Malignancies In Cancer Survivors Research Articles

148P Breast cancer as second primary malignancy in cancer survivors: Experience from a Tertiary Cancer Center in India

Improvement in cancer detection and advances in treatment have resulted in an increasing number of cancer survivors. They are at risk of sequelae such as second primary malignancy (SPM) which can be due to variety of factors like genetic, environmental and pervious treatment. Being one of the most common malignancies detected in females worldwide, breast cancer presenting as SPM is increasingly reported. The patients treated in the breast cancer clinic, Department of Medical Oncology at Regional Cancer Center, a leading tertiary cancer center in South India were studied during the period January 2017 to December 2019. Among 3500 patients, 25 presented as SPM. Details of the patients were noted from the case records. Those patients with prior histologically proven breast cancer were excluded. Among the 25 patients, 24 were females and one was male. The most common primary malignancy was carcinoma thyroid (5 cases) followed by osteosarcoma and carcinoma endometrium (3 cases each).The median time interval between primary and second malignancy was 9 years (range 2-26 years). The median age at diagnosis of second malignancy was 59 years (range 39-79 years) and 76% of the patients were more than 50 years of age. Most of the patients presented with early stage disese (19 were stage 1 or 2), 6 were stage 3 and none was metastatic at presentation (9 triple negative, 9 hormone receptor+ and 7 HER2+). All patients received curative treatment based on the stage and tumor biology. In those who had received anthracyclin agents as part of their initial treatment, the same was avoided in the management of SPM. All of the HER2 positive patients received anti HER2 agents and hormone positive patients received endocrine agents based on the menopausal status. Patients who were on targeted agents were allowed to continue the same with adequate monitoring. In patients who had received radiation previously, reirradiation was given with the dose adjustments. Among the 25 patients, two progressed after initial treatment and further follow up is needed to to comment on the survival. The possibility of SPM must always be considered in the follow-up visit of cancer survivors. Tailoring of treatment may be required based on the previous therapy.

Second Malignancies after Radiation Therapy: Update on Pathogenesis and Cross-sectional Imaging Findings

A wide spectrum of second cancers occur as late complications of radiation therapy (RT) used to treat various malignancies. In addition to the type and dose of radiation, lifestyle, environmental, and genetic factors are important to the development of second malignancies in cancer survivors. Typically, RT-induced malignancies (RTIMs) are biologically aggressive cancers with a variable period of 5-10 years for hematologic malignancies and 10-60 years for solid tumors between RT and the development of the second cancer. Although carcinomas and leukemias commonly develop after low-dose RT, sarcomas occur in tissues or organs that receive high-dose RT. Angiosarcomas and unclassified pleomorphic sarcomas are the two most common RT-associated sarcomas; other sarcomas include malignant peripheral nerve sheath tumors, leiomyosarcomas, osteosarcomas, chondrosarcomas, and dedifferentiated or pleomorphic liposarcomas. Select RTIMs show tumor genetic characteristics that allow accurate diagnosis. Nearly all cutaneous angiosarcomas after RT for breast cancer and 90% of RT-associated malignant peripheral nerve sheath tumors are characterized by MYC gene amplifications and loss of H3 K27me3 expression, respectively. Classic papillary thyroid carcinomas that develop after RT frequently harbor RET/PTC rearrangements and have a favorable prognosis, despite their advanced stage at patient presentation. Select RTIMs demonstrate characteristic imaging findings and typically develop in the prior radiation field. Imaging is essential to early diagnosis, characterization, localization, and staging of RTIMs. Familiarity of radiologists with the diverse spectrum of RTIMs is essential for early diagnosis and optimal management. An invited commentary by Shapiro is available online. ©RSNA, 2021.

Review of risk factors of secondary cancers among cancer survivors.

Improvements in cancer survival have made the long-term risks from treatments more important, in particular among the children, adolescents and young adults who are more at risk particularly due to a longer life expectancy and a higher sensitivity to treatments. Subsequent malignancies in cancer survivors now constitute 15 to 20% of all cancer diagnoses in the cancer registries. Lots of studies are published to determine risk factors, with some controversial findings. Just data from large cohorts with detailed information on individual treatments and verification of what is called "secondary cancers" can add some knowledge, because their main difficulty is that the number of events for most second cancer sites are low, which impact the statistical results. In this review of the literature, we distinguish second and secondary cancers and discuss the factors contributing to this increased risk of secondary cancers. The article concludes with a summary of current surveillance and screening recommendations.

Data on the DNA damaging and mutagenic potential of the BH3-mimetics ABT-263/Navitoclax and TW-37.

Unfortunately, the mutagenic activities of chemotherapy and radiotherapy can provoke development of therapy-induced malignancies in cancer survivors. Non-mutagenic anti-cancer therapies may be less likely to trigger subsequent malignant neoplasms. Here we present data regarding the DNA damaging and mutagenic potential of two drugs that antagonize proteins within the Bcl-2 family: ABT-263/Navitoclax and TW-37. Our data reveal that concentrations of these agents that stimulated Bax/Bak-dependent signaling provoked little DNA damage and failed to trigger mutations in surviving cells. The data supplied in this article is related to the research work entitled "Inhibition of Bcl-2 or IAP proteins does not provoke mutations in surviving cells" [1].

