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Childhood acute lymphocytic leukemia with a second primary neoplasm.

The occurrence of de novo cancer in renal transplant patients who have received immunosuppressive therapy has been noted. An increased incidence of second primary neoplasm (SPN) has been reported in adults with various forms of cancer. The incidence of SPN in childhood cancer is lower. Successful therapy in several childhood cancers has resulted in prolonged disease-free survival time with the opportunity for longer patient-years of observation. The development of a SPN, an astrocytoma, in a child with continuous complete remission for more than 6 years is reported. The incidence of SPN in childhood cancer needs to be established.

Adult

Second primary neoplasms following ovarian cancer.

Follow-up surveys of patients with ovarian cancer revealed an increased risk of second primary cancers of the uterine corpus, colon, bladder, breast, and hematopoietic system. The excess risk or uterine corpus cancer was independent of therapy. The risk of colon cancer was increased in all treatment groups but was especially high among patients receiving radiation or chemotherapy. The predisposition to other neoplasms was limited to certain treatment groups: bladder cancer to irradiation, leukemia to chemotherapy, and lymphoma to either modality. The pattern of second neoplasms following ovarian cancer appears to be influenced by therapy as well as by common etiologic factors.

Alkylating Agents

Oncogenesis and other late effects of cancer treatment in children.

Review of hospital charts of 168 patients surviving two or more years following the diagnosis of cancer and subsequent-examinations of 40 of these patients yielded these observations: (a) Hospital charts were adequate to ascertain the number of second primary neoplasms. Three malignant and eight benign tumors were found, an incidence of 6.5%. (b) The three patients with second malignant neoplasms did not receive chemotherapy and two of three were treated with radiation. (c) Abnormalities other than second neoplasms, which may have been delayed consequences of treatment, were infrequently noted in hospital records, but were subsequently detected on specific examinations.

Antineoplastic Agents

Differences of clinical features, prognosis and genetic mutations in Chinese patients with malignant melanoma and additional primary tumours.

BACKGROUND: The differences in the clinical features, prognosis and genetic mutations in Chinese patients with malignant melanoma (MM) and additional primary tumours remain unclear. METHODS: A retrospective analysis was conducted on patients with malignancies in Fujian Cancer Hospital from January 2007 to September 2022, end follow-up in September 2023. Clinical data were gathered, survival analysis was performed, and genetic mutations were detected. RESULTS: There were 58 of 1223 melanoma patients with melanoma and additional primary tumours, an incidence of 4.74%. Acral MM was the most common subtype (26/58), 23 (39.66%) patients had concomitant digestive tumours. Patients who had MM as their first primary tumour (MMFP) had shorter tumour occurrence intervals (9.93 vs. 57.78 months, p = .008) but longer melanoma survival (MM-OS) than the non-MMFP group (100.43 vs. 18.93 months, p = .015). Patients with cancer family histories were more likely to have pathogenic and likely pathogenic (P/LP) mutations (2/5 vs. 4/25). The somatic BRAF gene mutation was frequently observed in MM tissue (8/19, 42.11%). Three patients had whole-genome doubling and microsatellite instability-high (MSI-H). The COSMIC2 signature 3 was significantly higher in the P/LP group. CONCLUSIONS: The frequency of MM and additional primary tumours is about 5% in Chinese populations. Patients with melanoma diagnosed first have longer melanoma survival. Digestive system tumours were the most concomitant; a digestive examination is advisable, especially for those with an expected overall survival (OS) greater than 10 months. Meanwhile, patient's family cancer history should be followed up in detail, along with completion of germline P/LP mutation and somatic mutation testing, all of which may provide valuable support for further treatment.

Adult

Effect of postoperative wound infection on the course of stage II melanoma.

Microbial infections reportedly have a favorable effect on the course of certain malignant diseases. Intralesional inoculation of micro-organisms can bring about tumor regression in certain clinical and experimental situations. In order to evaluate the influence of immediate postoperative wound infection on the course of Stage II melanomas, a retrospective study was undertaken of 211 patients who had undergone axillary or groin dissection. None had any antibiotic, steroid, chemoimmunotherapy, or cryosurgery and there was no history of a second primary neoplasm, pregnancy, immunodeficiency, or administration of immunosuppressive drugs. Forty of these patients developed significant postoperative wound infections. Although their representation according to sex, tumor location, number of nodes involved, and other parameters was comparable to that of the remaining 171 patients who did not develop wound infections, the incidence of local recurrence in the group with infections was significantly lower (p less than 0.01). Patient survival and disease-free interval following node dissection were not influenced by infection. Postoperative infections in the groin or axilla offered only local protection from tumor recurrence; the ultimate course of the disease was not affected.

