Causes of long-term mortality in patients with head and neck squamous cell carcinomas

Purpose After treatment of a head and neck squamous cell carcinoma (HNSCC), patients with an adequate control of the tumor have a decreased overall survival when compared to age- and gender-matched controls in the general population. The aim of our study was to analyze the causes of long-term mortality in patients with HNSCC. Methods We carried out a retrospective study of 5122 patients with an index HNSCC treated at our center between 1985 and 2018. We analyzed the survival considering three causes of death: mortality associated with the HNSCC index tumor, mortality associated with a second or successive neoplasm, and mortality associated with a non-cancer cause. Results After the diagnosis of an HNSCC the most frequent cause of death is the head and neck tumor itself during the first 3.5 years of follow-up. Thereafter, mortality is more frequently associated with competing causes of death, such as second malignancies and non-cancer causes. Mortality associated with second and successive neoplasms was 2.3% per year, a percentage that was maintained constant throughout the follow-up. Likewise, mortality attributable to non-cancer causes was 1.6% per year, which also remained constant. There were differences in the mortality patterns according to the characteristics of the patients. Conclusion There are differences in the mortality patterns of patients with HNSCC depending on their characteristics. Knowledge of these patterns can help in the design of guidelines to improve the follow-up protocols of this group of patients to optimize the clinical cost-effectiveness.

Incidence of Second Malignancies in the History of Chronic Lymphocytic Leukemia

Introduction The occurrence of other neoplasms in patients diagnosed with chronic lymphocytic leukemia (CLL) is a known but insufficiently studied complication, highlighting the need for further research. Our study aims to analyze the incidence of other malignancies in CLL. Methods We performed a retrospective observational study of patients diagnosed with CLL between 2000-2016 at our center. Variables collected included: demographics, stage at diagnosis, treatment, response to treatment, death, other neoplasm (type, date of diagnosis, outcome), biomarker profiles studied by karyotyping, FISH, immunoglobulin heavy chain gene variable region mutational status, and TP53 mutational status. A descriptive study was performed. Quantitative variables are described as medians with their range, and qualitative variables as percentages. The relationship between qualitative variables and the development of second malignancies was performed using Chi-square and Fisher's exact test. Survival analyses were performed using the Kaplan-Meier method and the difference between groups was analyzed using the log-rank test. Results A total of 182 patients were evaluated, 104 men (57%) and 78 women (43%); median age: 74 years (39 - 97). Most patients were diagnosed at early stages (74% at Rai stage 0 and 84% at Binet stage A) and the median CIRS scale score at diagnosis was 4 (0 - 15). With a median follow-up of 76 months (20-212), 77/182 (42%) patients had received ≥1 line(s) of treatment: 1: 53%, 2: 26%, 3: 8%, ≥4: 13%. Forty-nine cases (27%) were reported with other malignancies in addition to CLL; cases with Richter transformation (n=5, 2.7%) were excluded. The diagnosis of CLL preceded the other neoplasm in 33/182 cases (18%): 8 hematologic and 27 non-hematologic neoplasms. Half of the hematologic malignancies involved MGUS (n=4), 1 mutated JAK2 (V617F) cMPN, 1 AML and 1 MALT lymphoma. As for non-hematologic tumors, non-melanoma skin cancer accounted for 30% of cases (n=8), followed by breast cancer (n=5, 18.5%). Neoplasms of the stomach, colon, liver, bladder and prostate together accounted for 37%, in the same proportion each (n=2, 7.4%). The remaining neoplasms corresponded to lung and bronchus, kidney, melanoma and pancreas. Five of the 27 patients had a third solid organ neoplasm, with non-melanoma skin cancer again being the most frequent (n=2). The other neoplasms were lung, small bowel and thyroid. The incidence of second neoplasms was higher in treated patients (26% vs. 12.4%, p=0.019). The incidence of a second hematologic malignancy was related to treatment administration (9%) compared to 1% in untreated patients (p=0.011), especially in those with ≥ 3 lines (37.5% vs. 3%), p=0.024. We could not find any association between the variables analyzed and the development of second non-hematologic malignancies. The development of second neoplasms after the diagnosis of CLL did not have a negative impact on the overall survival of these patients. Conclusions The incidence of second malignancies is high in patients with CLL, being higher in those patients who have received treatment, and especially in those with a greater number of lines received. In contrast, the development of solid tumors did not seem to be affected by treatment administration, which should motivate further investigation in specific subgroups of patients. In our series, the development of second neoplasms after the diagnosis of CLL did not have a negative impact on the overall survival of these patients. Disclosures Gonzalez-Lopez: Novartis: Other: Advisoryboard and speakers honoraria, Research Funding; Amgen: Other: Advisory board and speakers honoraria, Research Funding; Sobi: Other: Advisory board honoraria; Grifols: Other: Advisory board honoraria.

