Risk of Secondary Malignancies After Pelvic Radiation: A Population-based Analysis.

Background and objective: Radiation therapy has increasingly been used in the management of pelvic malignancies. However, the use of radiation continues to pose a risk of a secondary malignancy to its recipients. This study investigates the risk of secondary malignancy development following radiation for primary pelvic malignancies. Methods: A retrospective cohort review of the Surveillance, Epidemiology, and End Results database from 1975 to 2016 was performed. Primary pelvic malignancies were subdivided based on the receipt of radiation, and secondary malignancies were stratified as pelvic or nonpelvic to investigate the local effect of radiation. Key findings and limitations: A total of 2 102 192 patients were analyzed (1 189 108 with prostate, 315 026 with bladder, 88 809 with cervical, 249 535 with uterine, and 259 714 with rectal/anal cancer). The incidence rate (defined as cases per 1000 person years) of any secondary malignancies (including but not limited to secondary pelvic malignancies) was higher in radiation patients than in nonradiation patients (incidence rate ratio [IRR] 1.04, confidence interval [CI] 1.03-1.05), with significantly greater rates noted in radiation patients with prostate (IRR 1.22, CI 1.21-1.24), uterine (IRR 1.34), and cervical (IRR 1.80, CI 1.72-1.88) cancer. While the overall incidence rate of any secondary pelvic malignancy was lower in radiation patients (IRR 0.79, CI 0.78-0.81), a greater incidence was still noted in the same cohorts including radiation patients with prostate (IRR 1.42, CI 1.39-1.45), uterine (IRR 1.15, CI 1.08-1.21), and cervical (IRR 1.72, CI 1.59-1.86) cancer. Conclusions and clinical implications: Except for localized cervical cancer, when put in the context of median overall survival, the impact of radiation likely does not carry enough weight to change practice patterns. Radiation for pelvic malignancies increases the risk for several secondary malignancies, and more specifically, secondary pelvic malignancies, but with a relatively low absolute risk of secondary malignancies, the benefits of radiation warrant continued use for most pelvic malignancies. Practice changes should be considered for radiation utilization in malignancies with excellent cancer-specific survival such as cervical cancer. Patient summary: The use of radiation for the management of pelvic malignancies induces a risk of secondary malignancies to its recipients. However, the absolute risk being low, the benefits of radiation warrant its continued use, and a change in practice patterns is unlikely.

Second Malignancy Masquerading as Recurrence of Neuroendocrine Tumor.

Neuroendocrine tumors (NETs) may mimic many endocrine syndromes, including Cushing syndrome (CS) secondary to ectopic ACTH secretion. Radiotherapy (RT) is often used as adjuvant therapy for such persistent or recurrent NETs. However, RT may predispose a susceptible person to a second malignancy. Here, we reported the story of a 37-year-old male, who presented with progressive weight loss, bone pain, and shortness of breath in the emergency department. He was diagnosed with CS secondary to a carcinoid tumor in the bronchopulmonary tree a decade previous and underwent total bilateral adrenalectomy. He also underwent lobectomy, and subsequent RT for a primary NET and was in clinical remission. His presenting symptoms were considered a recurrence of pulmonary NETs. However, the biopsy suggested high-grade mucoepidermoid carcinoma (MEC). MEC of the lung is a rare tumor with a prevalence of <1% of all lung malignancies. MEC of the lung after RT for bronchial NET-causing ectopic CS has not yet been reported in the literature. The present patient did not survive despite achieving remission of CS and primary tumor because of the aggressive second malignancy attributed to RT, which was given for the primary tumor.

Second Malignancy Probabilities in Patients With Breast Cancer Treated With Conventional Versus Hypofractionated External Beam Radiation Therapy in the Adjuvant Setting.