Escherichia coli Infections

Occurrence of nervous-tissue tumors in cattle, horses, cats and dogs.

From 11 North American veterinary university hospitals and clinics, 248 animals were a confirmed diagnosis of nervous-tissue tumor were identified; 7 tumors were found in cattle, 28 in horses, 14 in cats, 199 in dogs, and none in other species. Tumors were divided for analysis into three categories-glial, meningeal, and peripheral nerve. In cattle and horses, all tumors involved peripheral nerves, the risk of which, in horses, reached a plateau at 4-6 years of age and remained constant thereafter. In cats, the tumors were equally distributed among the three tumor categories whereas, in dogs, twice as many glial tumors as meningeal and peripheral nerve tumors were found. The risk for glial tumors in dogs reached a peak at 10-14 years of age, for meningeal at 7-9 years, and for peripheral nerve at 2-3 and 7-9 years. Three canine breeds-English bulldog, boxer, and Boston terrier-had an excessive rish of glial tumors. Except for an excess of skin tumors in dogs with peripheral nerve tumors, there was no unusual occurrence with second primary neoplasms for any species. There was no detectable predisposition by sex for any of the categories of nervous-tissue tumors among any of the four species. The role of genetic abnormalities associated with nervous-tissue tumors and other etiologic factors (e.g., chronic hypoxia) may be clarified by further studies involving canine breeds of "bulldog" ancestry.

Age Factors

Integrating Genomic and Nongenomic Data to Stratify the Risk of Contralateral Breast Cancer After Radiation Therapy.

PURPOSE: Women treated with radiation therapy (RT) for breast cancer have an increased risk of developing radiation-associated contralateral breast cancer (CBC). Predicting CBC events is challenging because of the complex interplay of genomic, treatment, personal, and clinical factors. This study investigated computational methods that integrate genome-wide single-nucleotide polymorphisms and nongenomic data to develop a risk stratification model for developing CBC in women treated with RT for their first primary breast cancer. METHODS AND MATERIALS: This study used a subset of the population-based Women's Environmental Cancer and Radiation Epidemiology study that included 633 CBC cases and 1253 individually matched unilateral breast cancer controls who were treated with RT and had single-nucleotide polymorphism data available from a genome-wide association study. The study population was split into training, validation, and test sets for rigorous modeling and validation. Three data integration methods were compared in terms of their ability to stratify CBC risk: (1) naive integration; (2) sequential integration; and (3) sequential iterative integration. A biological analysis of the final model was performed using gene set enrichment analysis and protein-protein interaction analysis with gene annotation information informed by the model. RESULTS: The best-performing integration method was the sequential iterative integration equipped with the mixed-effect random forest algorithm. This approach achieved an area under the curve of 0.64 to stratify CBC risk in the test set, representing moderate predictive power. Calibration analysis showed good agreement between the lowest and highest risk bins stratified using sorted predicted values in the test set, resulting in an odds ratio of 3.27 for both predicted and observed CBC occurrence. Gene set enrichment analysis and protein-protein interaction analysis revealed that genes with high importance scores were associated with pathways relevant to lipid and fatty acid metabolism as well as breast cancer sensitivity to tamoxifen. CONCLUSIONS: The mixed-effect random forest approach demonstrated the potential for integrating high-dimensional genomic and low-dimensional nongenomic data to stratify CBC risk.

Humans

Long-Term Outcomes of Radiation Monotherapy Versus Combined Radiation Monotherapy + Hormone Therapy in Low-Risk Early-Stage Breast Cancer Patients 70 Years or Older After Breast-Conserving Surgery.

