Search

Abstract Since the United States Food and Drug Administration (FDA) approved the first chimeric antigen receptor T-cell (CAR-T) therapy in 2017, it has marked a major breakthrough in cancer treatment, leading to a surge in global research and applications in this field. In recent years, China has made rapid progress, quickly catching up through heavy investment in CAR-T construction, preparation processes, and treatment strategies. China’s CAR-T therapy market is driven by substantial pharmaceutical investment targeting its vast population, yet high therapy costs remain uncovered by basic medical insurance. In November 2023, FDA issued a warning about the risk of secondary cancers in patients undergoing CAR-T therapy, sparking global concern. In fact, the China National Medical Products Administration (NMPA) preemptively implemented a series of measures to address the safety concerns of CAR-T therapy, emphasizing the risk of secondary cancers and advising lifelong monitoring as part of the approval process for CAR-T products. Nevertheless, additional regulatory measures are needed to address emerging risks, particularly the threat of secondary cancers. The authors believe that raising the standards for Investigational New Drug (IND) approval and establishing a dynamic reporting and feedback system based on real-world data will strengthen regulatory oversight and support the sustainable growth of the CAR-T industry in China.

Since the United States Food and Drug Administration (FDA) approved the first chimeric antigen receptor T-cell (CAR-T) therapy in 2017, it has marked a major breakthrough in cancer treatment, leading to a surge in global research and applications in this field. In recent years, China has made rapid progress, quickly catching up through heavy investment in CAR-T construction, preparation processes, and treatment strategies. China's CAR-T therapy market is driven by substantial pharmaceutical investment targeting its vast population, yet high therapy costs remain uncovered by basic medical insurance. In November 2023, FDA issued a warning about the risk of secondary cancers in patients undergoing CAR-T therapy, sparking global concern. In fact, the China National Medical Products Administration (NMPA) preemptively implemented a series of measures to address the safety concerns of CAR-T therapy, emphasizing the risk of secondary cancers and advising lifelong monitoring as part of the approval process for CAR-T products. Nevertheless, additional regulatory measures are needed to address emerging risks, particularly the threat of secondary cancers. The authors believe that raising the standards for Investigational New Drug (IND) approval and establishing a dynamic reporting and feedback system based on real-world data will strengthen regulatory oversight and support the sustainable growth of the CAR-T industry in China. [ABSTRACT FROM AUTHOR]

Simple Summary: Juvenile nasopharyngeal angiofibroma (JNA) presents a therapeutic challenge in its advanced stages due to the close proximity to critical structures at the skull base. While radiotherapy is an effective treatment alternative, radiation-induced complications due to dose deposition in healthy tissue remain a major concern. Particle radiotherapy offers a high degree of conformality, and notably, helium ions present a promising treatment option due to their favorable biophysical characteristics between protons and carbon ions, supporting their reconsideration for clinical application. We retrospectively designed helium ion therapy (HRT) plans for all patients previously treated with proton therapy (PRT) at the Heidelberg Ion-Beam Therapy Center. Our findings indicate potential dosimetric advantages of HRT over PRT for advanced JNA, suggesting enhanced target coverage along with reduced dose deposition in healthy tissue, thereby potentially mitigating acute and late-term complications, including secondary neoplasms. This is particularly important given the benign nature of JNA and the patients' young age. Helium ion therapy (HRT) is a promising modality for the treatment of pediatric tumors and those located close to critical structures due to the favorable biophysical properties of helium ions. This in silico study aimed to explore the potential benefits of HRT in advanced juvenile nasopharyngeal angiofibroma (JNA) compared to proton therapy (PRT). We assessed 11 consecutive patients previously treated with PRT for JNA in a definitive or postoperative setting with a relative biological effectiveness (RBE) weighted dose of 45 Gy (RBE) in 25 fractions at the Heidelberg Ion-Beam Therapy Center. HRT plans were designed retrospectively for dosimetric comparisons and risk assessments of radiation-induced complications. HRT led to enhanced target coverage in all patients, along with sparing of critical organs at risk, including a reduction in the brain integral dose by approximately 27%. In terms of estimated risks of radiation-induced complications, HRT led to a reduction in ocular toxicity, cataract development, xerostomia, tinnitus, alopecia and delayed recall. Similarly, HRT led to reduced estimated risks of radiation-induced secondary neoplasms, with a mean excess absolute risk reduction of approximately 30% for secondary CNS malignancies. HRT is a promising modality for advanced JNA, with the potential for enhanced sparing of healthy tissue and thus reduced radiation-induced acute and long-term complications. [ABSTRACT FROM AUTHOR]

The risks of secondary cancers associated with human papillomavirus (HPV) infection are as much as three times higher for survivors of pediatric, adolescent, and young adult cancer (PYAC) compared to the general population. Despite this, HPV vaccination rates among PYAC survivors remain low. Whereas pediatric oncology providers endorse HPV vaccination of PYAC survivors, many lack the resources or opportunities to intervene. The responsibility of HPV vaccination, therefore, falls to primary care providers and practices. This article provides an overview of the challenges with HPV vaccination that are distinct to PYAC survivors and discusses potential strategies to increase HPV vaccine coverage in this population. [ABSTRACT FROM AUTHOR]

Simple Summary: Advanced juvenile nasopharyngeal angiofibroma (JNA) can present a considerable therapeutic challenge. Photon radiotherapy has been recognized as an effective treatment approach for recurrent or inoperable advanced JNA in an additive or definitive setting. However, due to the benign nature of JNA and the young age of the affected patients, concerns about long-term radiation-induced morbidity have led to a certain hesitance towards this treatment modality. Proton therapy (PRT) presents a promising alternative for treating benign conditions in young patients, yet there remains a gap in the literature regarding its application to JNA. We retrospectively examined the outcomes of patients with JNA who underwent PRT in our center and evaluated the dosimetric advantages of PRT over conformal radiotherapy. This study is the first report investigating PRT for advanced JNA, highlighting PRT's safety and effectiveness as a viable therapeutic option. Dosimetric and complication risk evaluations suggest that PRT holds the potential to reduce long-term radiation-induced complications, including the development of secondary neoplasms or decline in neurocognitive function. Purpose: To provide the first report on proton radiotherapy (PRT) in the management of advanced nasopharyngeal angiofibroma (JNA) and evaluate potential benefits compared to conformal photon therapy (XRT). Methods: We retrospectively reviewed 10 consecutive patients undergoing PRT for advanced JNA in a definitive or postoperative setting with a relative biological effectiveness weighted dose of 45 Gy in 25 fractions between 2012 and 2022 at the Heidelberg Ion Beam Therapy Center. Furthermore, dosimetric comparisons and risk estimations for short- and long-term radiation-induced complications between PRT plans and helical XRT plans were conducted. Results: PRT was well tolerated, with only low-grade acute toxicities (CTCAE I–II) being reported. The local control rate was 100% after a median follow-up of 27.0 (interquartile range 13.3–58.0) months. PRT resulted in considerable tumor shrinkage, leading to complete remission in five patients and bearing the potential to provide partial or complete symptom relief. Favorable dosimetric outcomes in critical brain substructures by the use of PRT translated into reduced estimated risks for neurocognitive impairment and radiation-induced CNS malignancies compared to XRT. Conclusions: PRT is an effective treatment option for advanced JNA with minimal acute morbidity and the potential for reduced radiation-induced long-term complications. [ABSTRACT FROM AUTHOR]

