Clinicopathological features, prognostic factor analysis, and survival nomogram of patients with double primary cancers involving lung cancer.

BACKGROUND: Although the incidence of double primary cancers (DPCs) involving lung cancer is rising, they have not been studied sufficiently. This study retrospectively analyzed the clinicopathological and prognostic characteristics of DPC patients with lung cancer and developed a survival nomogram to predict the individual OS rates. METHODS: We included 103 DPC patients with lung cancer from Shengjing Hospital between 2016 and 2021. Based on the 6-month cancer occurrence interval, the cases were categorized as synchronous DPCs (sDPCs) or metachronous DPCs (mDPCs). Furthermore, the mDPCs were subdivided based on whether the lung cancer occurred first (LCF cohort) or the other cancer occurred first (OCF cohort). RESULTS: Among the patients, 35 (33.98%) and 68 (66.02%) had sDPCs and mDPCs, respectively. In the mDPCs cohort, 18 (26.47%) belonged to the LCF cohort and 50 (73.53%) to the OCF cohort. The most frequent primary cancer sites were the breast (27.18%), colorectum (22.33%), and urinary system (18.45%). Independent risk factors for progression-free survival were Stage IV lung cancer (p = 0.008) and failure to undergo radical lung cancer surgery (p = 0.028). The risk factors for OS included squamous carcinoma (p = 0.048), Stage IV lung cancer (p = 0.001), single cancer resection plus drug therapy (p < 0.001), drug therapy alone (p = 0.002), failure to undergo radical lung cancer surgery (p = 0.014), and chemotherapy (p = 0.042). The median OS was 37 months, with 3- and 5-year rates of 50.9% and 35.9%, respectively. CONCLUSION: DPCs involving lung cancer account for 1.11% of cases. The breast, colorectum, and urinary system were the most common extra-pulmonary sites, and mDPCs were more frequent than sDPCs. Radical lung cancer surgery significantly affects prognosis, and drug therapy alone may be preferable when only one tumor is operable. The developed nomogram can accurately predict individual 3-year and 5-year OS rates.

High incidence of lung cancer death after curative endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma.

BACKGROUND AND AIM: Following treatment of superficial esophageal squamous cell carcinoma (ESCC), surveillance for a second primary malignancy (SPM) is necessary. However, detailed evidence regarding the timing and prognosis of SPMs is insufficient. We aimed to clarify the details of SPMs and their effects on patient outcomes. METHODS: This retrospective, multicenter study involved 11 hospitals. Patients with superficial ESCC curatively resected using endoscopic submucosal dissection between May 2005 and December 2012, were included in this study. RESULTS: The 5-year survival rate of 187 patients was 92.6% during a median follow-up duration of 96.8 months. Thirty-one patients died, 14 of whom died of SPMs. Compared to patients with SPMs detectable by esophagogastroduodenoscopy (EGD), patients with SPMs detectable only by modalities other than EGD had a significantly higher mortality rate (p < 0.001). Patients with second primary lung cancer (LC) had a high mortality rate (56.3%). Univariate and multivariate analyses showed that multiple Lugol-voiding lesions (LVLs) tended to be associated with SPMs (p = 0.077, hazard ratio [HR] 4.43, 95% confidence interval [CI]: 0.91-6.50), and metachronous ESCC was an independent risk factor for the incidence of second primary LC (p = 0.037, HR 3.51, 95% CI: 1.08-11.41). CONCLUSIONS: SPMs that cannot be detected by EGD, such as LC, must be considered after the curative resection of ESCC. We suggest strict screening by both EGD and computed tomography for patients with multiple LVLs or metachronous ESCC to detect SPMs in their early stages.

Enhanced Survival with Lymphadenectomy in Early-Stage Metachronous Second Primary Lung Cancer: A Retrospective Analysis.

