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The most important challenges in acute promyelocytic leukemia (APL) is preventing early death and reducing long-term events, such as second neoplasms (s-NPLs). We performed a retrospective analysis of 2670 unselected APL patients, treated with PETHEMA "chemotherapy based" and "chemotherapy free" protocols. Only de novo APL patients who achieved complete remission (CR) and completed the three consolidation cycles were enrolled into the analysis. Out of 2670 APL patients, there were 118 (4.4%) who developed s-NPLs with the median latency period (between first CR and diagnosis of s-NPL) of 48.0 months (range 2.8–231.1): 43.3 (range: 2.8–113.9) for s-MDS/AML and 61.7 (range: 7.1–231.1) for solid tumour. The 5-year CI of all s-NPLs was of 4.43% and 10 years of 7.92%. Among s-NPLs, there were 58 cases of s-MDS/AML, 3 cases of other hematological neoplasms, 57 solid tumours and 1 non-identified neoplasm. The most frequent solid tumour was colorectal, lung and breast cancer. Overall, the 2-year OS from diagnosis of s-NPLs was 40.6%, with a median OS of 11.1 months. Multivariate analysis identified age of 35 years (hazard ratio = 0.2584; p < 0.0001) as an independent prognostic factor for s-NPLs. There were no significant differences in CI of s-NPLs at 5 years between chemotherapy-based vs chemotherapy-free regimens (hazard ratio = 1.09; p = 0.932). Larger series with longer follow-up are required to confirm the potential impact of ATO+ATRA regimens to reduce the incidence of s-NPLs after front-line therapy for APL. [ABSTRACT FROM AUTHOR]

Simple Summary: Testicular cancer is characterized by an excellent prognosis; long survival, however, requires careful monitoring, also due to the possibility of developing second tumors. Seminoma has a better prognosis, even many years after diagnosis, but also a greater possibility of developing second tumors. Non-seminoma presents an increased risk, especially among patients over 40. This study investigated the incidence, mortality, and 5-year survival rates of testicular cancers diagnosed in a northern Italian province, which were eventually associated with previous or subsequent extratesticular neoplasms. Cases from 1996 to 2020 were examined by age and histotype (seminoma vs. non-seminoma). The standardized incidence rate was calculated using the European population, and the annual percent change (APC) was reported. The five-year relative survival was estimated using the Pohar Perme method. The association with the second neoplasm was also evaluated. In our study, 385 patients with testicular cancer were included, most of whom were aged between 30 and 40 years. The non-seminoma and seminoma groups accounted for 44% and 18% of younger adults, respectively. The incidence rate increased during the study period (APC 1.6*); however, it increased in seminomas (APC 2.3*) but not in non-seminomas (APC −0.1). Conversely, the mortality rate remained constantly low either overall or in each of the two groups. The overall 5-year survival rate of testicular cancer patients was 95% (99% and 88% for seminomas and non-seminomas, respectively). Primary extratesticular tumors were documented in 37 cases, 18 after and 19 before the testicular cancer diagnosis. Our study confirms that the increased incidence and excellent survival rate are the prerogative of seminomas. [ABSTRACT FROM AUTHOR]

This article presents the international dataset of cases in which the association of Langerhans cell Histiocytosis (LCH) with other malignancies (AM) was documented occurring at any age before, concurrently or after LCH. These data are mostly derived from previously published manuscripts or from completed case report forms (CRFs) by Histiocyte Society (HS) members or colleagues. In particular, for each case of LCH-AM, the database reports all the available data about clinical and biologic characteristics of the two tumors, as well about treatment and status at follow-up. The AM were categorized as: i) leukemias [acute lymphoblastic or myeloid leukemia (ALL and AML, respectively), other leukemias] and myeloproliferative disorders; ii) lymphomas [Hodgkin lymphoma (HL) and non-Hodgkin lymphomas (NHL)] and iii) solid tumors.A total of 270 LCH-AM cases were documented, of which 116 (43%) occurred among children. After stratification by age at LCH diagnosis, using 18 years as cut-off between children and adults, we here provide details on the clinical characteristics in terms of LCH system involvement and affected organs, as well on the temporal relationship between the LCH and AM diagnoses, including details on the AM malignancy types. In 19 cases the LCH and the corresponding AM occurred in a different age group.The data set is available for future studies in view of new insights of the genetic or environmental determinants of LCH and/or of treatment related subsequent neoplasms.