Background: Breast cancer (BC) is one of the most common cancers worldwide. In recent years, numerous non‑chemotherapy agents have been developed for BC treatment, including targeted agents, new hormonal therapies, and immunotherapies. However, despite the widespread use of these agents, chemotherapies are still an important cornerstone in BC treatment. Similarly, serious de‑escalation studies in radiotherapy use have been conducted in recent years. These two treatment modalities, which we frequently use in the treatment of BC due to their effectiveness, may also have serious side effects. Case Presentation: In this article, I will present a case of multiple myeloma (MM) and myxofibrosarcoma (MFS) that occurred many years later in a patient who completed adjuvant chemotherapy and radiotherapy for BC. MM has developed due to previous chemotherapy and MFS has developed due to previous radiotherapy. Conclusion: We usually treat our cancer patients with chemotherapy or radiotherapy to prolong their lives. In addition to the benefits we provide, may negatively affect the lifetime and quality of life by causing the development of metachronous secondary cancers in some patients. In this case report, I will present the “ironic” side of oncology science and treatment. [ABSTRACT FROM AUTHOR]

• This study investigates the effectiveness of novel nanocomposite shielding materials in reducing out-of-field radiation doses during radiation therapy. • The research employs detailed simulations of a clinical linear accelerator and a mesh-type human phantom to estimate out-of-field organ doses. • Results demonstrated that nanocomposites made of PTFE with PtO 2 , IrO 2 , and Bi 2 O 3 nanoparticles significantly reduce radiation exposure to non-target tissues. This study investigates the effectiveness of novel nanocomposite shielding materials in reducing out-of-field radiation doses during radiation therapy, employing Geant4 Monte Carlo (MC) simulations alongside an anthropomorphic female phantom. The research focuses on two radiation modalities: 6 MV beams with and without flattening filters. Utilizing the Geant4 MC code, detailed simulations of a Varian Clinac 2100C/D linear accelerator and an ICRP-145 mesh-type human phantom were conducted to estimate the doses to out-of-field organs from unintended secondary radiation. This involved simulating a comprehensive linac model, including all relevant beam-line components, and assessing the shielding effects of three different nanocomposites doped with metal nanoparticles at various thicknesses. The nanocomposites, comprising Polytetrafluoroethylene (PTFE), with PtO 2 , IrO 2 , and Bi 2 O 3 nanoparticles, were evaluated for their potential to reduce patient organ doses from stray photon doses. The results showed that these materials could significantly lower radiation exposure to non-target tissues. [ABSTRACT FROM AUTHOR]

The risks of secondary cancers associated with human papillomavirus (HPV) infection are as much as three times higher for survivors of pediatric, adolescent, and young adult cancer (PYAC) compared to the general population. Despite this, HPV vaccination rates among PYAC survivors remain low. Whereas pediatric oncology providers endorse HPV vaccination of PYAC survivors, many lack the resources or opportunities to intervene. The responsibility of HPV vaccination, therefore, falls to primary care providers and practices. This article provides an overview of the challenges with HPV vaccination that are distinct to PYAC survivors and discusses potential strategies to increase HPV vaccine coverage in this population.

Abstract Purpose We explored the potential overall survival (OS) benefit of bleomycin, etoposide, doxorubicin (Adriamycin), cyclophosphamide, vincristine (Oncovin), procarbazine, and prednisone (BEACOPP) over doxorubicin (Adriamycin), bleomycin, vinblastine, and dacarbazine (ABVD) in a pooled analysis of four randomized trials. Patients and methods Primary objective was to evaluate the OS impact of BEACOPP using individual patient data. Secondary objectives were progression‐free survival (PFS), secondary cancers, and use of autologous stem cell transplantation (ASCT). Results About 1227 patients were included. The 7‐year OS was 84.3% (95% CI 80.8‐87.2) for ABVD vs 87.7% (95% CI 84.5‐90.2) for BEACOPP. Two follow‐up periods were identified based on survival curves and hazard ratio (HR) over time. For the first 18 months, there was no difference. For the second period of ≥18 months, ABVD patients had a higher death risk (HRABVD vs BEACOPP = 1.59; 95% CI 1.09‐2.33). A Cox model stratified by trial and evaluating the effect of treatment and International Prognostic Index (IPI) score as fixed effects showed that both were statistically significant (treatment, P = .0185; IPI score, P = .0107). The 7‐year PFS was 71.1% (95% CI 67.1‐74.6) for ABVD vs 81.1% (95% CI 77.5‐84.2) for BEACOPP (P

The use of radiation therapy is a cornerstone of modern cancer treatment. The number of patients that undergo radiation as a part of their therapy regimen is only increasing every year, but this does not come without cost. As this number increases, so too does the incidence of secondary, radiation-induced neoplasias, creating a need for therapeutic agents targeted specifically towards incidence reduction and treatment of these cancers. Development and efficacy testing of these agents requires not only extensive in vitro testing but also a set of reliable animal models to accurately recreate the complex situations of radiation-induced carcinogenesis. As radiation-induced leukemic progression often involves genomic changes such as rearrangements, deletions, and changes in methylation, the laboratory mouse Mus musculus, with its fully sequenced genome, is a powerful tool in cancer research. This fact, combined with the molecular and physiological similarities it shares with man and its small size and high rate of breeding in captivity, makes it the most relevant model to use in radiation-induced leukemia research. In this work, we review relevant M. musculus inbred and F1 hybrid animal models, as well as methods of induction of radiation-induced myeloid leukemia. Associated molecular pathologies are also included.

