somatic mutations in 188 tumors from patients with clear cell renal cell carcinoma (ccRCC). Twelve tumors (6.4%) carried a mutation within the core promoter region of the gene. The mutations were less frequent in high grade tumors compared to low grade tumors [odds ratio (OR) = 0.15, 95% confidence interval (CI) = 0.03-0.72, p = 0.02]. Multivariate analysis for cause specific survival showed statistically significant poor outcome in patients with TERT promoter mutations [hazard ratio (HR) = 2.90, 95% CI = 1.13-7.39, p = 0.03]. A common polymorphism (rs2853669) within the locus seemed to act as a modifier of the effect of the mutations on patient survival as the noncarriers of the variant allele with the TERT promoter mutations showed worst survival (HR = 3.34, 95% CI = 1.24-8.98, p = 0.02). We also measured relative telomere length (RTL) in tumors and difference between tumors with and without the TERT promoter mutations was not statistically significant. Similarly, no difference in patient survival based on RTL in tumors was observed. Our study showed a relatively low frequency of TERT promoter mutations in ccRCC. Nevertheless, patients with the mutations, particularly in the absence of the rs2853669 variant showed the worst disease-specific survival. Thus, it is possible that the TERT promoter mutations define a small subset of tumors with an aggressive behavior.

Abstract C32: PTEN and p53 expression in endometrial cancer correlated with clinicopathological phenotype.

Abstract p53 overexpression and loss of PTEN expression have been implicated in the pathogenesis of endometrial cancer. Our aim was to correlate expression levels of these proteins with clinicopathological parameters to characterise their utility as biomarkers. Immunohistochemistry was done on 49 cases of formalin fixed paraffin embedded endometrial cancer tissue for p53 and 47 for PTEN expression. For p53 staining the Hue Saturation and Intensity mathematical model was used to evaluate different degrees of positivity of the immunohistochemical stain. The quick score was used for p53 and immunoreactive score for PTEN was done to score immunoreactivity. For PTEN, average percentage of positive cells and intensity was evaluated and the immunoreactive score was calculated. Both these scoring methods incorporated percentage of positive cells and staining intensity. Univariate Cox regression analysis for cause specific survival showed a hazard ratio of 9.2 for p53 overexpression (P&amp;lt;0.05). High levels of P53 were significantly associated with histologic type, grade, LVI and recurrent disease. There was no significant association between PTEN expression and clinicopathological features but it was noted that the 8 patients who relapsed were PTEN negative. Cause specific survival could not be assessed for PTEN expression due to the lack of events in this group. PTEN and p53 (n=46) combined analysis failed to demonstrate a significant association on prognostic features in this group. Overexpression of P53 has a negative effect on disease specific survival and was associated with poor prognostic features. We did not demonstrate a significant association with clinicopathological features assessed and PTEN expression. However of the 8 patients who relapsed all were PTEN negative and 7 were p53 positive. Dual assessment of p53 and PTEN warrants further investigation as a prognostic indicator. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):C32. Citation Format: Bihani Kularatne, Arrigo Capitanio, Rupali Arora, Philippa Jones, Andre Lopes, Jennifer Paterson, Rebecca Kristeleit. PTEN and p53 expression in endometrial cancer correlated with clinicopathological phenotype. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr C32.

Diffuse large B-cell lymphoma in adults aged 75 years and older: a single institution analysis of cause-specific survival and prognostic factors

Very elderly patients (75 years and older) with diffuse large B-cell lymphoma (DLBCL) will be increasingly considered for cancer treatment as the population ages, but are underrepresented in clinical trials. Here we report outcomes of very elderly DLBCL patients treated in the modern era at the Oregon Health and Science University (OHSU). We queried the OHSU Tumor Registry for DLBCL cases treated since 2002. A total of 73 patients aged 75 years or older were analyzed under Institutional Review Board approval. With a median follow up of 31 months, cause-specific survival was 58% and overall survival 51% at 3 years. Incorporation of an anthracycline did not influence outcomes. More than one extranodal site or poor-risk disease by Revised International Prognostic Index score were adversely prognostic, but pathologic features studied were not. Very elderly patients with DLBCL require prospective studies, which employ novel risk stratification and therapeutic approaches.

Phosphorylated EGFR at tyrosine 1173 correlates with poor prognosis in oral squamous cell carcinomas

To evaluate the expression of epidermal growth factor receptor (EGFR) and phosphorylated EGFR (pEGFR), in oral squamous cell carcinomas (OSCC). We examined their utility as prognostic markers by relating to clinicopathological characteristics and the clinical outcome. We analysed 74 primary OSCC and examined immunohistochemical expression of EGFR and pEGFR (phosphorylated at tyrosine 1173) using tissue microarray technology. Their role in survival was assessed by Kaplan-Meier method and Cox regression models. Epidermal growth factor receptor expression was observed in all cases, and pEGFR expression was observed in 41.1% of the cases. We found a significant correlation between EGFR and pEGFR expression (P=0.003). In the multivariable analysis for cause-specific survival, we found an independent prognostic value for pEGFR expression (HR 7.94, 95% CI 2.03-31.06, P=0.003) and for clinical stage (HR 2.88, 95% CI 1.10-7.53, P=0.031). For recurrence-free survival, clinical stage (HR 6.59, 95% CI 1.36-31.90, P=0.019) and tumour grade (HR 3.35, 95% CI 1.07-10.44, P=0.037) presented independent prognostic value. Epidermal growth factor receptor is highly expressed in OSCC and is phosphorylated in more than one-third of the cases. The independent value of pEGFR expression in cause-specific survival of OSCC suggests that this marker may serve as reliable biological marker to identify high-risk subgroups and to guide therapy.