Background: Autologous blood or bone marrow transplantation (aBMT) is considered the standard of care for patients with multiple myeloma (MM). Significantly improved survival necessitates an understanding of the morbidity burden borne by the growing survivor population.Methods: The authors evaluated severe and/or life-threatening chronic health conditions (CHCs) and subsequent neoplasms (SNs) in patients with MM who were treated with aBMT using the Bone Marrow Transplant Survivor Study. A total of 630 study participants had undergone aBMT for MM at 1 of 3 BMT centers, had survived ≥2 years after aBMT, and were aged ≥18 years at the time of survey completion. Survivors of aBMT identified 289 nearest-age siblings to constitute an unaffected comparison group. Scoring of CHCs was based on version 5 of the National Cancer Institute Common Terminology Criteria for Adverse Events to determine severity (with grade 3 indicating serious and grade 4 indicating life-threatening).Results: The 10-year cumulative incidence of any grade 3 to 4 CHC among survivors of aBMT was 57.6 ± 3.2%. Survivors of MM were found to be at 40% higher odds of developing grade 3 to 4 CHCs when compared with siblings (95% confidence interval [95% CI], 1.0-1.9). Among SNs, 96% were solid tumors, yielding a 10-year cumulative incidence of 13.6% ± 2.5%. Pre-aBMT exposure to cyclophosphamide (hazard ratio [HR], 3.5; 95% CI, 1.5-8.1) and immunomodulatory drugs (HR, 3.9; 95% CI, 1.5-10.1) were associated with an increased risk of solid tumors. Melanoma (10-year cumulative incidence: 3.3% ± 1.2%) and squamous cell carcinoma (10-year cumulative incidence: 5.1% ± 1.8%), were the most common SNs. Pre-aBMT exposure to cyclophosphamide (HR, 6.02; 95% CI, 1.4-26.1) and immunomodulatory drugs (HR, 7.9; 95% CI, 0.9-68.5) was associated with an increased risk of melanoma.Conclusions: The 10-year cumulative incidence of severe and/or life-threatening CHCs was found to approach 60% in long-term survivors of MM, with solid SNs constituting a large morbidity burden. The current study has provided evidence supporting the close monitoring of survivors to manage morbidity. [ABSTRACT FROM AUTHOR]

Rates of childhood cancer survival in developed countries have risen to over 80-85 %. In consequence, the population of childhood cancer survivors (CCS) has grown considerably. Nevertheless, CCS present a high morbidity and mortality due to cancer or its treatment, with an increased risk of premature mortality, second primary tumors and late side effects, both physical and psychosocial, all of which decrease the quality of life. Long-term follow-up (LTFU) of CCS is recommended to prevent, detect and treat those health problems. Despite the advances achieved, the management of CCS is still not optimal. Among the areas for improvement discussed in this manuscript are: (1) Quantifying the real burden of morbimortality, by implementing new frequency measures (mean cumulative count and cumulative burden), to obtain more accurate assessments, and using simulation models, to determine individual risks; (2) Assessing the impact of risk factors for late side effects, related to the patient, tumor type, treatments, lifestyle, comorbidities, genetics and ageing; (3) Considering the impact of the international harmonisation of long-term follow-up guidelines, to generate homogeneous, evidence-based recommendations and an individualized LTFU and, (4) Challenges to LTFU implementation, considering models of care adapted to patient risk and needs, with special attention to the transition to adult-care follow-up. Finally, we comment on the situation of CCS in Spain and consider future prospects for improving the health and quality of life of this population., (Copyright © 2024 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Free-flap reconstruction for recurrent head and neck cancer may be challenging depending on the previous treatments, those are, chemotherapy, radiotherapy, and surgery, including neck dissection or free tissue transfer. Specifically, the previous treatment could compromise the neck vessels, thereby making free-flap reconstruction more difficult. This study aimed to investigate the correlation between previous treatments and vascular compromise of the free flap. Methods: In this retrospective study, 124 free-flap reconstructions in 116 patients for recurrent head and neck cancer between 1993 and 2017 were investigated. The demographic characteristics, previous treatments, flap choices, infections, recipient vessels, and vascular crises were evaluated. Results: Of the 124 reconstruction cases, 10 had vascular crises. There were six revisions, totaling six flap failures. The success rate of free-flap reconstruction for recurrent cancer was 95.2%, which significantly differed from that for primary cancer (98.8%, p= 0.006). Moreover, in the recurrent cancer group, no correlation was found between previous treatments and vascular crises (p> 0.05). Increased rates of contralateral or uncommon anastomoses were found following neck dissection (p< 0.05). Conclusion: Previous neck dissection or radiotherapy could lead to scarring and tissue damage, which could in turn make microvascular reconstruction more challenging; however, the effect was not definite in this study. Approximately 60% of patients with previous neck dissection had compromised ipsilateral recipient vessels, which resulted in contralateral or uncommon anastomoses. In this study, free-flap reconstruction seems to be quite safe and preferable in patients with recurrent head and neck cancer based on the overall survival rate. [ABSTRACT FROM AUTHOR]