INTRODUCTION: Lymphadenectomy is a cornerstone in the surgical management of resectable primary lung cancer. However, its prognostic significance in early-stage metachronous second primary lung cancer (MSPLC) remains poorly understood. This retrospective study aimed to evaluate the prognostic impact of lymphadenectomy in these patients using data from the Surveillance, Epidemiology, and End Results (SEER) Database. METHODS: A retrospective cohort study was conducted using data from the SEER Database for patients surgically treated for stage I MSPLC between 2004 and 2015. Propensity score-matching was employed to create comparable cohorts, and the Cox proportional hazards model was utilized to estimate the hazard ratio (HR) for overall survival after lymphadenectomy compared to non-lymphadenectomy. Survival analysis was performed using Kaplan-Meier curves and the log-rank test. RESULTS: Among 920 identified patients with MSPLC, 574 (62.4%) underwent lymphadenectomy. Propensity score-matching yielded 255 patients in both the lymphadenectomy and non-lymphadenectomy groups. Over a median follow-up of 38 months, the 5-year overall survival probability after a diagnosis of MSPLC was 58.7% in the lymphadenectomy group and 43.9% in the non-lymphadenectomy group (HR: 0.76; 95% confidence interval 0.64-0.90; p = 0.002). CONCLUSION: In this population-based study, lymphadenectomy is associated with prolonged overall survival in patients with stage I MSPLC. These findings suggest the potential benefit of incorporating lymphadenectomy into the surgical management of MSPLC, providing valuable guidance for thoracic surgeons in clinical decision-making.

Impact of risk-based therapy on late morbidity and mortality in neuroblastoma survivors: a report from the Childhood Cancer Survivor Study.

BACKGROUND: Early efforts at risk-adapted therapy for neuroblastoma are predicted to result in differential late effects; the magnitude of these differences has not been well described. METHODS: Late mortality, subsequent malignant neoplasms (SMNs), and severe/life-threatening chronic health conditions (CHCs), graded according to CTCAE v4.03, were assessed among 5-year Childhood Cancer Survivor Study (CCSS) survivors of neuroblastoma diagnosed 1987-1999. Using age, stage at diagnosis, and treatment, survivors were classified into risk groups (low [n = 425]; intermediate [n = 252]; high [n = 245]). Standardized mortality ratios (SMRs) and standardized incidence ratios (SIRs) of SMNs were compared with matched population controls. Cox regression models estimated hazard ratios (HRs) and 95% confidence intervals for CHC compared with 1029 CCSS siblings. RESULTS: Among survivors (49.8% male; median age = 21 years, range = 7-42; median follow-up = 19.3 years, range = 5-29.9), 80% with low-risk disease were treated with surgery alone, whereas 79.1% with high-risk disease received surgery, radiation, chemotherapy ± autologous stem cell transplant (ASCT). All-cause mortality was elevated across risk groups (SMRhigh = 27.7 [21.4-35.8]; SMRintermediate = 3.3 [1.7-6.5]; SMRlow = 2.8 [1.7-4.8]). SMN risk was increased among high- and intermediate-risk survivors (SIRhigh = 28.0 [18.5-42.3]; SIRintermediate = 3.7 [1.2-11.3]) but did not differ from the US population for survivors of low-risk disease. Compared with siblings, survivors had an increased risk of grade 3-5 CHCs, particularly among those with high-risk disease (HRhigh = 16.1 [11.2-23.2]; HRintermediate = 6.3 [3.8-10.5]; HRlow = 1.8 [1.1-3.1]). CONCLUSION: Survivors of high-risk disease treated in the early days of risk stratification carry a markedly elevated burden of late recurrence, SMN, and organ-related multimorbidity, whereas survivors of low/intermediate-risk disease have a modest risk of late adverse outcomes.

Survival difference between secondary and de novo acute myeloid leukemia by age, antecedent cancer types, and chemotherapy receipt.