Detailing the epidemiological and clinical characteristics of chronic lymphocytic leukaemia in Portugal—Results from a population-based cancer registry cohort study

Background Chronic lymphocytic leukaemia (CLL) is the most common leukaemia among adults in western countries. Considering the increasing incidence and prevalence of this condition, it is highly relevant to better characterise these patients in Portugal, where data is still scarce. Methods To determine incidence, clinical presentation, survival and second malignancies, a population-based historical cohort study was conducted. Cases of interest were identified through the South Region Cancer Registry database and additional data sources. Patients aged ≥18 years, with a confirmed diagnosis of CLL or small lymphocytic lymphoma between January 1st, 2013 and December 31st, 2014 were included. Patients were followed‐up until death or cut-off date (December 31st, 2019). Results A total of 496 patients were included and median follow-up time was 5.46 years. Crude incidence rates were 5.03 and 5.22 per 100,000 inhabitants for 2013 and 2014, respectively, and age-adjusted incidence rates were 3.18:100,000 European population for 2013 and 3.35:100,000 European population for 2014. Median age at diagnosis was 71 years and the male/female ratio was 1.40. The majority of patients had leukemic presentation of the disease (86.09%), was diagnosed in Binet stage A (75.58%) and did not present B symptoms (84.01%), anaemia (haemoglobin ≤10g/dL; 90.63%) nor thrombocytopenia (platelet count ≤100 000/μL; 91.73%). Five-year overall survival (OS) rate was 70.53% (95%CI 66.31–74.34) and age, lactate dehydrogenase, Binet stage and a ≥5 Charlson comorbidity index score were independently associated with OS. Standardised-incidence ratios for any second malignancy and cutaneous squamous cell carcinoma were 1.59 (95%CI 1.19–2.08) and 10.15 (95%CI 6.28–15.51), respectively. Conclusion Incidence, clinical presentation and survival of CLL Portuguese patients are similar to those reported for other western countries. The increased risk of second malignancies raises concerns and needs adequate clinical watchfulness.

Second malignancies in children with head and neck primary tumors.

e22014 Background: Children with primaries in the head and neck region, especially those who recieve radiotherapy (RT) are at increased risk for second malignancies (SM). This study aims to assess the incidence and outcome of SM in children with head and neck primary tumors. Methods: During 1990-2017, 3214 children with cancer were treated in theIstanbul University, Oncology Institute. The primary tumor was in the head and neck region in 1414 (651 brain tumors,289 retinoblastoma,474 other). Survivors followed up for at least 3 years from diagnosis were evaluated for second malignancies. Results: 30 SM were identified in 28 survivors (18 male,10 female) at a median of 12 years (2-26) from diagnosis. The primary diagnosis was nasopharyngeal carcinoma (NPC) in 8, bilateral retinoblastoma (RBS) in 7, embryonal brain tumors (CNST) in 8, Hodgkin lymphoma (HD) in 3, rhabdomyosarcoma(RMS) in 2. Two RBS patients who did not recieve radiotherapy developed pilocytic astrocytoma (at 2 years) and osteosarcoma of the extremity (at 4 years) each, both are alive with no evidence of disease (NED) for 3.5 and 10 years. 26 patients recieved RT: one with CNST developed MDS (at 8 years) and died due to complications after stem cell transplantation (SCT). One with NPC developed PNET of the bladder (at 5 years) and died of disease (DOD). One with relapse HD developed Langerhans cell histiocytosis 2 years after SCTand is with NED for 10 years. The other 23 developed SM in the/proximity of the RT field. These SM were 7 sarcomas (in 4 retinoblastoma,2 NPC, 1 RMS), 6 thyroid cancer (in 2 CNST, 1 RMS, 1 HD, 1 NPC), 3 meningiomas (in 2 CNST, 1 RBS), 5 carcinomas (in 4 NPC, 1 RBS), 1 basal cell carcinoma (in a recurrent re-irradiated CNST, is with NED), 1 peripheral nerve sheath tumor (in 1 HD, DOD), glioblastoma multiforme and non Hodgkin's lymphoma (in the same CNST case, DOD at 6 months). One of the NPC case developed both sarcoma (at 18 years) and carcinoma (at 25 years, NED). The RT dose (20-70 Gy) differed according to diagnosis. All survivors of thyroid cancer are with NED except one who died in an accident; of 3 meningiomas, the one with retinoblastoma who developed malignant meningioma died. Of five carciinomas as SM, two with NPC who developed carcinomas died. Of sarcomas as SM, two with fibrosarcomas are with NED at 10 years each (1NPC, 1 RMS). All patients survived for a median of 3 (0.5-16) years after SM; 16/28 (57%) are with NED at a median of 8 (1-16) years; 12 died at a median of 1.8 (0.5-4.75) years after SM. (1 CNST due to accident, 1 NPC due to infectious complications after a reconstructive surgery, 10 DOD). All SM were detected early during regular surveillance. Conclusions: Children with head and neck primaries are at risk for SM which may occur many years later, especially in RT sites. RT should be avoided when possible such as currently in RBS. Patients need regular surveillance lifelong, for early detection of SM. SM should be treated with curative intent, to achieve long term survival.

Thymic Carcinomas and Second Malignancies: A Single-Center Review

Thymic carcinomas account for less than 0.01% of new cancer diagnoses annually and are more aggressive than thymomas. Autoimmune disorders have been associated with thymomas and only recently with thymic carcinomas. Second malignancies are well described after thymomas. The aim of this study was to analyze the incidence of second malignancies in patients with thymic carcinomas. All cases of thymic carcinomas were identified from the pathology archives of Indiana University. Histological materials were reviewed and further correlated with clinical data to identify incidence of second cancers in patients with thymic carcinomas. Histological material was available for review in 92 cases of thymic carcinoma. Clinical data were available for 85 patients. Fourteen of these (16.5%) patients had a second malignancy; these included small cell lung carcinoma, “testicular cancer”, embryonal carcinoma, seminoma, breast carcinoma (two cases), prostatic adenocarcinoma, Hodgkin’s lymphoma, thyroid carcinoma, bladder carcinoma (two cases), renal cell carcinoma, and melanoma. The latter could precede, be concurrent with, or follow the diagnosis thymic carcinoma. The incidence of second cancers in patients with thymic carcinomas is similar to that reported for thymomas. Abnormalities in immunological surveillance may be responsible for this high incidence of second malignancies in thymic tumors.