Background: Previous studies have reported increased risk of second cancer in both esophageal squamous cell cancer (ESCC) and esophageal adenocarcinoma (EAC) survivors. This study aimed to examine the risk and influential factors of second cancer in ESCC and EAC patients., Methods: This population-based cohort study included 7,297 ESCC patients and 11,812 EAC patients who were in 1992-2019 from the Surveillance, Epidemiology, and End Results (SEER) program in the United States. These patients were followed up until diagnosis of second cancer, death, or end of the study (December 31, 2019). We calculated standard incidence ratio (SIR) and 95% confidence interval (CI) of second cancer and performed competing-risk regression to estimate the subdistribution hazard ratios (sHR) comparing categories of patients' characteristics., Results: After a total of 49,509.38 person-years of follow-up, 431 (5.9%) ESCC patients and 636 (5.9%) EAC patients developed a second cancer. An overall increased risk of second cancer was observed in both ESCC patients (SIR: 1.66, 95% CI: 1.51-1.83) and EAC patients (SIR: 1.11, 95% CI: 1.02-1.20). ESCC patients were at increased risk of second malignancy in oral cavity and pharynx (SIR: 12.57, 95% CI: 9.87-15.79), stomach (SIR: 3.03, 95% CI: 1.77-4.85), nose and larynx (SIR: 4.79, 95% CI: 2.47-8.37), and lung and bronchus (SIR: 2.44, 95% CI: 1.96-2.99), but decreased risk of prostate cancer (SIR: 0.73, 95% CI: 0.52-0.99). EAC patients had increased risk of second malignancies in stomach (SIR: 4.41, 95% CI: 3.23-5.89), lung and bronchus (SIR: 1.26, 95% CI: 1.02-1.54), and kidney (SIR: 1.57, 95% CI: 1.05-2.25). The risk of second cancer was higher in female ESCC patients than in males (sHR: 1.34, 95% CI: 1.11-1.63) and decreased with more advanced tumor stage in both ESCC patients (sHR: 0.62, 95% CI: 0.50-0.76 for regional stage; sHR: 0.27, 95% CI: 0.20-0.36 for distant stage) and EAC patients (sHR: 0.47, 95% CI: 0.40-0.56 for regional stage; sHR: 0.10, 95% CI: 0.07-0.13 for distant stage)., Conclusions: Both ESCC and EAC patients are at considerable risk of certain types of second cancer., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tgh.amegroups.com/article/view/10.21037/tgh-23-29/coif). XQ receives funding support from Haiyan Foundation of Harbin Medical University Cancer Hospital (No. JJMS2022-20). YF receives funding support from National Natural Science Foundation of China (No. 72174048). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The other authors have no conflicts of interest to declare., (2023 Translational Gastroenterology and Hepatology. All rights reserved.)

Purpose: The identification of experienced and knowledgeable dental specialists to provide appropriate oral care for cancer patients, as well as the integration of this care within general oncology management, may be a challenge. This paper discusses the general and additional requirements for dental care providers to support the cancer patient and provide prevention and/or treatment for oral complications of cancer therapy. Methods: We performed a literature review of specific issues regarding the oral cavity and adjacent structures in the cancer patient, including detection and early diagnosis of oral malignancy. We incorporated the systemic effects of cancer and its therapy that affect oral disease and treatment. We present a summary of how to seek expert dental care for cancer patients and for referral from the dental and medical community. Results: Due to the complexity conferred by the disease and its treatment, cancer patients require educated, experienced dentists for treatment and/or prevention of oral-related morbidity. Correct diagnosis and evidence-based prophylactic and therapeutic oral care can significantly improve patient quality of life and reduce morbidity and healthcare costs. Conclusions: The knowledge and expertise of dental professionals regarding prevention/treatment of complications and secondary malignant lesions in cancer patients are critical. Integration of oral care with the oncology care and in survivors requires effective communication between dental and medical providers beginning ideally at diagnosis. These clinicians may be identified at the cancer center, nearby hospital dental programs, and, less commonly, in the community. [ABSTRACT FROM AUTHOR]