BACKGROUND: This study compared the survival of persons with secondary acute myeloid leukemia (sAML) to those with de novo AML (dnAML) by age at AML diagnosis, chemotherapy receipt, and cancer type preceding sAML diagnosis. METHODS: Data from Surveillance, Epidemiology, and End Results 17 Registries were used, which included 47,704 individuals diagnosed with AML between 2001 and 2018. Multivariable Cox proportional hazards regression was used to compare AML-specific survival between sAML and dnAML. Trends in 5-year age-standardized relative survival were examined via the Joinpoint survival model. RESULTS: Overall, individuals with sAML had an 8% higher risk of dying from AML (hazard ratio [HR], 1.08; 95% confidence interval [CI], 1.05-1.11) compared to those with dnAML. Disparities widened with younger age at diagnosis, particularly in those who received chemotherapy for AML (HR, 1.14; 95% CI, 1.10-1.19). In persons aged 20-64 years and who received chemotherapy, HRs were greatest for those with antecedent myelodysplastic syndrome (HR, 2.04; 95% CI, 1.83-2.28), ovarian cancer (HR, 1.91; 95% CI, 1.19-3.08), head and neck cancer (HR, 1.55; 95% CI, 1.02-2.36), leukemia (HR, 1.45; 95% CI, 1.12-1.89), and non-Hodgkin lymphoma (HR, 1.42; 95% CI, 1.20-1.69). Among those aged ≥65 years and who received chemotherapy, HRs were highest for those with antecedent cervical cancer (HR, 2.42; 95% CI, 1.15-5.10) and myelodysplastic syndrome (HR, 1.28; 95% CI, 1.19-1.38). The 5-year relative survival improved 0.3% per year for sAML slower than 0.86% per year for dnAML. Consequently, the survival gap widened from 7.2% (95% CI, 5.4%-9.0%) during the period 2001-2003 to 14.3% (95% CI, 12.8%-15.8%) during the period 2012-2014. CONCLUSIONS: Significant survival disparities exist between sAML and dnAML on the basis of age at diagnosis, chemotherapy receipt, and antecedent cancer, which highlights opportunities to improve outcomes among those diagnosed with sAML.

Thyrotropin suppression therapy using levothyroxine does not negatively affect breast cancer prognosis.

INTRODUCTION: Breast cancer (BC) and thyroid dysfunction are common in females, yet the relationship between thyroid hormone and BC is unclear. To search for the connection between thyrotropin and BC, we contradistinguished BC patients with or without synchronous second primary thyroid cancer (TC) with surgery using data from the Surveillance, Epidemiology, and End Results (SEER) database. Theoretically, according to the ATA (American Thyroid Association) guidelines, all TC patients were treated with thyrotropin suppressive therapy only from 2010 to 2015. MATERIALS AND METHODS: Data from BC patients with a synchronous second TC with surgery (BC2TC) and only BC patients (1BC) during 2010-2015 were extracted from the SEER database. Differences in the clinicopathological characteristics between BC2TC and 1BC patients were analyzed by chi-square tests. Comparisons of the disease-specific survival (DSS) and overall survival (OS) curves between these two groups were performed with the log-rank (Mantel-Cox) test. RESULTS: Within this dataset, we identified 134 BC2TC patients during the period from 2010 to 2015. Significant differences between the BC2TC and 1BC groups were found only for different ages and TNM (tumor-node-metastasis status) stages. There were no significant differences in DSS between the two cohorts (P = 0.060). The same tendencies in OS or DSS were observed for the different age groups and different TNM groups, even the stage I, N0 (without metastases to lymph nodes), and ER (+) (estrogen receptor (ER)-positive) groups. CONCLUSIONS: There were no remarkable differences in survival between the BC2TC and 1BC groups, and thyrotropin suppression therapy using levothyroxine did not negatively affect BC prognosis.

Secondary primary malignancy in patients with head and neck squamous cell carcinoma: 27-year experience from the perspective of diagnostic tools.

BACKGROUND: The survival rate of head and neck squamous cell carcinoma (HNSCC) patients with secondary primary malignancy (SPM) showed no significant improvement for decades, however, the impact of advances in diagnostic tools is rarely mentioned. This study investigated the clinical characteristic of HNSCC with SPM over a 27-year period especially from the perspective of diagnostic tools. METHODS: This study evaluated 157 HNSCC patients with SPM. The patients were divided into two groups according to the time of SPM diagnosis (Group A:1992-2003; Group B: 2004-2014). Age, gender, stage of first primary malignancy (FPM), SPM interval, overall survival, and disease-free survival were compared between groups. RESULTS: Group B had significantly more SPM developed rate (p = 0.002), more SPM patients with advanced stage of FPM (p = 0.001), synchronous SPM (p = 0.006), and shorter SPM interval (p<0.001) compared to Group A. The survival rate in Group B was not significantly better than Group A. CONCLUSION: Among patients diagnosed with HNSCC recently, more SPMs are diagnosed in a shorter time interval and in a more advanced stage. The overall advances in diagnostic tools cannot significantly improve SPM survival, however, it enables more patients to receive corresponding treatment.