PURPOSE: Standard therapy for breast cancer after breast-conserving surgery is radiation therapy (RT) plus hormone therapy (HT). For patients with a low-risk of recurrence, there is an interest in deescalating therapy. METHODS AND MATERIALS: A retrospective study was carried out for patients treated at the Swedish Cancer Institute from 2000 to 2015, aged 70 years or older, with pT1N0 or pT1NX estrogen receptor-positive and ERBB2-negative unifocal breast cancer without positive surgical margins, high nuclear grade, or lymphovascular invasion. RESULTS: Patient numbers were sufficient to carry out analyses for RT + HT (n = 307) and RT alone (n = 148). The median follow-up was 9.6 years. There were no statistically significant differences in adjusted overall survival (OS), disease-specific death, progression-free survival (PFS), distant recurrence, and second primary cancers with RT monotherapy compared with RT + HT. Cumulative rates of all of these outcomes were <5%, even at 15 years of follow-up, regardless of treatment, greatly outweighed by the incidence of death from other causes in this elderly population. In matched analysis, we calculated a hazard ratio of 1.12 (95% CI, 0.82-1.53) for RT versus RT + HT for OS and a hazard ratio of 1.12 (95% CI, 0.82-1.53) for RT versus RT + HT for PFS. CONCLUSIONS: Our data suggest that elderly, low-risk breast cancer patients have similarly high OS and PFS with low rates of local recurrence, distant recurrence, and death from breast cancer with much higher rates of death from competing causes, whether treated with RT or HT + RT. These patients are likely to die of other causes without disease recurrence, regardless of which of these treatments is used. Thus, they may benefit from the administration of more modern forms of breast irradiation without the need for adjuvant systemic hormone therapy. A detailed analysis of which clinical, pathologic, genomic, and comorbidity variables are needed to select these patients.

Humans

The risk of a second primary cancer in PTEN Hamartoma Tumor Syndrome (PHTS).

PURPOSE: Patients with PTEN Hamartoma Tumor Syndrome (PHTS) have high hereditary cancer risks for breast, endometrial, and thyroid cancer. Patients develop multiple primary cancers, but these risks remain uncertain. We aimed to provide the second primary cancer risk. METHODS: This European cohort study assessed second primary cancer risks with Kaplan-Meier analyses using data from medical files, registries and/or patient questionnaires. RESULTS: Overall, 279 adult PHTS patients with (a history of) cancer were included (80% female). Among females, 106 (54%) developed a PHTS-related second primary cancer after a PHTS-related first primary cancer, whereas 10 (29%) males developed a PHTS-related second primary cancer after a PHTS-related first primary cancer. The 5- and 10-year PHTS-related second primary cancer risks were 24.5% (95% CI = 18.1-32.5) and 45.7% (95% CI = 36.9-55.4) in females and 14.5% (95% CI = 5.7-34.1) and 19.8% (95% CI = 8.6-41.9) in males, respectively. Furthermore, 5- and 10-year risks for a second primary breast cancer after a first primary breast cancer were 23.3% (95% CI = 14.9-35.2) and 45.6% (95% CI = 33.0-60.2) in females, respectively. CONCLUSION: This study demonstrated that PHTS patients have high second primary cancer risks, which is driven by breast cancer in females. Hence, identifying patients with PHTS before or at first primary cancer diagnosis is essential to enable potential early detection or prevention of a second primary cancer through surveillance or risk-reducing surgery.

Humans

Second Primary Malignancies in Patients With B-Cell Lymphomas Treated With Bruton's Tyrosine Kinase Inhibitors: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the overall second primary malignancy (SPM) burden in patients with B-cell lymphomas treated with Bruton's tyrosine kinase (BTK) inhibitors and compare SPM risk versus non-BTK inhibitor or placebo controls. METHODS: We searched major databases from inception to September 30, 2025. The primary outcome was SPM incidence. Consistent treatment backgrounds were defined as comparable baseline clinical and treatment characteristics, with BTK inhibitor exposure as the main between-arm difference. RESULTS: Fifty-two studies involving 9337 patients were included, mainly CLL/SLL; MCL was the largest non-CLL/SLL subtype. Pooled SPM incidence was 8% (95% CI: 6%-11%) with a median follow-up of 31.5&#x2009;months. Multivariable meta-regression identified follow-up duration as the only independent predictor, whereas disease subtype, inhibitor generation, prior therapy lines, study design, and age were not significant. Furthermore, SPM patterns were comparable between CLL/SLL and non-CLL/SLL cohorts. Compared with controls, BTK inhibitors did not significantly increase SPM risk (RR&#x2009;=&#x2009;1.30, 95% CI: 0.95-1.78), a finding confirmed in analyses with consistent treatment backgrounds (RR&#x2009;=&#x2009;1.03, 95% CI: 0.85-1.25). CONCLUSIONS: SPMs occur across disease backgrounds and are mainly influenced by follow-up duration. Current evidence does not establish a direct carcinogenic effect of BTK inhibitors.

Humans

A prediction model for metachronous colorectal cancer: development and validation.