Survival after non-Hodgkin lymphoma ( NHL) has increased thanks to improved treatment but NHL survivors have an increased risk of second neoplasms. The assessment of cancer risk patterns after NHL may help to quantify the late side-effects of therapy. Poisson regression was used to estimate relative risks ( RRs) and absolute incidence rates for nine solid tumours based on a nationwide cohort of 60 901 NHL survivors from Finland, Norway and Sweden. Patients were diagnosed between 1980 and 2006 and developed 6815 s neoplasms. NHL patients showed an increased risk of each of the nine investigated cancer sites: prostate and pancreas (both RRs 1·28), breast (1·37), colorectum (1·48), urinary bladder (1·52), stomach and lung (both RRs 1·87), skin (melanoma 2·27) and kidney (2·56). The RRs showed a U-shaped relationship with time after NHL for all nine-second cancer types. NHL diagnosis early in life was a risk factor for the development of second cancers with the exception of melanoma, but a risk excess was even observed in patients diagnosed with NHL at age 80+ years. The present study provides accurate estimates on the adverse late effects of NHL therapy, which should guide the establishment of cancer prevention strategies in NHL survivors. [ABSTRACT FROM AUTHOR]

Genetic factors are important for developing primary and subsequent malignancies in children. This study investigated the role of genetic factors involved in DNA-repair. Designed as a feasibility study, it addressed the possibility of obtaining samples for genetic analyses from former patients through the German Childhood Cancer Registry. Testing feasibility was as important as the biological question itself. We analyzed the expression of DNA-repair genes in untreated primary fibroblasts of 20 individuals with a second neoplasm compared to 20 matched single neoplasm cases using customized cDNA microarrays (1344 gene sequences, about 800 genes). Matching was by first neoplasm, age, and year of first diagnosis. Forty-six percent of the 52 contacted second neoplasm cases and 18% of the 132 single neoplasm patients participated in the study. The DNA-repair gene results showsmall differences in the basal gene expression of FTH1 and CDKN1A. To our knowledge, this is the first study using gene expression arrays in untreated primary fibroblasts regarding second neoplasms after a childhood neoplasm.We were able to recruit childhood cancer patients for genetic analyses long after diagnosis. The biological importance of the differences in the DNA-repair gene expression has to be elucidated yet. [ABSTRACT FROM AUTHOR]

Hereditary retinoblastoma (Rb) is a high penetrance autosomal dominant disease showing not only an increased risk of suffering bilateral Rb but also other second neoplasms. However, some families show a low-penetrance phenotype with reduced expressivity and incomplete penetrance of the retinoblastoma gene ( RB1). Given the lack of specific guidelines for the follow-up of adult patients with hereditary Rb, the authors present a case report of a family with a low-penetrance phenotype and review the recommended surveillance in this setting, stressing the difficulties found in the genetic counselling process and follow up. Thus, since patients are at an increased risk, lifelong regular medical surveillance to detect any second malignancy at a stage that can be cured is required. In addition, avoidance of DNA-damaging agents and genetic testing should be considered for a throughout management of these families. [ABSTRACT FROM AUTHOR]