Incidence and relative risk of metachronous second primary cancers for 16 cancer sites, Osaka, Japan, 2000-2015: Population-based analysis.

BACKGROUND: An increasing number of cancer survivors have developed multiple primaries. This study aims to describe the incidence and risk patterns of metachronous second primary cancers (SPCs) in Osaka, Japan. METHODS: Data were obtained from the Osaka Cancer Registry, a population-based database of all cancers diagnosed in Osaka. The study subjects were individuals who were first diagnosed with invasive cancers in 16 major cancer sites during 2000-2014, aged 15-79 years, survived at least 3 months, and were followed up for 10 years. We measured incidence rates, cumulative risks, and standardized incidence ratios (SIRs: with the Osaka general population as the referent) of developing SPCs during 3 months to 10 years after the first diagnosis. RESULTS: During 2000-2015, among 418,791 cancer survivors, 24,368 (5.8%) developed SPCs within 10 years of first diagnosis. Males had higher incidence rates than females except among young-onset survivors (aged 15-39 years). 10-year cumulative risks among survivors aged 70-79 years (the most dominant age group) were 24.0% (male) and 11.8% (female). 10-year SIRs were 1.38 (95% CI, 1.36-1.40; male) and 1.44 (95% CI, 1.41-1.48; female) with higher estimates among younger survivors in both sexes. Strong bidirectional associations were observed between oral/pharyngeal, esophageal, and laryngeal cancers. Survivors of any smoking-related cancers had elevated SIRs of developing smoking-related SPCs. Similar results were observed for alcohol-related cancers. CONCLUSIONS: Cancer survivors are at excess risk of developing SPCs compared to the general population. Continued surveillance is warranted to inform survivorship care through risk-based long-term care planning and lifestyle-changing efforts to prevent new cancers.

Impact of prior cancer on the overall survival of patients with nasopharyngeal carcinoma.

PURPOSE: Prior cancer history is an important exclusion criterion from clinical trials and may decrease their generalizability. This study aimed to investigate the impact of prior cancer on the prognosis of patients with nasopharyngeal carcinoma and to describe their characteristics. MATERIALS AND METHODS: Data of patients with nasopharyngeal carcinoma diagnosed between 2010 and 2015 were collected from the Surveillance, Epidemiology, and End Results database. The discrepancy in baseline characteristics was adjusted by propensity score matching. Kaplan-Meier and Cox regression analyses were performed to assess the impact of prior cancer on overall survival. RESULTS: A total of 3412 individuals were identified, of which 418 (12.25%) had prior cancer. Prostate cancer was the most frequently detected type of prior cancer (18.42%). Nearly 45% of the prior cancers were diagnosed within 5 years before the nasopharyngeal carcinoma. Patients with prior cancer had an inferior survival compared to those without prior cancer (p < 0.001). Notably, patients with prior prostate, breast, hematological, and nasopharyngeal cancers had a non-inferior overall survival. Prior cancer history was an independent factor of poor overall survival (hazard ratio = 1.329, p = 0.003). CONCLUSIONS: This is the first study to provide the comprehensive insight that patients with nasopharyngeal carcinoma and prior cancer have lower overall survival. Different prior cancer types had a different impact on the clinical outcome, suggesting that the exclusion criteria should be individually defined by unique cancer types.

Survival outcomes following radical cystectomy in patients with prior pelvic radiation for prostate cancer: A matched cohort analysis.