AIMS: For women with breast cancer, seminal studies have shown that adjuvant hypofractionated external beam radiation therapy (hEBRT) maintains similar outcomes and may reduce overall costs compared with conventionally fractionated external beam radiation therapy (cEBRT). However, it is unclear whether hEBRT may be associated with differential risk of development of radiation-induced second malignancies compared with cEBRT. Because the occurrence of second malignancies is small, large databases may improve our understanding of the relative risk of second malignancies between hEBRT and cEBRT. MATERIALS AND METHODS: Using the National Cancer Database, we carried out a retrospective cohort analysis of women diagnosed with non-metastatic, stage 0-III breast cancer from 2004 to 2017. All patients had a lumpectomy or mastectomy and a follow-up time of at least 60 months after diagnosis. The probability of second malignancies in women receiving adjuvant cEBRT or hEBRT was compared using multivariable logistic regression adjusting for sociodemographic, geographical, clinical and treatment factors, allowing for relative (but not absolute) comparison of second malignancy risk. Temporal sensitivity analyses stratified by year of diagnosis and length of follow-up time were also conducted. RESULTS: Of the 125 228 women in our study, 115 576 (92.3%) received cEBRT and 9652 (7.71%) received hEBRT. The median age of the cohort was 60 (interquartile range 51-68) years at diagnosis and the median follow-up time was 99.61 (interquartile range 77.5-128.49) months. Upon adjusting for sociodemographic and clinical factors, patients who received hEBRT had no difference in relative risk than patients who received cEBRT (odds ratio 0.937, 95% confidence interval 0.869-1.010, P = 0.091). In analyses stratified by year of diagnosis, and stratified by length of follow-up, there was no difference in second malignancy probability between patients who completed hEBRT and patients who completed cEBRT. CONCLUSIONS: In this analysis of over 120 000 women with non-metastatic breast cancer, hEBRT was not associated with different odds of developing second malignancies compared with cEBRT. Our findings may inform patient counselling in the choice of radiation regimens for breast cancer and further support the safety of hypofractionated regimens for breast cancer.

Radiation-induced Undifferentiated Malignant Pituitary Tumor After 5 Years of Treatment for Cushing Disease.

The occurrence of a second neoplasm possibly constitutes an adverse and uncommon complication after radiotherapy. The incidence of a second pituitary tumor in patients irradiated for adrenocorticotropic hormone secreting pituitary adenoma is rare. We report a case of a 40-year-old female with Cushing disease who underwent surgical management followed by radiotherapy. After 5 years of initial treatment, an increase in tumor size was evident at the same location, with a significant interval growth of the parasellar component of the lesion. Histology revealed an undifferentiated highly malignant sarcoma. In the span of next 2 years, the patient was followed with 2 repeat decompression surgeries and radiotherapy because of significant recurrent compressive symptoms by locally invasive malignant tumor. Despite the best efforts, the patient remained unresponsive to multiple treatment strategies (eg, surgical resections and radiotherapy) and succumbed to death.

Life after total skin electron irradiation; A perspective through the eyes of a radiation oncologist.

Mycosis fungoides (MF) remains a challenge as a disease from its diagnosis through treatment and follow-up. The rarity of the disease and uncharacteristic clinical manifestations pose difficulty in diagnosis, and the lack of treatment facilities adds to the management woes. Though the Stanford technique is the most accepted modality of total skin electron beam therapy (TSEBT), the implementation details are still unstandardized. Different centers adopt different methodologies as per their convenience and suitability. We present a patient of MF with many dimensions of prediagnosis clinical features to the diagnosis, treatment, and follow-up with subsequent developments over a period of 24 years that may help to understand the disease and management in a better manner.

Radiation Therapy Changed the Second Malignancy Pattern in Rectal Cancer Survivors.