To study the characteristics and clinical features of uterine neoplasms developed after radiation therapy for cervical carcinoma. Clinical data of 47 cases of uterine neoplasms occurred following radiation therapy for cervical carcinoma were retrospectively reviewed. The median age at uterine neoplasms diagnosis was 62 years (range: 38–77 years), and the median latency period from initial therapy to development of uterine neoplasms was 14 years (range: 5–35 years). Thirty of 47 cases were endometrial carcinoma, of which 3 were uterine papillary serous carcinoma (UPSC). Seventeen of 47 patients were uterine sarcoma, all of those were carcinosarcoma. The distribution by stage, grade, and histology of 30 cases of endometrial carcinoma was as follows: stage Ib, 1 case; stage Ic, 2 cases; stage II, 6; stage IIIa, 4; stage IIIb, 2; stage IIIc, 11; stage IV, 4 cases; grade 1, two cases; grade 2, nine; grade 3 (include 3 UPSC patients), seventeen; unknown grade, two; endometriod, 27; UPSC, 3 cases; 7 of 30 cases of endometrial carcinoma had recurrences (23.3%), at median time to recurrence was 24 months, and their median survival time was 26 months. The overall 3- and 5-year survival rates were 60% and 38%, respectively. Of the 17 cases of uterine sarcoma, the median survival was 10 months, 6 patients occurred recurrence (35.9%), at a median time to recurrence was 9 months, and their median survival was 6 months. The overall 3- and 5-year survival rates were 12% and 0, respectively. The main uterine neoplasms development after radiation therapy for cervical carcinoma is endometrial carcinomas, of which there is a preponderance of high-risk histological subtypes and a poor prognosis. Most of the uterine sarcomas occurred following radiation therapy for cervical carcinoma are carcinosarcomas and the prognosis is very poor. [ABSTRACT FROM AUTHOR]

With improvements in survival among individuals diagnosed and treated for cancer there is an increasing recognition of the risk of long-term adverse effects of therapy. Second neoplasms represent one of the more serious late effects of treatment and are associated with a substantial level of morbidity and mortality. Survivors of childhood cancers, because of their potential longevity, are at particular risk for this adverse outcome. The Childhood Cancer Survivor Study is a large cohort consisting of adult survivors of childhood cancer diagnosed and treated between 1970 and 1986. The CCSS has provided important data to quantify radiation-associated risk for subsequent cancers including neoplasms of the breast, thyroid and central nervous system. [ABSTRACT FROM AUTHOR]

Several surveys have defined chronic lymphocytic leukemia (CLL) patients as a high-risk patient population for developing second neoplasms. As possible mechanisms underlying the increased risk of specific second malignancies in CLL patients the immunodeficiency associated with disease is generally proposed. As far as secondary acute leukemia is concerned, greater insight into the molecular pathogenesis of therapy-related acute myeloid leukemia (AML) developing in CLL would allow to avoid treatment regimens that can lead to this complication. Richter's syndrome continues to be a fatal and highly refractory to chemotherapy disease complicating the clinical course of CLL. Therefore, experimental approaches of therapy should be considered in its treatment. Given the prolonged survival of patients with CLL, it is important to recognize early a second cancer especially whether new symptoms or physical findings arise. [ABSTRACT FROM AUTHOR]

: AimFamilial cases of Kaposi’s sarcoma (KS) are rare, and have all been described in patients with the classical variant of the disease. The predisposition of classical Kaposi’s sarcoma among Jews is well known. We herein describe five families, all Jews, in which two members have Kaposi’s sarcoma. To our knowledge, this has been the largest reported series of familial Kaposi’s sarcoma.: Patients and methodsThe clinical course, management and response to therapy were described and compared with other published cases.: ResultsNo similarity was found in any of the families in time and age of onset of the disease, or in the severity and course of the disease among the members of the same family. There was a high incidence of second neoplasms among these familial cases.: ConclusionsWe discuss the potential implications of second neoplasms based on our understanding of the pathogenesis of the disease, as well as the influence or predisposal of some genetic mechanisms to the development of Kaposi’s sarcoma. [Copyright &y& Elsevier]

: PurposeTo estimate the incidence and types of second neoplasms in survivors of childhood and adolescent cancer, as well as the characteristics of those who developed second neoplasms.: MethodsSurvivors who were under age 21 years at initial diagnosis, off therapy, and in remission for 2 years are referred to the Long Term Survivors'' Clinic (LTSC) at Children''s National Medical Center (CNMC). This review includes patients entered in the clinic database from January 1, 1997 to August 30, 2002.: ResultsTwenty-three (2.3%) of 987 childhood cancer survivors followed in the LTSC had 26 (2.6%) second and third neoplasms. The mean age was 6.7 years at initial diagnosis, 20.3 years at diagnosis of the second neoplasm, and 20.5 years at diagnosis of the third neoplasm. Of 10 female and 13 male patients, 15 were white, six black, one Hispanic, and one Asian. All but two of the patients received radiation. Nineteen neoplasms, including seven thyroid carcinomas, six central nervous system tumors (three meningiomas), three basal cell carcinomas, two breast cancers, and one soft tissue sarcoma, occurred at sites within or contiguous to radiation sites. Five patients died, but the majority of neoplasms were treatable and most patients had good outcomes.: ConclusionIndefinite follow-up in a long-term survivors'' clinic is indicated for adolescent and adult survivors of childhood cancer, with routine examination and screening for recurrence of the initial cancer as well as late effects, including second neoplasms. [Copyright &y& Elsevier]