OBJECTIVES: To determine the impact of prior pelvic radiation therapy (XRT) on outcomes following radical cystectomy (RC) for bladder cancer. MATERIALS AND METHODS: We performed a retrospective review comparing patients with bladder cancer requiring RC and prior history of XRT for prostate cancer to those undergoing RC without XRT history at our institution from 2011-2018. Propensity score matching was performed with the following variables: age, chronic kidney disease, nutritional deficiency, neoadjuvant chemotherapy use, Charlson comorbidity index, surgical approach, urinary diversion type, and pathologic T-stage. Perioperative, pathologic and oncologic outcomes were analyzed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Categorical variables were assessed utilizing the Pearson Chi Square Test, and continuous variables with the Wilcoxon rank-sum test. The Kaplan-Meier method with stratified-log rank was used to compare survival outcomes. Multivariable Cox proportional hazards models were utilized to identify predictors of overall and recurrence free survival. RESULTS: 227 patients were included, of which 47 had radiotherapy for prostate cancer. 47% of patients in the radiation cohort received external beam radiation therapy, 47% received brachytherapy and 7% received both. There were no differences in recurrence-free survival (P = 0.82) or overall survival (P = 0.25). Statistically significant differences in perioperative or postoperative outcomes such as 90-day complication, readmission, mortality rates, or ureteroenteric anastomotic stricture rates were not found. Rates of node-positive disease, median lymph node yield, positive surgical margin rates, lymphovascular invasion, or variant histology were not significantly different between cohorts. CONCLUSIONS: After matching for T-stage and other clinical variables, history of pelvic XRT for prostate cancer in patients who later required RC for bladder cancer, was not associated with an increased rate of perioperative complications or an independent predictor of RFS or OS.

Pathological and genomic phenotype of second neuroendocrine carcinoma during long-term follow-up after radical radiotherapy for nasopharyngeal carcinoma.

BACKGROUND: Second head and neck neuroendocrine carcinoma (NEC) after radical radiotherapy for nasopharyngeal carcinoma (NPC) treatment is rarely reported. The prognosis of second cancer is poor, and our research focuses on finding a breakthrough in the treatment. In this study, we aimed to investigate clinicopathological characteristics and to identify the genomic landscape of second head and neck NECs. METHODS: We collected five second head and neck NEC cases in the recent three years from our patient database. Clinicopathological data and images were obtained. Genomic analysis was performed using high-throughput second generation sequencing. KEGG pathway enrichment analyses between high-frequency mutations were performed using the STRING database. RESULTS: All patients had been diagnosed with second NEC, according to the pathological observations. The interval between diagnosis of NPC and NEC ranged from 10 to 18 years. Two patients had brain or liver metastasis at three and nine months, respectively, after the diagnosis of NEC. Three patients died of the disease with the overall survival time ranging from three to nine months. Commonly altered genes (50%) in second head and neck NECs included TP53, RB1, NOTCH2, PTEN, POLG, KMT2C, U2AF1, EPPK1, ELAC2, DAXX, COL22A1, and ABL1. Those genetic lesions might affect p53 signaling, MAPK signaling, PI3K-Akt signaling, sphingolipid signaling, and neurotrophin signaling pathways. CONCLUSIONS: Second head and neck NECs had poor prognosis. We revealed, for the first time, the mutational landscape, high-frequency somatic mutations, and potential signaling pathways of second head and neck NECs. Its optimal treatment model needs to be further studied in future clinical trials.

Types of second primary cancer influence overall survival in cutaneous melanoma.

BACKGROUND: Favorable survival in malignant cutaneous melanoma (melanoma) has increased the likelihood of second primary cancer (SPC). We assess the influence of patient characteristics at diagnosis of first melanoma and the type of SPC (second melanoma and other SPC) on overall survival. METHODS: We used the Swedish Cancer Registry data to assess overall survival in melanoma for the period 1990 to 2015. Kaplan-Meier curves were plotted and hazard ratios (HRs) were estimated with Cox regression models by considering SPC diagnosis as a time-dependent variable. RESULTS: A total of 46,726 patients were diagnosed with melanoma, and 15.3% of them developed SPC, among which, two thirds were other SPCs. Second melanomas were diagnosed early (31% during the first year) compared to non-melanoma SPCs (9.5%). Survival for women with second melanoma or other SPC (56 and 21% alive after 25 years of follow-up, respectively) exceeded the male rates (21 and 10%, respectively) but all these figures were lower than for females (60% alive) or males (48%) without SPC. Time dependent analysis showed vastly increased HRs for cancer types that are fatal also as first cancers, but SPC-specific HRs remained relatively uniform, irrespective of SPC diagnosed soon or late after first melanoma. In early-onset melanoma, SPC diagnosis after 10 years may not negatively influence overall survival. CONCLUSIONS: As the overall survival of patients with many types of SPCs is unfavorable, advice about health lifestyle should benefit smoking patients and early detection methods may be recommended for SPCs of the breast, prostate and colorectum.