Purpose: We explored the potential overall survival (OS) benefit of bleomycin, etoposide, doxorubicin (Adriamycin), cyclophosphamide, vincristine (Oncovin), procarbazine, and prednisone (BEACOPP) over doxorubicin (Adriamycin), bleomycin, vinblastine, and dacarbazine (ABVD) in a pooled analysis of four randomized trials. Patients and methods: Primary objective was to evaluate the OS impact of BEACOPP using individual patient data. Secondary objectives were progression‐free survival (PFS), secondary cancers, and use of autologous stem cell transplantation (ASCT). Results: About 1227 patients were included. The 7‐year OS was 84.3% (95% CI 80.8‐87.2) for ABVD vs 87.7% (95% CI 84.5‐90.2) for BEACOPP. Two follow‐up periods were identified based on survival curves and hazard ratio (HR) over time. For the first 18 months, there was no difference. For the second period of ≥18 months, ABVD patients had a higher death risk (HRABVD vs BEACOPP = 1.59; 95% CI 1.09‐2.33). A Cox model stratified by trial and evaluating the effect of treatment and International Prognostic Index (IPI) score as fixed effects showed that both were statistically significant (treatment, P =.0185; IPI score, P =.0107). The 7‐year PFS was 71.1% (95% CI 67.1‐74.6) for ABVD vs 81.1% (95% CI 77.5‐84.2) for BEACOPP (P <.001). After ABVD, 25 secondary cancers (4.0%) were reported with no myelodysplasia (MDS)/acute myeloid leukemia (AML) compared to 36 (6.5%) after BEACOPP, which included 13 patients with MDS/AML. Following ABVD, 86 patients (13.8%) received ASCT vs 39 (6.4%) for BEACOPP. Conclusions: This analysis showed a slight improvement in OS for BEACOPP and confirmed a PFS benefit. Frontline use of BEACOPP instead of ABVD increased secondary leukemia incidence but halved the requirement for ASCT. [ABSTRACT FROM AUTHOR]

Childhood cancer survivors (CCSs) are at an increased risk for secondary cancers, including colorectal, thyroid, lung, and breast. Treatment with abdominal radiotherapy and/or alkylating agent chemotherapy has been associated with an increased risk for colorectal adenomas and colorectal cancer (CRC) in CCSs. The phenotype of therapy-associated polyposis (TAP) is not well-understood, given the paucity of cases described in the literature. Further defining the phenotype of TAP is important to increase the primary care provider's awareness of when to begin CRC screening in these patients. We present a case of a patient with possible acquired polyposis that seems to meet the criteria identified in the literature for TAP. The purpose of this case study is to add to the body of knowledge related to TAP, further defining the phenotype. Better understanding of therapy-related risks in CCSs and hereditary predisposition will provide primary care providers and their patients with an improved plan for CRC screening. [ABSTRACT FROM AUTHOR]

The Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) held the 13th edition of the Clinical Practices Harmonization Workshops. Our workgroup reviewed the current data on the incidence, screening methods and international guidelines for the prevention of secondary solid cancers following allogeneic hematopoietic stem cell transplantation. The purpose of this workshop was to provide recommendations for the screening and prevention of secondary malignancies to Francophone transplantation centers., (Copyright © 2023 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Chemo- and radiotherapy are treatments very helpful to cure cancers but are also well known for adverse effects such as secondary cancers. Breast cancers following Hodgkin lymphoma have been relatively well studied. Breast cancers after radiotherapy covering or nearby breasts or nipples are usually carcinomas or secondary sarcomas. Among the big cohort of patients treated for breast carcinomas, breast lymphomas developed in the same area are not usual. Nevertheless, published studies described a significant increased risk of non-Hodgkin lymphoma after initial radiotherapy for a solid cancer. Here, we report a case of a secondary breast lymphoma observed in a 53-year-old woman treated 13 years before for a ductal carcinoma and analyse such second tumors with a review of the literature. This case report emphasizes the importance of the biopsy in case of recurrence in breast cancer to give the appropriate treatment. [ABSTRACT FROM AUTHOR]

Introduction: The treatment with tyrosine kinase inhibitors (TKIs) has drastically improved the outcome of chronic myeloid leukemia (CML) patients. This study was conducted to examine the risk of secondary cancers (SCs) in the CML patients who were diagnosed and treated in the TKI era in the United States. Methods: The surveillance epidemiology and end results (SEER) database was used to identify CML patients who were diagnosed and received treatment during January 2002-December 2014. Standardized incidence ratios (SIRs) and absolute excess risks (AER) were calculated. Results: Overall, 511 SCs (excluding acute leukemia) developed in 9,200 CML patients followed for 38,433 person-years. The risk of developing SCs in the CML patients was 30% higher than the age, sex and race matched standard population (SIR 1.30, 95% CI: 1.2-1.40; p < 0.001). The SIRs for CLL (SIR 3.4, 95% CI: 2-5.5; p < 0.001), thyroid (SIR 2.2, 95% CI: 1.2-3.5; p < 0.001), small intestine (SIR 3.1, 95% CI: 1.1-7; p = 0.004), gingiva (SIR 3.7, 95% CI: 1.2-8.7; p = 0.002), stomach (SIR 2.1, 95% CI: 1.1-3.5; p = 0.005), lung (SIR 1.4, 95% CI: 1.1-1.7; p = 0.006) and prostate (SIR 1.3, 95% CI: 1.02-1.6; p = 0.026) cancer among CML patients were significantly higher than the general population. The risk of SCs was higher irrespective of age and it was highest in the period 2-12 months after the diagnosis of CML. The risk of SCs in women was similar to that of the general population. Conclusion: CML patients diagnosed and treated in the TKI era in the United States are at an increased risk of developing a second malignancy. The increased risk of SCs in the early period after CML diagnosis suggests that the risk of SCs may be increased due to the factors other than TKIs treatment. [ABSTRACT FROM AUTHOR]

Purpose: In the U.S., Kaposi sarcoma (KS) occurs mostly in HIV-infected patients, who are also at increased risk of developing secondary cancers. The trends in secondary cancer risk are unclear in the HAART era.Methods: We extracted data from the SEER database on patients diagnosed with KS between 1981 and 2013, stratified into the pre-HAART (1981-1995) and HAART (1996-2013) eras. We compared the risk of secondary cancer in KS patients and the general population, and estimated the absolute risk.Results: We followed 13,535 KS patients for 49,813 person-years, during which 1,041 secondary cancers were diagnosed: 774 in the pre-HAART and 267 in the HAART era. In the pre-HAART era, non-Hodgkin's lymphoma (NHL) and anal carcinomas were the most common secondary cancers. The standard incidence ratio of secondary cancers decreased from 3.44 (pre-HAART era) to 1.94 (HAART era) in patients aged <70 years. The absolute excess risk decreased from 178 to 68 cases per 10,000 person-years. The risk of NHL decreased, while the risk of anal carcinoma did not change significantly. The risk of lung cancer was lower in KS patients than in the general population. The absolute risk of non-AIDS-defining cancers increased fourfold in the HAART era.Conclusions: The absolute risk of non-AIDS-defining secondary cancers has increased in KS patients in the HAART era. However, the overall relative risk of secondary cancers has decreased, mainly due to a significant decrease in the risk of NHL. [ABSTRACT FROM AUTHOR]