We performed a randomized clinical trial to assess the usefulness and toxicity of combined therapy compared with chemotherapy and radiotherapy in the treatment of early stage Hodgkin‘s disease with bulky disease as an adverse prognostic factor. Three-hundred and seven patients were enrolled into the study. They were randomized to receive either radiotherapy (extended field, generally mantle, 3500 cGy), or chemotherapy (adriamycin, bleomicin, vinblastine and dacarbazine: ABVD, 6 monthly) cycles or combined therapy (three cycles of ABVD, followed by irradiation therapy and three more cycles of chemotherapy). The median follow-up duration from start of treatment was 11.4 years. Complete response rates were similar in the three arms: 83% for radiotherapy (95% confidence interval [CI] 67–92%), 80% for chemotherapy (CI 69–88%) and 87% for combined therapy (CI 74–94%). However, disease-free survival and overall survival were better in the patients treated with combined therapy. At 12 years 76% (CI 51–93%) of the patients treated with combined therapy remained alive in the first complete remission compared with 42% (CI 26–61%) in patients treated with radiotherapy and 48% (CI 31–57%) in patients who had received chemotherapy alone (P < 0.01). Improvement in overall survival was also evident at 12 years: 88% (CI 59–93%) in those who had received combined therapy, compared with 53% (CI 36–67%) in the radiotherapy arm and 59% (CI 35–67%) in the chemotherapy group. Acute toxicity was more frequent in patients treated with combined therapy, but no death related treatment was observed in the three groups. Late toxicity was similar in the three treatment groups. Combined therapy with extended field radiotherapy and six cycles of chemotherapy is an effective treatment of patients with early stage bulky Hodgkin‘s disease compared with chemotherapy or radiotherapy alone. [ABSTRACT FROM AUTHOR]

We report a retrospective study about the incidence of second neoplasms (SN) in patients affected by chronic lymphocytic leukemia (CLL) admitted to Padua Hospital between 1989 and 1991, comparing data with those of a similar population. We examined the records of 212 patients, finding in 19 of them 22 second neoplasms; the most common kind was lung cancer. There was an increased incidence of SN, without statistic significance if compared with all sites of cancers in the general population, especially during the first 2 years from the diagnosis of CLL. In accordance with the majority of authors, there is an unknown connection between the two diseases, but certainly independent of chemotherapy with alkylating agents. [ABSTRACT FROM AUTHOR]

Objective: To analyse the incidence of appearance of second and successive neoplasms in a cohort of head and neck squamous carcinoma patients., Material and Methods: We conducted a retrospective study with 4,458 patients with an index tumour located in the head and neck diagnosed during the 1985-2016 period. We evaluated the incidence of appearance of second neoplasms and successive neoplasms over a period of 30 years., Results: During the follow-up, 1,203 patients (27.0%) had a second neoplasm, 242 patients (5.4%) a third neoplasm, 58 patients (1.3%) a fourth neoplasm, and 8 patients (0.2%) 5 or more successive neoplasms. The incidence of appearance of second neoplasms was 3.5% per year, remaining relatively constant throughout the follow-up period. The patients with a second neoplasm had a higher risk of appearance of a third neoplasm, and those with a third neoplasm had a higher risk of a fourth. Seventy-eight percent of the second neoplasms, 88% of the third neoplasms, and 89.6% of the fourth neoplasms appeared in locations epidemiologically related to tobacco and alcohol use., Conclusions: Second neoplasms after a head and neck index tumour appeared at a constant rate of 3.5% per year throughout the entire follow-up period., (Copyright © 2019 Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. Publicado por Elsevier España, S.L.U. All rights reserved.)