Background and Objectives: Radiotherapy (RT) plays an important role in the treatment for locally advanced rectal cancer patients. It can bring radio exposure together with the survival benefit. Cancer survivors are generally at an increased risk for second malignancies, and survivors receiving RT may have higher risks than survivors not receiving RT. Whether the risk of an all-site second malignancy may increase after RT is still debated. This study aims to compare the second malignancy pattern in rectal cancer survivors after RT. Materials and Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used for analysis. In total, 49,961 rectal cancer patients (20-84 years of age) were identified between 2000 and 2012 from 18 SEER registries. All patients underwent surgery. The occurrence of second malignancies diagnosed after rectal cancer diagnosis was compared in patients who received and did not receive RT. The standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) were used. SEER*Stat was used to generate the 95% CIs for the SIR statistics using the exact method. Results: Of the total 49,961 patients, 5582 developed second malignancies. For all-site second primary malignancies, the age-adjusted SIRs were 1.14 (95% CI 1.1-1.18) and 1.00 (95% CI 0.96-1.04) in the no RT and RT groups, respectively. In 23,192 patients from the surgery-only group, 2604 had second malignancies, and in 26,769 patients who received RT, 2978 developed second malignancies. With respect to every site, the risk of secondary prostate cancer was significantly lower in the RT group (SIR = 0.39, 95% CI 0.33-0.46) than that in the surgery-only group (SIR = 1.04, 95% CI 0.96-1.12). Moreover, the risk of thyroid cancer was significantly higher in the RT group (SIR = 2.80, 95% CI 2.2-3.51) than that in the surgery-only group (SIR = 1.29, 95% CI 0.99-1.66). Conclusions: RT may change the second malignancy pattern in rectal cancer survivors; the risk of prostate cancer decreased, and the risk of thyroid cancer increased most significantly.

Sexual disparity and the risk of second primary thyroid cancer: a paradox.

Background: Despite extensive research on sex differences in primary thyroid cancer, there is a lack of data on the role of sex in the risk of developing second primary thyroid cancer (SPTC). We aimed to investigate the risk of SPTC development according to patient sex, with an emphasis concerning previous malignancy location as well as age. Methods: Cancer survivors diagnosed with SPTC were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The SEER*Stat software package obtained standardized incidence ratios (SIR) and absolute excess risks of subsequent thyroid cancer development. Results: Data for 9,730 (62.3%) females and 5,890 (37.7%) males were extracted for a total of 15,620 SPTC individuals. Asian/Pacific Islanders had the highest incidence of SPTC [SIR =2.67, 95% confidence interval (CI): 2.49-2.86]. The risk of SPTC was higher in males (SIR =2.01, 95% CI: 1.94-2.08) than when compared to females (SIR =1.83, 95% CI: 1.79-1.88; P<0.001). Head and neck tumors had significantly higher SIRs for SPTC development in males when compared to females. Conclusions: Survivors of primary malignancies have an increased risk SPTC, especially males. Our work suggests that oncologists and endocrinologists may consider the need for increased surveillance of both male and female patients given their increased risk of SPTC.

Long-term effectiveness and safety of high dose chemotherapy followed by autologous stem cell transplantation in daily practice in patients with diffuse large B-cell lymphoma.

We retrospectively evaluated long-term outcomes of high dose chemotherapy followed by autologous stem cell transplant (HDC/ASCT) in patients with diffuse large B-cell lymphoma (DLBCL). Between 2004 and 2020, 46 DLBCL patients received HDC/ASCT in our institution, including 12 patients (26.1%), who received as an upfront setting (UFS). At a median follow-up time of 69 months (range, 2-169 months), the 5-year progression-free survival (PFS) rates were 82.5% (95%CI, 46.1-95.3%) in the UFS, and 57.8% (95%CI, 38.1-73.2%) in the relapsed or refractory (R/R) patients (n=34), respectively. The 5-year PFS rates were 62.3% (95%CI, 34.0-81.3%) in primary resistant (n=13) or early relapsing (within 1 year from the initial diagnosis) patients (n=4), and 53.3% (95%CI, 25.9-74.6%) in those relapsing >1 year after the initial diagnosis (n=17), with no statistically significant difference (p=0.498). In R/R patients, multivariate analysis showed that the remission status before HDC/ASCT was an independent poor prognostic factor for progression-free survival (hazard ratio [HR], 17.0; 95%CI, 3.35-86.6; p=0.000630) and high-risk category in the international prognostic index for OS (HR, 9.39; 95%CI, 1.71-51.6; p=0.0100). The incidence of non-relapse mortality by 5 years, and 10 years were 12.2%, and 15.2%, respectively. Eleven patients (23.9%) developed second malignancies, which was the most frequent late complication after HDC/ASCT, with 5-year, and 10-year cumulative incidence of 16.9%, 22.5%, respectively. In conclusion, HDC/ASCT is effective for chemo-sensitive R/R DLBCL regardless of the timing and lines of therapy. However, careful observation is required, considering the long-term complications such as secondary malignancies.