A retrospective and prospective study of double malignancies in a tertiary care hospital in south India - a ten years' experience

Background: The occurrence of second malignancies in cancer survivors is not uncommon. Due to advances in diagnostic and therapeutic modalities, the survival of cancer patients has improved and the incidence of second malignancies is also on the rise. The second malignancy may be synchronous or metachronous. Though there are plenty of case reports on double malignancies, original studies are less. The present study aims to analyse the frequency, types of double malignancies and their effect on the morbidity and mortality of the patients. Methods: This is a retrospective and prospective analysis of cancer patients done in a tertiary care hospital. All patients who presented with double malignancies from January 2004 to December 2014 were included. Retrospective data was obtained for cases from January 2004 to October 2011 and prospective data was obtained from November 2011 to December 2014. The study included 32 patients with double malignancies. Results: Gynaecological malignancies were most common in our study, followed by head and neck and gastrointestinal malignancies. Most of the malignancies were synchronous (56.25%). Double malignancies involving the head and neck, female reproductive tract, breast can be explained by common etiological factors like Human papillomma virus (HPV). Field cancerisation explains the synchronous cancers in Head and neck, upper aero digestive tract and reproductive tract. Conclusions: This study emphasises the importance of screening cancer patients for other primary malignancies during initial evaluation as well as during follow up period, in addition to the metastatic workup. It also stresses that timely reduction of risk factors in cancer survivors can prevent further malignancies.

Second primary malignancies in cancer survivors: epidemiology, role of anticancer therapy

The recent years have seen considerable advancement in the therapy of oncology patients and hence better survival and longer lifespan. Thus, studies on the distant effects of antitumor therapy have become increasingly important. That particularly concerns the risk of development of the second primary tumors. The patients that received therapy for the first malignant neoplasm become a higher-risk group for the development of a second tumor for their entire subsequent life. The review represents the data of analytical epidemiological studies on the second leukemia and solid tumors caused by the aftereffects of antitumor therapy using alkylating agents. Data are also considered on the risk of the second tumors that developed upon transplantation of stem cells. The second tumor etiology includes other significant risk factors such as genetic predisposition, smoking, alcohol consumption, imbalanced diet, etc. In combination with the aftereffects of antitumor therapy they may influence significantly the probability of the development of the second tumors in cancer patients, which should be considered in developing preventive measures. The review data suggest the need for cooperation of specialists in various fields and the use of clinical, epidemiological and molecular approaches to study the carcinogenesis of the first and second tumors, the choice of efficient and the safest methods of antitumor therapy to reduce the risk of the development of distant aftereffects and their prevention.

DNA Repair Gene Polymorphisms and Their Relation With DNA Damage, DNA Repair, and Total Antioxidant Capacity in Childhood Acute Lymphoblastic Leukemia Survivors

Oxidative stress and defective DNA repair are major contributory factors in the initiation and progression of carcinogenesis. Chemotherapy and radiotherapy cause oxidative DNA damage, consume antioxidant capacity, and impair DNA repair activity. These effects of chemotherapy and radiotherapy may be contributory factors in the development of secondary malignancy in cancer survivors. Basal, H2O2-induced, and postrepair DNA damage; urinary 8-hydroxydeoxyguanosine level as a marker of oxidatively damaged DNA; and serum total antioxidant capacity were measured; XPD Lys751Gln, XRCC1 Arg399Gln, and XRCC1 Arg194Trp polymorphisms were analyzed in childhood acute lymphoblastic leukemia (ALL) survivors. Basal and H2O2-induced DNA damage were found to be higher in the ALL survivor group versus the control group, however, there was no significant difference between the other parameters. No association was found between the examined parameters and polymorphisms of XPD 751 and XRCC1 399 and both the groups. XRCC1 194Trp allele was found to be associated with a low level of postrepair DNA damage in the ALL survivors. In conclusion, basal DNA damage and susceptibility to oxidation are high in childhood ALL survivors. This situation which may easily lead to occurrence of a secondary cancer does not seem to be a result of deficient DNA repair.

Unexpected Second Primary Malignancies Detected by F-18 FDG PET/CT During Follow-up for Primary Malignancy: Two Case Reports.

As the survival rate of cancer patients has increased over the last few decades, the risk of cancer survivors developing second primary malignancies has gained attention. We report two rare cases of second primary hematologic malignancy detected by (18)F-fluorodeoxyglucose (F-18 FDG) positron emission tomography/computed tomography (PET/CT) during follow-up for primary solid malignancies. Acute lymphoblastic leukemia developed in a breast cancer patient and non-Hodgkin lymphoma in an anal cancer patient. F-18 FDG PET/CT findings led to the diagnosis of unexpected second primary hematologic malignancy in cancer survivors in these two cases.