Introduction: There is a growing interest in the study of radiation-induced secondary cancer. The aim of this work is (i) to estimate the peripheral doses attributable to intensity modulated radiotherapy (IMRT) and mega-voltage cone beam computed tomography (MV-CBCT) for some organs at risk (OARs) which surround the target being treated (Nasopharynx) in paediatric patients. (ii) To estimate the risk of radiation-induced secondary cancers attributable to patient setup verification imaging dose using MV-CBCT for Nasopharyngeal Carcinoma (NPC) in paediatric patients and comparing it with that attributable to the therapeutic dose using IMRT.Methods: Intensity modulated radiotherapy treatment planning of 10 NPC paediatric patients was carried out on KonRad release 2.2.23. The additional radiation doses to the patients attributable to MV-CBCT were calculated also using Xio Version 4.4. A paediatric phantom and thermoluminescent dosimeters (TLDs) were used to measure the patient doses attributable to IMRT. These doses were then compared with the calculated doses. The risk of induced secondary cancers attributable to IMRT and MV-CBCT was calculated and compared to each other.Results: The absorbed doses (mean dose) for the OARs (Brain, Brain stem, spinal cord, thyroid, oesophagus, mandible, heart, optic nerve, lung and eye) were higher for the therapeutic dose than for the imaging dose used in the verification of patient position before and during the treatment. The risk of induced secondary cancers in thyroid, oesophagus and lung (the only organs from the OARs which have tabulated values for risk calculations) was higher for therapeutic dose (7.29 ± 0.73%, 2.62 ± 0.17% and 6.76 ± 0.87%, respectively) than for verification imaging dose (0.14 ± 0.00%, 0.06 ± 0.00%, 0.10 ± 0.03% respectively).Conclusion: The risk of secondary cancers attributable to verification imaging dose using MV-CBCT is very small compared to therapeutic dose using IMRT. Therefore, it is important to focus on the risk of secondary cancers attributable to therapeutic dose especially when using IMRT, where the produced leakage radiation is considerably high compared to some other techniques (such as conformal radiotherapy). [ABSTRACT FROM AUTHOR]

Background Major infections (MIs), secondary cancers (SCs) and autoimmune diseases (ADs) are the most common and relevant complications in patients with chronic lymphocytic leukaemia. Methods We performed a single-centre retrospective study to investigate the prevalence of the above quoted complications, the association with most important prognostic markers and their impact on survival (n = 795). Results Almost one out of three patients experienced at least one complication and only 0.9% of the cohort developed all three complications. One hundred and twenty (20%) subjects developed SC, 98 MI (12%) and 80 AD (10%); these complications seem to occur in a mutually exclusive manner. By Kaplan–Meier analysis we estimated that after 20 years from the diagnosis SC, MI and AD occurred in 48%, 42% and 29% of patients, respectively. Furthermore, we showed that some clinical and biological markers are skewed among patients with different complications and that subjects with MI and SC had a worse prognosis than those with AD and all other patients (p < 0.0001). Conclusions This study reveals the existence of different clinical subsets of chronic lymphocytic leukaemia patients characterised by an increased and different risk for developing specifically MI, SC and AD. [ABSTRACT FROM AUTHOR]

Radiation delivery to cancer patients for radiotherapy is invariably accompanied by unwanted radiation to other parts of the patient′s body. Traditionally, considerable effort has been made to calculate and measure the radiation dose to the target as well as to nearby critical structures. Only recently has attention been focused also on the relatively low doses that exist far from the primary radiation beams. In several clinical scenarios, such doses have been associated with cardiac toxicity as well as an increased risk of secondary cancer induction. Out-of-field dose is a result of leakage and scatter and generally difficult to predict accurately. The present review aims to present existing data, from measurements and calculations,and discuss its implications for radiotherapy.

Allogeneic Blood and Marrow Transplant ( BMT) survivors are at high risk of secondary cancers. Although current guidelines endorse survivors following Country-specific general population screening recommendations to mitigate this risk, little is known about cancer screening adherence in Australian BMT survivors. We conducted a cross-sectional survey of 441 BMT survivors who were >1 year post transplant, to explore rates of screening for secondary cancers and to identify barriers to cancer screening recommendations. Survey instruments included the Sydney Post- BMT Survey, FACT- BMT, DASS 21, The Chronic Graft versus Host Disease ( GVHD) Activity Assessment-Patient Self-Report (Form B), the Lee Chronic GVHD Symptom Scale, Fear of Cancer Recurrence Scale, and The Post Traumatic Growth Inventory. Fifty-seven percent of respondents were male, median age 54 years, and 40% were >6 years post- BMT. Rates of cancer screening adherence were as follows: cervical 63.4%, breast 53.3%, skin 52.4%, and bowel 32.3%. Older BMT survivors and those >2 years post transplant were more likely to undergo cancer screening. Improved quality of life was associated with screening for skin, breast, and cervical cancer. Fear of cancer recurrence negatively impacted on cervical screening. For those who had not undergone screening, the majority reported not being advised to do so by their treatment team. This study is the largest and most comprehensive to date exploring cancer screening adherence in BMT survivors in Australia. These data provide the basis for health service reform to better meet the needs of BMT survivors and provide evidence to support counseling and education of both patients and professionals. [ABSTRACT FROM AUTHOR]

Background: The epidemiology of secondary cancers in childhood cancer survivors has been unknown in Asian countries. Our aim is to assess the incidence and risk factors for secondary cancers through a nationwide survey in Japan. Methods: A retrospective cohort study comprising 10,069 children who were diagnosed with cancer between 1980 and 2009 was conducted in 15 Japanese hospitals. The cumulative incidence rate was calculated using death as the competing risk and compared by the Gray method. The standardized incidence ratio (SIR) was defined as the ratio of the number of observed cancers divided by the number of expected cancers. The risk factors were analyzed using Cox regression analysis. Results: One hundred and twenty-eight patients (1.3 %) developed secondary cancers within a median follow-up of 8.4 years. The cumulative incidence rate was 1.1 % (95 % confidence interval [CI] 0.9-1.4) at 10 years and 2.6 % (95 % CI 2.1-3.3) at 20 years after primary cancer diagnosis. Sensitivity analysis, limited to 5-year survivors ( n = 5,387), confirmed these low incidence rates. The SIR of secondary cancers was 12.1 (95 % CI 10.1-14.4). In the Cox analysis, the hazard ratios for secondary cancers were 3.81 (95 % CI 1.53-9.47) for retinoblastoma, 2.78 (95 % CI 1.44-5.38) for bone/soft tissue sarcomas, and 1.81 (95 % CI 1.16-2.83) for allogeneic stem cell transplantation. Conclusions: The cumulative incidence of secondary cancers in children in Japan was not high; however, the SIR was relatively high. Retinoblastoma or sarcoma in addition to allogeneic stem cell transplantation were significant risk factors for secondary cancers. [ABSTRACT FROM AUTHOR]