Distinct patterns of occurrence, common associations, and survival of patients with second primary maligancies: A 5-year single institute experience with review of literature.

BACKGROUND: Multiple primary malignancy (MPM) is defined as occurrence of two or more synchronous or metachronous primary malignancies. With the rise in cancer burden and meticulous screening of index primary malignancy (IPM) during treatment, increased incidence of second primary malignancy (SPM) is expected. This study was undertaken with an attempt to analyze the incidence, commonest associations, management strategies, and clinical outcomes of MPM. MATERIALS AND METHODS: This is an observational retrospective study carried out in a single institute with patients registered between 1st January 2015 and 31st August 2019. The International Association of Cancer Registries and International Agency for Research on Cancer (IACR/IARC) definition was used for identification of IPM and SPM. Synchronous SPM was defined as malignancy occurring within 6 months from the diagnosis of IPM. RESULTS: Out of 16,461 registered patients during the study interval, 44 (0.26%) cases were found to have MPM. A total of 31 (70.5%) cases were women and 13 (29.5%) cases were men. Median age at presentation of IPM was 48 years and of SPM was 56 years, with median duration between two primaries being 38 months. Seven patients (15.9%) had synchronous malignancies. Gynecological tumors were the most common site of IPM presentation (n = 14, 31.8%) followed by breast (n = 09, 20.5%) and head and neck tumors (n = 07, 15.9%), respectively. The most common SPM was gynecological tumors (n = 12, 27.3%) followed by gastrointestinal malignancies (n = 10, 23.3%). Curative treatment was offered to 88% of patients with IPM and 70% patients with SPM. At a median follow-up of 365 days, 21 (47.72%) patients were disease free, six (13.6%) died of disease and nine (20.5%) were lost to follow-up. CONCLUSION: The study emphasizes the importance of detecting SPM as a result of improved diagnostic and screening procedures. Clinicians should be aware of it and offer multidisciplinary management.

De novo isolated myeloid sarcoma: comparative analysis of survival in 19 consecutive cases.

Institutional database search (1999-2020) for acute myeloid leukaemia (AML) identified 109 cases of myeloid sarcoma (MS), of which 19 were isolated and presented de novo. The latter displayed longer survival (median 78 months), compared to MS with synchronous intramedullary AML (n = 32; median 16 months) and de novo AML without MS (n = 729; median 22 months; P = 0·13). However, the difference in survival was no longer apparent after accounting for bone marrow cytogenetic risk status (P = 0·67). Treatment-induced MS tumour resolution was not affected by the presence of intramedullary disease (P = 0·61). The current study clarifies the prognosis of de novo isolated MS, in the context of AML.

Survival among patients with composite and sequential lymphoma between primary mediastinal lymphoma/diffuse large B-cell lymphoma and classical Hodgkin lymphoma: A population-based study.

BACKGROUND: Data on composite and sequential lymphoma between primary mediastinal lymphoma/diffuse large B-cell lymphoma (LBCL) and classical Hodgkin lymphoma (cHL) are rare. METHODS: We identified 25 cases with composite lymphoma (CL), 116 cases developing LBCL as a second primary cancer after cHL (cHL-LBCL), and 74 cases developing cHL as a second primary cancer after LBCL (LBCL-cHL) from the Surveillance, Epidemiology, and End Results (SEER) 18 database. Comparisons of overall survival (OS) and lymphoma cause-specific survival (CSS) between patients with cHL-LBCL or cHL-LBCL and their de novo counterparts were performed. RESULTS: The 5-year OS of patients with CL was 74.8 %. No significant difference in unadjusted OS and lymphoma CSS were observed between patients with de novo LBCL (LBCL-1 group) and patients with cHL-LBCL. However, the age- and stage-adjusted cHL-LBCL group had inferior OS and lymphoma CSS compared with that in the LBCL-1 group. The unadjusted and adjusted OS and lymphoma CSS in the LBCL-cHL group were significantly worse than patients with de novo cHL. CONCLUSIONS: CL between LBCL and cHL may have good outcomes. cHL survivors had poorer outcomes after a LBCL diagnosis versus patients with LBCL-1. Significantly poor outcomes were observed in patients with LBCL-cHL compared with patients with de novo cHL.