Case report: Pulmonary synovial sarcoma in a long-term survivor of childhood Hodgkin lymphoma.

Solid organ malignancies have been reported in survivors of Hodgkin lymphoma treated with chemoradiation; however, to the best of our knowledge no cases of pulmonary synovial sarcoma have been documented in the literature in this cohort. We herein provide a detailed description of synovial sarcoma occurring in the lung of a long-term survivor of childhood Hodgkin lymphoma. A 29-year-old female never smoker with past medical history of Hodgkin lymphoma diagnosed at the age of 7 years and treated with chemotherapy and radiation therapy was admitted for management of pneumothorax. Wedge lung resection of an ulcerated subpleural nodule revealed a malignant spindle cell tumor that based on light microscopic and immunohistochemical features was classified as monophasic synovial sarcoma. The diagnosis was further confirmed by identification of SS18 (SYT) rearrangement by fluorescence in situ hybridization and SS18-SSX1 gene fusion by RNA sequencing. The case documents a rare occurrence of synovial sarcoma in a long-term survivor of childhood Hodgkin lymphoma. While comprising a typical genetic profile for synovial sarcoma, the tumor had unusual histological features such as cystic and low-grade morphology. The case suggests that synovial sarcoma falls within an expanding spectrum of secondary malignancies following prior treatment of Hodgkin lymphoma.

Whole-Genome Sequencing Reveals Mutational Signatures Related to Radiation-Induced Sarcomas and DNA-Damage-Repair Pathways.

Radiation-induced sarcoma (RIS) is a rare but serious late complication arising from radiotherapy. Despite unfavorable clinical outcomes, the genomic footprints of ionizing radiation in RIS development remain largely unknown. Hence, this study aimed to characterize RIS genomes and the genomic alterations in them. We analyzed whole-genome sequencing in 11 RIS genomes matched with normal genomes to identify somatic alterations potentially associated with RIS development. Furthermore, the abundance of mutations, mutation signatures, and structural variants in RIS were compared with those in radiation-naïve spontaneous sarcomas. The mutation abundance in RIS genomes, including one hypermutated genome, was variable. Cancer-related genes might show different types of genomic alterations. For instance, NF1, NF2, NOTCH1, NOTCH2, PIK3CA, RB1, and TP53 showed singleton somatic mutations; MYC, CDKN2A, RB1, and NF1 showed recurrent copy number alterations; and NF2, ARID1B, and RAD51B showed recurrent structural variations. The genomic footprints of nonhomologous end joining are prevalent at indels of RIS genomes compared with those in spontaneous sarcoma genomes, representing the genomic hallmark of RIS genomes. In addition, frequent chromothripsis was identified along with predisposing germline variants in the DNA-damage-repair pathways in RIS genomes. The characterization of RIS genomes on a whole-genome sequencing scale highlighted that the nonhomologous end joining pathway was associated with tumorigenesis, and it might pave the way for the development of advanced diagnostic and therapeutic strategies for RIS.

Follicular Lymphoma Secondary to Chronic Myeloid Leukemia During Treatment With Imatinib.

Tyrosine kinase inhibitors (TKIs) remain the mainstay of treatment for those with chronic myeloid leukemia (CML); nonetheless, there is concern over the possibility of additional cancers as a result of TKI use. There are not many cases in the literature where tyrosine kinase treatment caused a patient to develop secondary lymphoma. Herein we present a 49-year-old male diagnosed with CML in 2014, on Imatinib for six years with a major molecular response, who presented with generalized lymphadenopathy in July 2020. The complete evaluation was done, and histopathology and immunohistochemistry revealed follicular lymphoma. He responded well to six cycles of bendamustine and rituximab treatment (BR). It is critical for treating physicians to be aware of such occurrences, and patients on TKI must be closely monitored.

A Malignant Tumor Developed Seven Years After Small Cell Lung Cancer Treated With Etoposide-containing Chemotherapy.