Background: Addition of the anti-CD20 monoclonal antibody rituximab to chemotherapy improves response rates and survival in patients with B-cell non-Hodgkin lymphoma (NHL). However, rituximab induces a transient B-cell depletion and a dose-dependent T-cell inactivation that could impair T-cell immunosurveillance. The impact of rituximab on second primary malignancy (SPM) risk remains unclear so far. We thus carried out a systematic review to compare SPM risk among patients treated or not with rituximab. Patients and methods: We retrieved trials from MEDLINE and EMBASE and updated data presented at American Society of Hematology and American Society of Clinical Oncology meetings from 1998 to 2013.We selected randomized, controlled trials addressing newly or relapsed/progressive B-cell NHL in which randomization arms differed only from rituximab administration. Two authors extracted data and assessed the study quality. Results: We analyzed nine trials involving 4621 patients. At a median follow-up of 73 months, a total of 169 SPMs were observed in patients randomized to rituximab compared with 165 SPMs in patients not randomized to rituximab (OR = 0.88; 95% CI 0.66-1.19). The proportion of females, histology subtypes, use of rituximab in first line or in maintenance did not influence SPM risk (P = 0.94, P = 0.80, P = 0.87, P = 0.87, respectively). Cumulative exposure through prolonged administration in trials with rituximab maintenance did not contribute to an increased risk of SPM (P = 0.86). Conclusion: Our meta-analysis suggests no SPM predisposition among NHL survivors exposed to rituximab at a median follow-up of 6 years. [ABSTRACT FROM AUTHOR]

For a number of years we have been following the medical literature to find a relationship between chronic treatment with methotrexate and breast cancer occurrence, because we had had in our clinic a female patient who had had two consecutive cancers following methotrexate treatment for rheumatoid arthritis (RA). We were much surprised to find in some papers that breast cancer incidence is low in women with RA. Since then, we have found several papers explaining the low incidence of breast cancer among women being under NSAIDs, but those papers are not univocal. Methotrexate is a known antifolate agent and it has been demonstrated that dietary shortage of folate is a risk factor for breast cancer development.

Few studies have examined melanoma and non-melanoma skin cancer ( NMSC) incidence rates after a diagnosis of hairy cell leukaemia ( HCL). We assessed 267 HCL patients treated at Memorial Sloan Kettering Cancer Center ( MSKCC) and Surveillance, Epidemiology and End Results ( SEER) data for melanoma and NMSC incidence rates after HCL. Incidence data from MSKCC patients demonstrated a 10-year combined melanoma and NMSC skin cancer rate of 11·3%, melanoma 4·4% and NMSC 6·9%. Molecular analysis of skin cancers from MSKCC patients revealed activating RAS mutations in 3/9 patients, including one patient with melanoma. Of 4750 SEER patients with HCL, 55 (1·2%) had a subsequent diagnosis of melanoma. Standardized incidence ratios ( SIRs) did not show that melanoma was more common in HCL patients versus the general population ( SIR 1·3, 95% CI 0·78-2·03). Analysis of SEER HCL patients diagnosed before and after 1990 (approximately before and after purine analogue therapy was introduced) showed no evidence of an increased incidence after 1990. A better understanding of any potential association between HCL and skin cancer is highly relevant given ongoing trials using BRAF inhibitors, such as vemurafenib, for relapsed HCL, as RAS-mutant skin cancers could be paradoxically activated in these patients. [ABSTRACT FROM AUTHOR]

Purpose: Radiation-induced bystander effects have important implications in radiotherapy. Their persistence in normal cells may contribute to risk of health hazards, including cancer. This study investigates the role of radiation quality and gap junction intercellular communication (GJIC) in the propagation of harmful effects in progeny of bystander cells. Materials and methods: Confluent human skin fibroblasts were exposed to microbeam radiations with different linear energy transfer (LET) at mean absorbed doses of 0.4 Gy by which 0.036-0.4% of the cells were directly targeted by radiation. Following 20 population doublings, the cells were harvested and assayed for micronucleus formation, gene mutation and protein oxidation. Results: Our results showed that expression of stressful effects in the progeny of bystander cells is dependent on LET. The progeny of bystander cells exposed to X-rays (LET ∼6 keV/μm) or protons (LET ∼11 keV/μm) showed persistent oxidative stress, which correlated with increased micronucleus formation and mutation at the hypoxanthine-guanine phosphoribosyl-transferase ( HPRT) locus. Such effects were not observed after irradiation by carbon ions (LET ∼103 keV/μm). Interestingly, progeny of bystander cells from cultures exposed to protons or carbon ions under conditions where GJIC was inhibited harbored reduced oxidative and genetic damage. This mitigating effect was not detected when the cultures were exposed to X-rays. Conclusions: These findings suggest that cellular exposure to proton and heavy charged particle with LET properties similar to those used here can reduce the risk of lesions associated with cancer. The ability of cells to communicate via gap junctions at the time of irradiation appears to impact residual damage in progeny of bystander cells. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic stem cell transplantation is mainly indicated in bone marrow dysfunction related to blood diseases, but also in some rare diseases (adrenoleucodystrophy, mitochondrial neurogastrointestinal encephalomyopathy or MNGIE…). After decades, this treatment has proven to be efficient at the cost of numerous early and delayed side effects such as infection, graft-versus-host disease, cardiovascular complications and secondary malignancies. These complications are mainly related to the conditioning, which requires a powerful chemotherapy associated to total body irradiation (myelo-ablation) or immunosuppression (non myelo-ablation). Among side effects, the endocrine complications may be classified as 1) hormonal endocrine deficiencies (particularly gonado- and somatotropic) related to delayed consequences of chemo- and above all radiotherapy, with their consequences on growth, puberty, bone and fertility); 2) auto-immune diseases, particularly dysthyroidism; 3) secondary tumors involving either endocrine glands (thyroid carcinoma) or dependent on hormonal status (breast cancer, meningioma), favored by immune dysregulation and radiotherapy; 4) metabolic complications, especially steroid-induced diabetes and dyslipidemia with their increased cardio-vascular risk. These complications are intricate. Moreover, hormone replacement therapy can modulate the cardio-vascular or the tumoral risk of patients, already increased by radiotherapy and chemotherapy, especially steroids and anthracyclins… Therefore, patients and families should be informed of these side effects and of the importance of a long-term follow-up requiring a multidisciplinary approach. [ABSTRACT FROM AUTHOR]

Long-term outcomes following newer therapies for chronic lymphocytic leukemia (CLL) have rarely been reported. This article presents the results of the final analysis of the Polish Adult Leukemia Group PALG-CLL2 study performed 10 years from final patient enrollment. With the extended follow-up time, it was found that cladribine (2-CdA)-based combinations CMC (2-CdA, cyclophosphamide, mitoxantrone) and CC (2-CdA, cyclophosphamide) administered as first-line treatment of progressive CLL resulted in significantly longer progression-free survival, but similar overall survival compared to 2-CdA monotherapy. Furthermore, the risk of potentially fatal late adverse events including infections, autoimmune complications and, particularly, secondary neoplasms was comparable among patients treated with CMC, CC or 2-CdA. The results of our analysis support the importance of long-term outcome monitoring of randomized trials in CLL. [ABSTRACT FROM AUTHOR]