Survival analysis of patients with primary breast duct carcinoma and lung adenocarcinoma: a population-based study from SEER.

The appeal to enroll patients with primary breast and lung cancer in clinical trials is increasing, but survival of these two primary cancers remains to be elucidated. This study analyzed the prognosis of primary breast duct carcinoma with subsequent lung adenocarcinoma (BCLA) and primary breast duct carcinoma with prior lung adenocarcinoma (LABC). Cohorts of 3,515 patients with BCLA and 654 patients with LABC were identified from the Surveillance, Epidemiology, and End Results database. Patients were classified into simultaneous two primary cancer (sTPC), metachronous two primary cancer (mTPC1), or mTPC2 groups when the interval times between breast and lung cancer were within 6 months, between 7 and 60 months, or over 60 months, respectively. The propensity score matching program (PSM) was applied to determine the survival of BCLA/LABC relative to single breast/lung cancer. Cox proportional hazard regression model and competing risk modes were performed to identify confounders associated with all-cause and cancer-specific death, respectively. Survival of patients with LABC/BCLA relative to single breast/lung cancer was accessed via median survival time. The survival of patients with BCLA/LABC was generally poor compared with the survival of those with single breast cancer. The PSM-estimated HR in the sTPC group with BCLA and in the mTPC1 and mTPC2 groups with LABC were 0.75 (95% CI 0.62-0.90), 0.52 (95% CI 0.27-0.98), and 0.36 (95% CI 0.20-0.65), respectively, whereas the SHRs were 0.80 (95% CI 0.66-0.97), 0.68 (95% CI 0.34-1.34), and 0.46 (95% CI 0.27-0.80), respectively, compared with those in the single lung cancer group. By contrast, the survival rates of the remaining patients did not differ. The median survival times since secondary malignancy were 42, 23, and 20 months in the sTPC, mTPC1, and mTPC2 groups with BCLA, respectively, and 18, 60, and 180 months in those with LABC, respectively. For patients with BCLA, the adjusted Cox regression suggested incidences of all-cause deaths in mTPC1group were statically higher than those in sTPC group, whereas the incidences of all-cause and cancer-specific death in the mTPC1 and mTPC2 groups were statistically lower than those in the sTPC group. The prognosis of patients with breast cancer and subsequent lung cancer of over 18 months was not significantly different than that of single lung cancer, which supported the profound appeal to increase the involvement of these two primary cancers in potential beneficial clinical trials. For patients with lung cancer and prior breast cancer of within 6 months and subsequent breast cancer of over 18 months, prognosis was improved relative to single lung cancer. Therefore, additional attention is needed to eliminate the potential bias may when these patients are recruited in the clinical trials.

Therapeutic method for early-stage second primary non-small lung cancer: analysis of a population-based database.