BACKGROUND/AIM: Long-term survival of patients with small cell lung cancer (SCLC) is rare, and, to the best of our knowledge, there has been no SCLC patient who developed second malignancy after long-term survival. CASE REPORT: A 66-year-old woman with a history of smoking was admitted to our hospital with a nodule in her right lung. She was diagnosed with cT2aN3M0 localized-SCLC. Chest irradiation and chemotherapy including etoposide was performed. A new nodule appeared in the right lung more than 7 years after the end of treatment for SCLC. A specimen obtained by bronchoscopic biopsy was pathologically confirmed to be a non-SCLC malignancy. CONCLUSION: There is a possibility of tumor development associated with etoposide, which is known to be carcinogenic, or residual tumor development from combined type SCLC. We could not confirm whether it was second malignancy or recurrence after long-term interval. The number of long-term survivors of SCLC is likely to increase in the future. The clinical course of this patient is interesting from the perspective of long-term survival of SCLC patients and might have implications for the treatment of patients with similar clinical course in the future.

Urothelial Carcinoma With Pulmonary Tumor Thrombotic Microangiopathy After Chemotherapy for Hodgkin Lymphoma.

Treatment-related second malignancies (SMs) remain a major concern in long-term survivors of Hodgkin lymphoma (HL). In this report, the autopsy findings of a patient with HL, who was in complete remission after chemotherapy but expired of pulmonary tumor thrombotic microangiopathy (PTTM) caused by urothelial carcinoma of the renal pelvis (UCRP), were described. A 78-year-old Japanese man with a history of classical HL developed irreversible heart failure about 2.5 years after chemotherapy. The patient expired shortly after being admitted due to ineffective treatment for heart failure. However, the cause of death was not determined. The patient's autopsy findings revealed UCRP in the left kidney, as well as infiltration around the inferior vena cava and lungs, but no HL recurrence. The primary causes of mortality were respiratory and heart failure due to PTTM. Therefore, it is essential to consider the risk of SMs and search for them in patients with HL after chemotherapy.

Second malignancy probabilities in patients with prostate cancer treated with whole pelvis radiation therapy versus prostate only radiation therapy.

BACKGROUND: Whole pelvic radiation therapy (WPRT) may improve outcomes compared with prostate only radiation therapy (PORT) in some subsets of men with prostate cancer, as in the POP-RT trial. However, there is concern about increased risk of adverse effects with WPRT, including the development of radiation-induced second malignancies (SM). Given the rarity of SM, little is known about relative rates of SM between WPRT and PORT. METHODS: A retrospective cohort analysis was performed of men with nonmetastatic, node-negative prostate cancer with at least 60 months of follow-up using a national database. SM probabilities were compared in men receiving either WPRT or PORT using multivariable logistic models adjusting for clinical and sociodemographic factors. Temporal sensitivity analyses stratified by year of diagnosis and length of follow-up were also conducted. RESULTS: Of 50,237 patients in the study, 39,338 (78.4%) received PORT, and 10,899 (21.7%) received WPRT. Median follow-up was 106.2 months (interquartile range 82.32-132.25). Crude probabilities of SM were 9.16% for WPRT and 8.88% for PORT. The adjusted odds ratio (AOR) for development of SM with PORT versus WPRT was 1.046 (95% confidence interval 0.968-1.130). Temporal sensitivity analyses by stratifying by year of diagnosis and follow-up length also did not demonstrate any significant difference in rates of SM between WPRT and PORT using AORs with WPRT as the referent. CONCLUSIONS: Retrospective analysis of over 50,000 patients did not demonstrate an association between WPRT and an increased probability of SM compared to PORT. Given the findings of POP-RT, the use of WPRT may become widespread for certain subsets of men. Thus, our findings could help guide how we counsel patients deciding between WPRT and PORT and suggest the need for prospective assessment of SM risk with WPRT and PORT.

Langerhans cell histiocytosis and associated malignancies: A retrospective analysis of 270 patients.