Introduction: The risk of human papillomavirus (HPV)-associated cancers is significantly higher among survivors of a childhood cancer compared to the general population. Despite this, their HPV vaccine uptake rates are lower. We examined factors related to HPV vaccine uptake among childhood cancer survivors from Western New York over 13 years following the introduction of HPV vaccines., Methods: Retrospective review of patients diagnosed with invasive or noninvasive cancerous conditions at age 9 or younger treated at Roswell Park Oishei Children's Cancer and Blood Disorder Program. We matched vaccine date information for patients aged 9-26 years between 2006 and 2020 from the New York State Immunization Information System. Demographic and cancer-related information was abstracted from electronic medical records. Cumulative vaccine uptake was assessed by Kaplan-Meier and Cox proportional hazards regression models., Results: A total of 284 patients were included in the analyses. Most were non-Hispanic/White (80.3%) and resided in a metropolitan area (81.7%). Approximately half had leukemia or lymphoma (54.9%), and most received chemotherapy. Females were more likely to initiate the HPV vaccine and did so sooner (median = 5.5 years) than males (median = 5.7 years; log-rank p = .301). Patients who were older at vaccine eligibility and males who received blood product transfusions were significantly less likely to initiate the HPV vaccine., Conclusion: While rates of HPV vaccine initiation have been increasing with time among childhood cancer survivors, they remain low overall, with differences seen by treatment and diagnosis. Our findings support the need for further research to optimize HPV vaccine delivery in cancer care., (© 2022 Wiley Periodicals LLC.)

With improvement in survival, it is important to evaluate the impact of treatment on secondary cancers in acute lymphoblastic leukaemia ( ALL) survivors. A retrospective cohort study comprising 2918 children diagnosed with ALL and enrolled on Tokyo Children's Cancer Study Group ( TCCSG) protocols between 1984 and 2005 was conducted to evaluate the incidence of secondary cancers and associated factors including treatment protocol, cranial irradiation and other characteristics of the primary ALL. Thirty-seven patients developed secondary cancers, including acute myeloid leukaemia ( n = 11), myelodysplastic syndrome ( n = 5), non- Hodgkin lymphoma ( n = 2), brain tumours ( n = 13) and other solid carcinomas ( n = 6) within a median follow-up duration of 9·5 years. The cumulative incidence of any secondary cancers was 1·0% (95% confidence interval ( CI), 0·7-1·4%) at 10 years and 2·4% (95% CI, 1·5-3·7%) at 20 years, respectively. Standardized incidence rate ratio of secondary cancers was 9·3 (95% CI, 6·5-12·8). Multivariate analyses showed an increased risk of secondary cancers associated with the recent treatment protocol and cranial irradiation. There was no evidence of a reduction in secondary cancer incidence despite marked decreases in cranial irradiation use in the recent protocols. [ABSTRACT FROM AUTHOR]

Purpose: Survivors of Hodgkin’s lymphoma (HL) are at risk of secondary tumors. We investigated the risk of secondary skin cancers after radiotherapy compared to treatment without radiation and to an age-matched population. Material and methods: We conducted a retrospective cohort study of 889 HL patients treated between 1965 and 2005. Data on secondary skin cancers and treatment fields were retrieved. Incidence rates were compared to observed rates in the Dutch population. Results: 318 skin cancers were diagnosed in 86 patients, showing significantly higher risks of skin cancers, the majority being BCC. The standardized incidence ratio (SIR) of BCC in HL survivors was significantly increased (SIR 5.2, 95% CI 4.0–6.6), especially in those aged <35years at diagnosis (SIR 8.0, 95% CI 5.8–10.7). SIR increased with longer follow-up to 15.9 (95% CI 9.1–25.9) after 35years, with 626 excess cases per 10,000 patients per year. Most (57%) skin cancers developed within the radiation fields, with significantly increased risk in patients treated with radiotherapy compared to chemotherapy alone (p =0·047, HR 2·75, 95% CI 1·01–7.45). Conclusion: Radiotherapy for HL is associated with a strongly increased long-term risk of secondary skin cancers, both compared to the general population and to treatment with chemotherapy alone. [ABSTRACT FROM AUTHOR]

Abstract: Radiation-induced (RI) secondary cancers were not a major clinical concern even as little as 15 years ago. However, advances in cancer diagnostics, therapy, and supportive care have saved numerous lives and many former cancer patients are now living for 5, 10, 20, and more years beyond their initial diagnosis. The majority of these patients have received radiotherapy as a part of their treatment regimen and are now beginning to develop secondary cancers arising from normal tissue exposure to damaging effects of ionizing radiation. Because historically patients rarely survived past the extended latency periods inherent to these RI cancers, very little effort was channeled towards the research leading to the development of therapeutic agents intended to prevent or ameliorate oncogenic effects of normal tissue exposure to radiation. The number of RI cancers is expected to increase very rapidly in the near future, but the field of cancer biology might not be prepared to address important issues related to this phenomena. One such issue is the ability to accurately differentiate between primary tumors and de novo arising secondary tumors in the same patient. Another issue is the lack of therapeutic agents intended to reduce such cancers in the future. To address these issues, large-scale epidemiological studies must be supplemented with appropriate animal modeling studies. This work reviews relevant mouse (Mus musculus) models of inbred and F1 animals and methodologies of induction of most relevant radiation-associated cancers: leukemia, lymphoma, and lung and breast cancers. Where available, underlying molecular pathologies are included. [Copyright &y& Elsevier]

Background Hodgkin lymphoma (HL) survivors have an increased morbidity and mortality from secondary cancers and cardiovascular disease (CD). We evaluate doses with involved node radiotherapy (INRT) delivered as 3D conformal radiotherapy (3D CRT), volumetric modulated arc therapy (VMAT), or proton therapy (PT), compared with the extensive Mantle Field (MF). Patients and methods For 27 patients with early-stage, mediastinal HL, treated with chemotherapy and INRT delivered as 3D CRT (30 Gy), we simulated an MF (36 Gy), INRT-VMAT and INRT-PT (30 Gy). Dose to the heart, lungs, and breasts, estimated risks of CD, lung (LC) and breast cancer (BC), and corresponding life years lost (LYL) were compared. Results 3D CRT, VMAT or PT significantly lower the dose to the heart, lungs and breasts and provide lower risk estimates compared with MF, but with substantial patient variability. The risk of CD is not significantly different for 3D CRT versus VMAT. The risk of LC and BC is highest with VMAT. For LYL, PT is the superior modern technique. Conclusions In early-stage, mediastinal HL modern radiotherapy provides superior results compared with MF. However, there is no single best radiotherapy technique for HL—the decision should be made at the individual patient level. [ABSTRACT FROM PUBLISHER]

Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Radiation Therapy for prostate cancer can increase the risk for the development of second cancers after treatment. This study highlights the fact that such second cancers within the pelvis do occur but are not as common as previously reported. In this report we also note that even among patients who develop second cancers, if detected earlier, the majority are alive 5 years after the diagnosis. OBJECTIVE To report on the incidence of secondary malignancy (SM) development after external beam radiotherapy (EBRT) and brachytherapy (BT) for prostate cancer and to compare this with a cohort contemporaneously treated with radical prostatectomy (RP)., MATERIALS AND METHODS Between 1998 and 2001, 2658 patients with localized prostate cancer were treated with RP ( n= 1348), EBRT ( n= 897) or BT ( n= 413)., Using the RP cohort as a control we compared the incidence of SMs, such as rectal or bladder cancers noted within the pelvis, and the incidence of extrapelvic SMs., RESULTS The 10-year SM-free survival for the RP, BT and EBRT cohorts were 89%, 87%, and 83%, respectively (RP vs EBRT, P= 0.002; RP vs BT, P= 0.37)., The 10-year likelihoods for bladder or colorectal cancer SM development in the RP, BT and EBRT groups were 3%, 2% and 4%, respectively ( P= 0.29)., Multivariate analysis of predictors for development of all SMs showed that older age ( P= 0.01) and history of smoking ( P < 0.001) were significant predictors for the development of a SM, while treatment intervention was not found to be a significant variable., Among 243 patients who developed a SM, the 5-year likelihood of SM-related mortality among patients with SMs in the EBRT and BT groups was 43.7% and 15.6%, respectively, compared with 26.3% in the RP cohort; P= 0.052)., CONCLUSIONS The incidence of SM after radiotherapy was not significantly different from that after RP when adjusted for patient age and smoking history., The incidence of bladder and rectal cancers was low for both EBRT- and BT-treated patients., Among patients who developed a SM, the likelihood of mortality related to the SM was not significantly different among the treatment cohorts. [ABSTRACT FROM AUTHOR]

BACKGROUND: The authors developed a framework for estimating and comparing the risks of various long-term complications on a common scale and applied it to 3 different techniques for craniospinal irradiation in patients with pediatric medulloblastoma. METHODS: Radiation dose-response parameters related to excess hazard ratios for secondary breast, lung, stomach, and thyroid cancer; heart failure, and myocardial infarction were derived from large published clinical series. Combined with age-specific and sex-specific hazards in the US general population, the dose-response analysis yielded excess hazards of complications for a cancer survivor as a function of attained age. After adjusting for competing risks of death, life years lost (LYL) were estimated based on excess hazard and prognosis of a complication for 3-dimensional conformal radiotherapy (3D CRT), volumetric modulated arc therapy (VMAT), and intensity-modulated proton therapy (IMPT). RESULTS: Lung cancer contributed most to the estimated LYL, followed by myocardial infarction, and stomach cancer. The estimates of breast or thyroid cancer incidence were higher than those for lung and stomach cancer incidence, but LYL were lower because of the relatively good prognosis. Estimated LYL ranged between 1.90 years for 3D CRT to 0.28 years for IMPT. In a paired comparison, IMPT was associated with significantly fewer LYL than both photon techniques. CONCLUSIONS: Estimating the risk of late complications is associated with considerable uncertainty, but including prognosis and attained age at an event to obtain the more informative LYL estimate added relatively little to this uncertainty. Cancer 2012. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND: Little research has identified the physical and mental health status of survivors of multiple primary cancer diagnoses. METHODS: By using data from the population-based 2009 National Health Information Survey, 154 survivors of multiple primary cancer diagnoses, 1427 survivors of a single cancer diagnosis, and 25,004 individuals without a history of cancer diagnosis were identified. The multiple cancer group was compared with the single cancer and no cancer groups with regard to physical and mental health status using analysis of covariance and binary logistic regression. RESULTS: Relative to the no cancer group, the multiple cancer group reported significantly poorer mental health status, greater lifetime, recent, and current prevalence of a variety of medical conditions and comorbidities, and more health-related disability. Although observed group differences between the multiple cancer and single cancer groups were less pronounced than those between the multiple cancer and no cancer groups, a consistent pattern was also evident; the multiple cancer group reported significantly poorer status relative to the single cancer group across a range of mental and physical health and illness-related disability indices. CONCLUSIONS: Diagnosis of 2 or more primary cancers (excluding nonmelanoma skin cancers) is associated with increased risk for poorer physical and mental health status over and above that associated with diagnosis of a single primary cancer. Survivors of multiple and single primary cancer diagnoses should be considered as distinct subgroups, and increased attention should be devoted to the unique status and needs of survivors of multiple primary cancer diagnoses. Cancer 2012;3645-3653. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]

Abstract: Physical models are increasingly used to predict acute and late effects resulting from radiation therapy. These models utilise measured and calculated microdosimetric quantities, and are increasingly used to determine the significant corrections for effective dose used in ion-beam therapy, neutron therapy and boron neutron-capture therapy. The relative biological effect (RBE) of differing radiation sources is predicted using measurable quantities such as lineal energy, which have been also generally been reproduced with calculations using Monte Carlo methods. In addition to the physical data provided by Monte Carlo modelling, in vitro studies and epidemiological data derived from cancer treatments and other exposed populations, are used in the prediction of the risk of late effects such as secondary malignancies. Monte Carlo methods are used in particular to model contaminant components. This work focuses on our understanding of the variation in RBE in photon and electron radiotherapy, how it might affect precision in the treatment of cancer, and how it provides an accurate starting point in extrapolating to prescribed doses with new therapies. In vitro transformation assays and Monte Carlo based calculations of bioeffect used for conventional photon therapy treatments over a range of energies are examined and their utility in the refinement of bioeffect models for both early and late effects are discussed. [Copyright &y& Elsevier]

Abstract: Objective: In the US, second non-ocular malignancies are the primary cause of death in retinoblastoma survivors with the germline RB1 mutation. Soft tissue sarcomas are one of the most likely malignancies to pose a risk to these patients, with leiomyosarcoma (LMS) being the most common subtype. As our cohort is followed for a longer period, we discover new second malignancy risks for these patients. Methods: We estimated the risk for uterine leiomyosarcoma (ULMS) in a cohort of 1854 patients with retinoblastoma who were diagnosed at two US institutions from 1914 through 1996. The standardized incidence ratio and excess absolute risk were calculated by comparison with population data from the Connecticut Tumor Registry or from National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database. The cumulative risk at 50years of age was also calculated. Results: Seven of 525 female hereditary retinoblastoma patients developed ULMS. Five of these patients were used in the risk analysis, resulting in an excess risk of 3.87 per 10,000 women. Among hereditary patients who developed ULMS the excess risk increases dramatically with age: to 20/10,000 for female hereditary retinoblastoma patients aged between 30 and 39years, and to 27/10,000 for patients aged 40+ years. Conclusion: There is a substantial excess risk of ULMS in female hereditary retinoblastoma patients. As more patients survive into their thirties, this number is likely to increase. These findings raise the question of early childbearing, screening and prophylactic measures in hereditary retinoblastoma patients: all issues that would benefit from confirmation from other retinoblastoma cohorts, to allow for better guided counsel of these patients. [Copyright &y& Elsevier]