BACKGROUND: Early-stage non-small lung cancer patients may survive long enough to develop second primary lung cancers. However, few studies have accurately described the therapeutic method, evaluation or prognostic factors for long-term survival in this complex clinical scenario. METHODS: Patients who had first and second primary non-small lung cancer in the Surveillance, Epidemiology, and End Results database between 2004 and 2015 were evaluated. Patients were included when their tumors were pathologically diagnosed as non-small lung cancer and in the early-stage (less than 3 cm and with no lymph node metastasis). Therapeutic methods were categorized as lobectomy, sublobectomy or no surgery. The influence of different therapeutic methods on the overall survival rate was compared. RESULTS: For the first primary tumor, patients who underwent lobectomy achieved superior survival benefits compared with patients who underwent sublobectomy. For the second primary tumor, long-term survival was similar in patients who underwent lobectomy and those who underwent sublobectomy treatment. The multivariate analysis indicated that age, disease-free time interval, sex, and first and second types of surgery were independent prognostic factors for long-term survival. Our results showed that the 5-year overall survival rate was 91.9% when the disease-free interval exceeded 24 months. CONCLUSION: Lobectomy for the first primary tumor followed by sublobectomy for the second primary tumor may be a beneficial therapeutic method for patients. If the disease-free interval exceeds 24 months, the second primary tumor will have no influence on the natural course for patients diagnosed with a first primary non-small lung cancer.

Prognostic Role of Tumoral PD-L1 and IDO1 Expression, and Intratumoral CD8+ and FoxP3+ Lymphocyte Infiltrates in 132 Primary Cutaneous Merkel Cell Carcinomas.

The association of immune markers and clinicopathologic features and patient outcome has not been extensively studied in Merkel cell carcinoma (MCC). We correlated tumoral PD-L1 and IDO1 expression, and intratumoral CD8+ and FoxP3+ lymphocytes count with clinicopathologic variables, Merkel cell polyomavirus (MCPyV) status, and patient outcomes in a series of 132 MCC. By univariate analyses, tumoral PD-L1 expression >1% and combined tumoral PD-L1 >1% and high intratumoral FoxP3+ lymphocyte count correlated with improved overall survival (OS) (p = 0.016, 0.0072), MCC-specific survival (MSS) (p = 0.019, 0.017), and progression-free survival (PFS) (p = 0.043, 0.004, respectively). High intratumoral CD8+ and FoxP3+ lymphocyte count correlated with longer MSS (p = 0.036) and improved PFS (p = 0.047), respectively. Ulceration correlated with worse OS and worse MSS. Age, male gender, and higher stage (3 and 4) significantly correlated with worse survival. MCPyV positivity correlated with immune response. By multivariate analyses, only ulceration and age remained as independent predictors of worse OS; gender and stage remained for shorter PFS. Tumoral PD-L1 expression and increased density of intratumoral CD8+ lymphocytes and FoxP+ lymphocytes may represent favorable prognosticators in a subset of MCCs. Tumoral PD-L1 expression correlated with intratumoral CD8+ and FoxP3+ lymphocytes, which is supportive of an adaptive immune response.

The effect of prior cancer on non-small cell lung cancer trial eligibility.

OBJECTIVES: Approximately 20% of patients diagnosed with non-small cell lung cancer (NSCLC) have a history of prior (non-lung) cancer. Patients with prior cancer are frequently excluded from clinical trials. We aimed to assess the potential impact of prior cancer on commonly used clinical trial endpoints. MATERIALS AND METHODS: Clinical trials of systemic therapy for incurable NSCLC from clinicaltrials.gov were reviewed to determine the frequency of exclusion on the basis of prior cancer. A cohort of patients with incurable NSCLC and prior cancer, treated with first-line systemic treatment at our institution were reviewed as a surrogate clinical trial population. A list of priori events was developed to capture the potential for prior cancer to negatively affect clinical trial conduct or endpoints. The proportions of patients that developed an outcome were assessed. RESULTS: Among trials registered on clinicaltrials.gov, 66% listed prior cancer in the eligibility criteria, and of these 35% excluded patients with prior cancer in the last 5 years. Of NSCLC patients treated with systemic therapy at Princess Margaret Cancer Center, 20% had prior cancer, of these, breast (20%) and prostate (19%) were the most common malignancies. Median time between prior cancer and NSCLC was 82 months. Median survival was 20 months. For patients without evidence of active prior cancer at baseline, and not on active therapy for prior cancer, no patients had evidence of a recurrence of prior cancer during the treatment and follow-up for the NSCLC, nor died from prior cancer. However, two patients developed new primaries. CONCLUSIONS: A history of prior cancer has a low likelihood of impacting clinical trial endpoints in patients with incurable NSCLC, if not active or requiring treatment. These findings should be validated in larger data sets.