PURPOSE: The frequency of Langerhans cell histiocytosis (LCH) and associated malignancies (AM) is greater than statistically expected. Here, we analyze LCH-AM co-occurrence in both children and adults. METHODS: Between 1991 and 2015, data were collected by regular questionnaires to members of the Histiocyte Society and searches in PubMed and Abstract Books. Patients were grouped by age at LCH diagnosis (≤ and >18 years), and types and timing of AM occurrence were plotted with respect to the LCH diagnosis. For the statistical analysis, only the first AM were considered. RESULTS: A total of 285 LCH-AM in 270 patients were identified, 116 (43%) ≤ 18 years, and 154 (57%) >18 years. In childhood LCH-AM pairs, leukemias and myeloproliferative disorders (n = 58; 50.0%) prevailed over solid tumors (n = 43; 37.1%) and lymphoma (n = 15; 12.9%). In adults, solid tumors were reported in 61 patients (39.6%), lymphoma, and leukemias and myeloproliferative disorders in 56 (36.4%) and 37 (24.0%) patients, respectively. In most children, AM followed LCH (n = 69, 59.5%), whereas in adults, LCH and AM occurred concurrently in 69 patients (44.8%). In children, T-lineage acute lymphoblastic leukemia (ALL) and promyelocytic acute myeloid leukemia (AML) and retinoblastoma were over-represented and thyroid carcinoma in adults. CONCLUSIONS: The largest collection of data on LCH-AM to date clearly indicates inherent relationships between specific types of AM and LCH, which may be due to therapy effects, clonal evolution, and germ-line predisposition, respectively. Prospective thorough genetic analysis is warranted and will hopefully shed light on the association of LCH and second neoplasms.

Stem Cell Theory of Cancer: Rude Awakening or Bad Dream from Cancer Dormancy?

To be dormant or not depends on the origin and nature of both the cell and its niche. Similar to other cancer hallmarks, dormancy is ingrained with stemness, and stemness is embedded within dormancy. After all, cancer dormancy is dependent on multiple factors such as cell cycle arrest, metabolic inactivity, and the microenvironment. It is the net results and sum effects of a myriad of cellular interactions, interconnections, and interplays. When we unite all cancer networks and integrate all cancer hallmarks, we practice and preach a unified theory of cancer. From this perspective, we review cancer dormancy in the context of a stem cell theory of cancer. We revisit the seed and soil hypothesis of cancer. We reexamine its implications in both primary tumors and metastatic lesions. We reassess its roles in cell cycle arrest, metabolic inactivity, and stemness property. Cancer dormancy is particularly revealing when it informs us about the mysteries of late relapse, prolonged remission, and second malignancy. It is paradoxically rewarding when it delivers us the promises and power of cancer prevention and maintenance therapy in patient care.

Type of Recurrence, Cause of Death and Second Neoplasms among 737 Patients with Ductal Carcinoma In Situ of the Breast-15-Year Follow-Up.

Aim: To assess the outcomes of 737 consecutive patients with DCIS, with particular attention to the type of recurrences, other malignancies and causes of deaths. Material and Methods: A retrospective analysis of 737 consecutive DCIS patients treated in one institution in the years 1996-2011 was carried out. The cumulative recurrence risk, DFS, OS depending on the method of treatment (mastectomy, breast-conserving treatment (BCT), breast-conserving surgery (BCS)) and cause of death were assessed. Results: Sixty-six recurrences (42% DCIS, 58% invasive) were reported: 61 in the breast and 5 outside the breast. The cumulative recurrence risk after a 15-year observation after mastectomy, BCT and BCS was 3.2%, 19.5% and 31.2%, respectively (p < 0.001). The 15-year DFS after mastectomy, BCT and BCS was 72%, 65% and 48%, respectively (p < 0.001). The 15-year OS after mastectomy, BCT and BCS was 75%, 83% and 70%, respectively (p = 0.329). Deaths due to DCIS progression were reported in four (0.5%) of the overall patients and in 10.5% of patients with invasive recurrences. The majority of deaths were linked to the age of the patients or other diseases, including other neoplasms, but not DCIS. Conclusions: The highest number of recurrences was reported in patients after BCS, despite the fact that it was the lowest-risk group. In total, 79% of local recurrences were true recurrences and 58% were invasive recurrences. Local recurrences were effectively treated without an influence on the OS. The percentage of deaths due to DCIS was low and mainly concerned patients with locoregional and distant failure.

Normal tissue exposure and second malignancy risk in vertebral-body-sparing craniospinal irradiation.