SURVIVAL TRENDS IN CHILDHOOD HEMATOLOGICAL MALIGNANCIES

Survival of patients with childhood hematological malignancies has increased markedly in the past decades. To examine the fine-scale details of how this progress has occurred, we carried out Kaplan–Meier cause-specific survival analysis using the Surveillance Epidemiology and End Results (SEER) dataset for patients with childhood hematological malignancies — Hodgkin's Lymphoma, Non-Hodgkin's Lymphoma, Lymphoblastic Leukemia and Myeloid Leukemia — diagnosed in five eras: 1983–1987; 1988–1992; 1993–1997; 1998–2002 and 2003–2007. We generated Kaplan–Meier estimates of survival for each of the first 24 years after diagnosis. These figures agree with previously reported five- and ten-year values and attest to the remarkable increase in survival that has occurred over the past three decades of medical progress. The trend towards progressively increasing survival shows no sign of slowing, suggesting that we may expect further increases in survival in the years ahead. Most of the increase in survival for childhood hematological malignancies has occurred by reducing the risk of death in the first two years after diagnosis. This may be largely explained by the fact that this is the time period when patients are at highest risk of death.

High-Dose 3D-CRT in the Radical and Postoperative Setting for Prostate Cancer. Analysis of Survival and Late Rectal and Urinary Toxicity

The aim of the study was to retrospectively compare outcome and complications of prostate cancer patients treated with a curative and postoperative intent using a pretreatment defined NCCN classification. A total of 103 patients was treated curatively (RAD) and 94 postoperatively (POST-OP). The mean age was higher in the RAD group (72.6 years; range, 56.4-85.1) than in the POST-OP group (65.4 years; range, 43.9-77) (P <0.0001). According to the NCCN prognostic classification, 13 (12%) patients were at low risk, 48 (47%) at intermediate risk and 42 (41%) at high risk in the RAD group. In the POST-OP group, 13 (14%) patients were low risk, 37 (40%) at intermediate risk and 44 (46%) at high risk. Hormone therapy was used in 98 patients (95%) in the RAD group and 45 patients (47.8%) in the POST-OP group. Patients were treated with three-dimensional conformal radiotherapy. The prescription dose was 80 Gy in 2-Gy fractions in the RAD group and 70 Gy in 2-Gy fractions in the POST-OP. No biochemical, clinical relapse was found in low-risk patients in the RAD group and 1 relapse was found in the POST-OP group. The largest number of relapses occurred (39%) and (33%) in intermediate-high risk in RAD and POST-OP groups, respectively. In the cause-specific survival analysis, no significant differences were found in the high-risk group between RAD and POST-OP groups (P = 0.9). In the analysis of 5-year biochemical relapse-free survival, no significant differences were found in the high-risk group between RAD and POST-OP groups (P = 0.1020). Radiotherapy in the RAD low-risk group was an excellent treatment. RAD and POST-OP radiotherapy were well tolerated with very low toxicity. The cause-specific survival at 5 years was 95% and 97% for the two treatment groups, RAD and POST-OP, respectively (logrank test, P = 0.2908).

Estimation with Cox models: cause-specific survival analysis with misclassified cause of failure.

While epidemiologic and clinical research often aims to analyze predictors of specific endpoints, time-to-the-specific-event analysis can be hampered by problems with cause ascertainment. Under typical assumptions of competing risks analysis (and missing-data settings), we correct the cause-specific proportional hazards analysis when information on the reliability of diagnosis is available. Our method avoids bias in effect estimates at low cost in variance, thus offering a perspective for better-informed decision making. The ratio of different cause-specific hazards can be estimated flexibly for this purpose. It thus complements an all-cause analysis. In a sensitivity analysis, this approach can reveal the likely extent and direction of the bias of a standard cause-specific analysis when the diagnosis is suspect. These 2 uses are illustrated in a randomized vaccine trial and an epidemiologic cohort study, respectively.