BACKGROUND: Being able to estimate the risk of metachronous disease in a patient with colorectal cancer (CRC) could enable risk-appropriate surveillance. The aim of this study was to develop a risk-prediction model to estimate individual 10-year risk of metachronous disease following a CRC diagnosis. METHODS: A population-based cohort of patients with CRC was recruited soon after diagnosis between 1997 and 2012 from the United States, Canada, and Australia. Cox regression with the least absolute shrinkage and selection operator penalization was used to identify factors that predicted the risk of a new primary CRC diagnosed at least 1 year after the initial CRC diagnosis. Potential predictors included demography, anthropometry, lifestyle factors, comorbidities, personal and family cancer history, medication use, age at diagnosis, and pathological features of the first CRC. Internal validation through bootstrapping was used to evaluate the discrimination and calibration. RESULTS: We included 6085 CRC cases; 138 (2.3%) of these cases were diagnosed with metachronous disease over a median of 12&#x2009;years (IQR&#x2009;=&#x2009;5-17&#x2009;years). Metachronous CRC risk was predicted by body mass index; smoking status; level of physical activity; family history of cancer and synchronous CRC; stage, grade, histological type, and DNA mismatch repair status; and age at diagnosis of the first CRC. The model was valid with a C statistic of 0.65 (95% CI&#x2009;=&#x2009;0.63 to 0.68) and a calibration slope of 0.873 (SD = 0.087). CONCLUSIONS: Metachronous CRC can be predicted with reasonable accuracy using a prediction model that consists of clinical variables collected as part of routine practice.

Humans

Bilateral Conversion Risk in Unilateral Retinoblastoma Using Age and Genetic Testing.

IMPORTANCE: Metachronous bilateral conversion in initially unilateral retinoblastoma is uncommon but clinically consequential, potentially requiring intensified treatment and carrying worse prognosis. Clarifying how age at diagnosis refines genetic-risk stratification could enable safer, more efficient surveillance protocols. OBJECTIVE: To estimate the incidence and timing of metachronous bilateral conversion in unilateral retinoblastoma and assess whether age at diagnosis and RB1 testing are associated with bilateral conversion risk. DESIGN, SETTING AND PARTICIPANTS: This was a retrospective cohort study at a tertiary center in Shanghai, China, including 1108 consecutive children with initially unilateral retinoblastoma diagnosed from July 2010 to October 2024 (after exclusions for short follow-up [n&#x2009;=&#x2009;139], missing data [n&#x2009;=&#x2009;53], or synchronous bilateral disease [n&#x2009;=&#x2009;10]). The median (IQR) follow-up was 43.4 (24.2-67.6) months. EXPOSURES: Age at diagnosis and RB1 genetic status/subtypes assessed by next-generation sequencing and multiplex ligation-dependent probe amplification, including penetrance class (high vs low) and mosaic vs germline categorization. MAIN OUTCOMES AND MEASURES: Time to metachronous bilateral conversion; cumulative incidence functions with death as a competing risk; spatial distribution of fellow-eye tumors. RESULTS: Among 1108 patients (median [IQR] age at diagnosis, 22.2 [12.0-31.4] months; 591 [53.3%] male), 24 (2.2%) developed metachronous bilateral disease. At 24 months, cumulative incidence was 2.2% (95% CI, 1.3-3.1) overall. By genetic status, the 24-month cumulative incidence was 24.8% (95% CI, 13.8-35.9) in RB1 variant-positive vs 1.6% (95% CI, 0.0-3.1) in RB1 variant-negative patients. Among RB1 variant-positive patients, risk clustered among those diagnosed before 9 months, whereas no conversions were observed among those diagnosed at older than 9 months. Four RB1 variant-negative patients who were initially diagnosed at notably late ages (20.9, 42.7, 79.6, and 118 months) subsequently converted; these cases likely represent undetected low-level mosaicism, somatic variants below detection thresholds, or rare genomic events not captured by standard sequencing panels. Fellow-eye tumors did not involve macula and showed a nasal-predominant distribution. CONCLUSIONS AND RELEVANCE: The findings in this study suggest that age at diagnosis may refine genetic risk stratification for metachronous bilateral conversion. RB1 variant-positive patients diagnosed at 9 months or later represent a very low-risk subgroup that may warrant surveillance deescalation, while rare late conversions in RB1 variant-negative patients necessitate continued long-term monitoring.

Humans

Non-Hodgkin's lymphoma and acute myeloblastic leukemia: a report of 12 cases and review of the literature.