The purpose of this study was to compare dose to anterior organs at risk (OARs) and quantify the risk of developing secondary malignancy (SMN) in pediatric patients treated with vertebral-body-sparing (VBS) vs vertebral body (VB) pencil beam scanning proton craniospinal irradiation (CSI). Comparative plans of VBS and VB CSI were created for 10 previously treated patients. Dose-volume histograms were used to evaluate dose to OARs. Absolute excess risk of SMN was calculated according to the organ-specific, radiation-induced cancer incidence based on the organ equivalent dose. OAR dosimetric parameters and absolute excess risk of SMN were compared for VBS and VB plans using the Kruskal-Wallis H test (α = 0.05). VBS CSI leads to significantly lower radiation dose to the heart, esophagus, kidney, liver and bowel. Excluding the vertebral body also significantly decreases the absolute excess risk of SMN for liver, esophagus and bowel. For these reasons, implementation of VBS pencil beam scanning proton CSI should be considered.

Limited Impact of Breast Cancer and Non-breast Malignancies on Survival in Older Patients with Early-Stage Breast Cancer: Results of a Large, Single-Centre, Population-Based Study.

AIMS: To analyse the disease-free survival and overall survival in older adults with breast cancer after breast-conserving therapy, focusing on the relevance of non-breast malignancy (NBM) with respect to survival rates. MATERIALS AND METHODS: Analyses were based on 1205 women aged 65 years and older with breast cancer treated with breast-conserving therapy between 1999 and 2015. Patients were divided into three age categories: 65-70, 71-75 and >75 years. Multivariate survival analysis was carried out using Cox regression analysis. RESULTS: The two youngest age categories showed excellent results, with a 12-year disease-free survival of 84.6 and 86.3%, respectively. We noted a 17.2% incidence of NBM, particularly for colon cancer and lung cancer. Most (72.9%) occurred after a diagnosis of breast cancer. Of those 72.9%, about 50% died as a result of NBM within 2 years of the diagnosis of NBM. The overall 12-year NBM-specific survival was 92.0%. The 12-year overall survival was 60.0% for all and for the three abovementioned age categories was 73.3, 54.4 and 28.4%, respectively. The cause of death for all was predominantly non-malignancy-related morbidity. CONCLUSION: The impact of breast cancer on life expectancy was limited, in particularly for women aged 65-75 years. The relevance of NBM on survival was limited.

Comparing efficacy and side effects of two systemic chemotherapy regimens for eye-preserving therapy in children with retinoblastoma.

BACKGROUND: Eye-preserving therapy in retinoblastoma comprises systemic chemotherapy, but studies analyzing the efficacy of different chemotherapy regimens are scarce. METHODS: The efficacy and side effects of two different eye-preserving chemotherapy regimens containing either vincristine, etoposide, and carboplatin (VEC) or cyclophosphamide, vincristine, etoposide, and carboplatin (CyVEC) were compared in a prospective non-interventional observational study including children diagnosed with retinoblastoma between 2013 and 2019 in Germany and Austria. Event-free eye survival (EFES) and overall eye survival (OES) of all 164 eyes treated with both regimens and risk factors were investigated. RESULTS: The EFES after VEC (2-year EFES 72.3%) was higher than after CyVEC (2-year EFES 50.4%) (plogrank  < .001). The OES did not differ significantly between the two treatment groups (plogrank  = .77; 2-year OES VEC: 82.1% vs. CyVEC: 84.8%). Advanced International Classification of Retinoblastoma (ICRB) group was prognostic for a lower EFES (plogrank  < .0001; 2-year EFES ICRB A/B/C 71.3% vs. ICRB D/E 43.0%) and OES (plogrank  < .0001; 2-year OES ICRB A/B/C 93.1% vs. ICRB D/E 61.5%). The multivariate analysis showed that age at diagnosis older than 12 months and ICRB A/B/C were associated with better EFES. No second malignancies or ototoxicities were reported after a follow-up of median 3.1 years after diagnosis of retinoblastoma (range 0.1-6.9 years). CONCLUSIONS: Despite omitting cyclophosphamide, the EFES was higher after VEC chemotherapy that contains higher doses of carboplatin compared to CyVEC. The major risk factor for enucleation was advanced ICRB tumor grouping. Randomized clinical trials on efficacy and side effects of eye-preserving chemotherapy are required to tailor treatment protocols for retinoblastoma patients.