Expression of claudins 1, 4, 5, and 7 and occludin, and relationship with prognosis in squamous cell carcinoma of the tongue

Claudins and occludin are tight junctional proteins known to play a role in normal tissues and epithelial tumors. We analyzed the distribution patterns of claudins 1, 4, 5, and 7 and occludin in the superficial and invasive front of squamous cell carcinoma of the tongue of 97 patients and their relationship to cause-specific (squamous cell carcinoma of the tongue) patient survival (median follow-up period of 33.5 months; range, 1-234 months). Claudins 1 and 7 were strongly expressed, claudin 4 had moderate expression, whereas claudin 5 was least expressed. Occludin staining was mostly negative or very weak. Western blot analysis of tongue carcinoma (HSC-3) cells showed that all these proteins are also expressed in vitro. In cause-specific survival analysis, strong and low immunoreactivity of claudin 7 tended to be associated with decreased survival compared with medium immunoreactivity. We suggest that analyzing the immunohistologic staining levels of claudin 7 could be used for the prognostic purposes in patients with tongue squamous cell carcinoma.

Lack of benefit of pelvic radiation in prostate cancer patients with a high risk of positive pelvic lymph nodes treated with high-dose radiation

The use of pelvic radiation for patients with a high risk of lymph node (LN) metastasis (>15%) remains controversial. We reviewed the data at three institutions treating patients with a combination of external-beam radiation therapy and high-dose-rate brachytherapy to address the prognostic implications of the use of the Roach formula and the benefit of pelvic treatment. From 1986 to 2003, 1,491 patients were treated with external-beam radiation therapy and high-dose-rate brachytherapy. The Roach formula [2/3 prostate-specific antigen + (Gleason score -6) x 10] could be calculated for 1,357 patients. Group I consisted of patients having a risk of positive LN < or = 15% (n = 761), Group II had a risk >15% and < or = 30% (n = 422), and Group III had a risk of LN disease >30% (n = 174). A >15% risk of having positive LN was found in 596 patients and was used to determine the benefit of pelvic radiation. The pelvis was treated at two of the cancer centers (n = 312), whereas at the third center (n = 284) radiation therapy was delivered to the prostate and seminal vesicles alone. Average biologic effective dose was > or = 100 Gy (alphabeta = 1.2). Biochemical failure was as per the American Society for Therapeutic Radiology and Oncology definition. Statistics included the log-rank test as well as Cox univariate and multivariate analysis. For all 596 patients with a positive LN risk >15%, median follow-up was 4.3 years, with a mean of 4.8 years. For all cases, median follow-up was 4 years and mean follow-up was 4.4 years. Five-year results for the three groups based on their risk of positive LN were significantly different in terms of biochemical failure (p < 0.001), clinical control (p < 0.001), disease-free survival excluding biochemical failure (p < 0.001), cause-specific survival (p < 0.001), and overall survival (p < 0.001). For all patients with a risk of positive LN >15% (n = 596), Group II (>15-30% risk), or Group III (>30% risk), no benefit was seen in the 5-year rates of clinical failure, cause-specific survival, or overall survival with pelvic radiation. In the Cox multivariate analysis for cause-specific survival, Gleason score (p = 0.009, hazard ratio [HR] 3.1), T stage (p = 0.03, HR 1.8), and year of treatment (p = 0.05, HR 1.1) were significant. A log-rank test for cause-specific survival for all patients (n = 577) by the use of pelvic radiation was not significant (p = 0.99) accounting for high-dose-rate brachytherapy dose, neoadjuvant hormones, Gleason score, prostate-specific antigen, T stage, and year of treatment as covariates. The use of the Roach formula to stratify patients for clinical and biochemical outcomes is excellent. Pelvic radiation added to high prostate radiation doses did not show a clinical benefit for patients at a high risk of pelvic LN disease (>15%) selected using the Roach formula.

Radiotherapy alone or combined with surgery for salivary gland carcinoma

The authors analyzed the outcomes of patients treated with radiotherapy (RT) alone or combined with surgery for carcinoma of the salivary glands. Between October 1964 and June 2003, 224 previously untreated patients were treated with curative intent with RT alone (n = 64) or combined with surgery (n = 160) at the University of Florida College of Medicine (Gainesville, FL). The median follow-up period was 5.0 years (range, 0.4-31.6 years). The 10-year local control rate was 75%. Multivariate analysis of local control revealed that T classification (P < 0.0001) and treatment group (P < 0.0001) impacted this end point. Patients treated with surgery and adjuvant RT had improved local control compared with patients treated with RT alone. The 10-year locoregional control rate was 68%. Multivariate analysis of locoregional control revealed that overall stage (P < 0.0001) and treatment group (P = 0.0002) significantly influenced this end point. The 10-year distant metastasis-free survival rate was 68%. Multivariate analysis of distant metastasis-free survival revealed that overall stage (P < 0.0001) significantly influenced this end point. The 10-year cause-specific and overall survival rates were 57% and 44%, respectively. Multivariate analysis of cause-specific survival revealed that overall stage (P < 0.0001) significantly impacted this end point. Twenty-three patients (10%) experienced severe complications. A substantial proportion of patients with salivary gland carcinoma were cured with surgery combined with adjuvant RT. RT alone was used for patients with unresectable tumors and cured approximately 20% of those with advanced-stage disease. The probability of cure was influenced by the extent of disease and treatment group.