Abstract: Background: Secondary tumours (ST) represent a major concern in survivors of Hodgkin''s disease (HD). Breast cancer (BC) is the most frequent ST among young treated women. Material and methods: One hundred and eighty-nine women treated for HD by radiotherapy (RT) and/or chemotherapy (CT) subsequently developed 214 BCs. Results: Median age at HD diagnosis was 25 years (34% were less than 20). Median interval between HD and BC was 18.6 years, with a 42-year median age at first BC. According to the TNM classification, there were 30 (14%) T0 (non palbable lesions), 86 (40%) T1, 56 (26%) T2, 13 (6%) T3T4 and 29 (14%) T x . There were 25 (13.2%) contralateral BC. 160 (75%) and 15 (7%) tumours were infiltrating ductal and lobular carcinomas, 7 (3.3%) were other subtypes and 27 (22%) DCIS. The rate of axillary nodal involvement was 32%. Among 203 operated tumours, 79 (39%) were treated by breast conserving surgery (BCS), with RT in 56 (71%) cases. CT and hormonal treatment were delivered in 51% and 45% of the patients. With a 50-month median follow-up, local recurrence occurred in 12% of the tumours (9% after mastectomy, 21% after lumpectomy alone and 13.7% after lumpectomy with RT). Metastasis occurred in 47 (26%) patients. The risk factors were pN+, pT, high SBR grade and young age (<50 years). The ten-year overall and specific survival rates were 53% and 63.5%, respectively. The ten-year specific survival rates were 79% for pT0T1T2, 48% for pT3T4 (p =0.0002) and 79% for pN0 versus 38.5% for pN+ (p =0.00026). Among 67 deaths, 43 (73%) were due to BC. Conclusion: Patients and physicians should be aware that BC is the most frequent secondary tumour in young women treated for HD. The new RT modalities (lower doses and involved fields) may decrease the risk in the future. However, these women require a careful monitoring as from 8 to 10 years after HD treatment, combining mammography, ultrasound and MRI according to several ongoing studies. BC with whole breast irradiation is feasible in some selected cases. [Copyright &y& Elsevier]

Radiation delivery to cancer patients for radiotherapy is invariably accompanied by unwanted radiation to other parts of the patient's body. Traditionally, considerable effort has been made to calculate and measure the radiation dose to the target as well as to nearby critical structures. Only recently has attention been focused also on the relatively low doses that exist far from the primary radiation beams. In several clinical scenarios, such doses have been associated with cardiac toxicity as well as an increased risk of secondary cancer induction. Out-of-field dose is a result of leakage and scatter and generally difficult to predict accurately. The present review aims to present existing data, from measurements and calculations, and discuss its implications for radiotherapy. [ABSTRACT FROM AUTHOR]

The article explores the secondary hematopoietic malignancies in survivors of childhood cancer. The patients included in the study are those diagnosed with primary malignancy before the age of 20 years and developed a secondary hematological malignancy. It showed that lymphoma was the most common primary cancer. It was concluded that childhood cancer survivors had an increased risk of developing secondary hematological malignancies, particularly secondary acute myeloid leukemia (AML).

Copyright of Der Radiologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Summary:To evaluate the incidence, risk factors and prognosis for solid tumors after hematopoietic stem cell transplantation (HSCT) in Japan, 809 patients who had received HSCT between 1981 and 2000 were retrospectively analyzed. In all, 19 newly diagnosed secondary cancers were observed. The risk for cancer development was 2.8 times as high as that for expected cases. The cumulative incidence ratios at 5 and 10 years were 1.9 and 4.2%, respectively. The risk was significantly elevated for buccal cavity cancer (standard incidental ratio (SIR), 44.42: 95% confidence interval (CI) 17.86–91.51), esophageal cancer (SIR, 22.36: 95% CI 6.09–57.25), and cervical cancer (SIR, 8.58: 95% CI 1.04–31.01). Of 15 patients who developed solid cancers following allografting, 12 had chronic graft-versus-host disease (GVHD), and all 10 patients with squamous cell carcinoma of the buccal cavity or esophagus had chronic GVHD. On multivariate analysis, extensive chronic GVHD and age over 45 years at the time of transplantation were associated with a higher risk for solid cancers. In all, 17 patients received therapy for secondary cancers, nine of whom are still alive and the 5-year probability of survival from the diagnosis is 42.8%. Our data suggest that early detection of secondary cancers is very important in prolonging overall survival.Bone Marrow Transplantation (2005) 36, 115–121. doi:10.1038/sj.bmt.1705020 Published online 23 May 2005 [ABSTRACT FROM AUTHOR]

Purpose: To assess the potential influence of improved dose distribution with proton beams compared to conventional or intensity-modulated (IM) X-ray beams on the incidence of treatment-induced secondary cancers in pediatric oncology.Methods and Materials: Two children, one with a parameningeal rhabdomyosarcoma (RMS) and a second with a medulloblastoma, were used as models for the purpose of this study. After defining the target and critical structures, treatment plans were calculated and optimized, four for the RMS case (conventional X-ray, IM X-rays, protons, and IM protons) and three for the irradiation of the spinal axis in medulloblastoma (conventional X-ray, IM X-rays, protons). Secondary cancer incidence was estimated using a model based on Publication No. 60 of the International Commission on Radiologic Protection. This model allowed estimation of absolute risks of secondary cancer for each treatment plan based on dose-volume distributions for the nontarget organs.Results: Proton beams reduced the expected incidence of radiation-induced secondary cancers for the RMS patient by a factor of ≥2 and for the medulloblastoma case by a factor of 8 to 15 when compared with either IM or conventional X-ray plans.Conclusions: The potential for a significant reduction in secondary cancers with pediatric cancers after using proton beams (forward planned or IM) in the treatment of RMS and MBD in children and adolescents represents an additional argument supporting the development of proton therapy for most radiotherapy indications in pediatric oncology. [Copyright &y& Elsevier]

Abstract: We studied the integral radiation dose in 27 patients who had adaptive radiotherapy for bladder cancer using kilo voltage cone beam CT imaging. Compared to conventional radiotherapy the reduction in margin and choice of best plan of three for the day resulted in a lower total dose in most patients despite daily volumetric imaging. [Copyright &y& Elsevier]