Twelve cases of non-Hodgkin's lymphoma and acute myeloblastic leukemia or one of its variants are reported. An additional 33 cases from the literature are reviewed. The mean interval between the diagnosis of lymphoma and acute leukemia is 5.2 years. In 5 patients the two diseases occurred simultaneously or within 6 months of each other. All but 10 of the 45 patients received radiation therapy for their lymphoma. Nine patients had either total nodal or total body irradiation or both. Eight patients received chemotherapy alone. No patient was untreated. Survival after the diagnosis of acute leukemia ranged from 3 days to 14 months, with a median of 3 months. Four patients achieved complete hematological remission following antileukemic therapy. Acute leukemia is estimated to occur in patients with non-Hodgkin's lymphoma in New York State with a 37-fold increased frequency over the expected number. Although acute leukemia may occur in a higher than expected frequency in patients with non-Hodgkin's lymphoma because of an increased risk of a second neoplasm in patients with a primary tumor, it seems more likely that the acute leukemia may be related to the radiotherapy and/or chemotherapy administered to treat the lymphoma. Late death from leukemia after chemotherapeutic or radiotherapeutic remission of advanced non-Hodgkin's lymphoma is preferable to morbidity and/or early death from untreated or inadequately treated lymphoma.

Adolescent

Problems in management of primary bilateral germ cell testicular tumors: report of 3 cases and review of literature.

Bilateral primary germ cell tumors are uncommon but not rare in men with primary testicular tumors. In our series of 78 cases of germ cell tumors 3 (3.8 per cent) were bilateral. In the management of a second neoplasm the same general principles apply as those for the first tumor but one must be aware of the potential complications of radiotion therapy when the total dose for cure of the first and second neoplasms exceeds the tolerance dose of normal tissue and therapy must be modified accordingly. Prognosis is not necessarily poor when a second primary tumor develops and complications can be reduced to a low level with appropriate therapy. Our outline for therapy is presented.

Adult

Histiocytic lymphoma of the ileocecal region after chemotherapy for multiple myeloma.

Histiocytic lymphoma of the ileocecal region developed in a patient with multiple myeloma following successful long-term alkylating agent therapy. Five and one-half years after the diagnosis of myeloma, while in remission on cyclophosphamide therapy, the patient experienced severe abdominal right lower quadrant pain due to a large cecal lymphoma. A right hemicolectomy was performed with relief of symptoms. However, 9 months later, while still asymptomatic, routine physical examination revealed a recurrent right lower quadrant tumor. Radiation therapy decreased the size of the mass, but five months later partial small bowel obstruction occurred because of recurrent lymphomatous infiltration. The patient died 7 years after the diagnosis of myeloma with extensive abdominal lymphoma. There was no evidence of recurrent myeloma after the initial remission on cyclophosphamide therapy. This patient adds to the growing literature of a second malignancy occurring after prolonged successful chemotherapy of a primary neoplasm.

Cecal Neoplasms

A clinico-pathological study on the correlation of immunosuppression and multiple primary malignant neoplasmas.

At present it is obvious that the incidence of second malignancies in patients with malignant diseases increases after prolonged treatment with immunosuppressive, or antineoplastic agents. The occurrence of such additional malignant diseases was analysed in our five-years autopsy material. During this period 7670 autopsies were performed. Malignant diseases were observed in 1707 cases (22.1%) and among them in 58 cases were proved multiple primary malignant neoplasms (3.3%). The average time between the occurrence of initial and second tumors was 29 months. The frequency of second tumors in patients with leukemias (mainly chronic lymphocytic leukemia) were four times higher than in patients with tumors of epithelial origin. Hepatocarcinomas arose in cirrhotic livers and astrocytomas were often followed by new malignancies. In consequence of successfully applied surgical, radiological and combined immunosuppressive, antineoplastic therapy the survival of cancer patients lengthened, so among different side-effects of the used therapy the oncogenesis cannot be left out of account. The danger of subsequent malignant tumors makes it imperative that immunosuppression should only be applied when strictly indicated.

Adult

Adenocarcinoma of the lung in non-Hodgkin's lymphoma.

The development of a second neoplasm is a rare complication in patients with various types of primary malignancy. This report describes two patients with non-Hodgkin's lymphoma who developed adenocarcinoma of the lung and malignant pleural effusion following many years of cytotoxic therapy. The value of cytological examination of the sputum and pleural aspirate, as well as fibreoptic bronchial biopsy in the diagnosis are emphasised. The higher incidence of this complication in patients with lymphocytic type of non-Hodgkin's lymphoma may be due to their longer survival and probable basic immune defects which become overt after chemotherapy.

Adenocarcinoma