Risk Of Second Cancer Research Articles

Long-term toxicities after allogeneic hematopoietic stem cell transplantation with or without total body irradiation: a population-based study in Korea.

To compare long-term toxicity incidences, including secondary cancer (SC) with or without total body irradiation (TBI), in Asian patients receiving allogeneic hematopoietic stem cell transplantation (HSCT) using a nationwide database. We identified 4,554 patients receiving HSCT for leukemic disease from 2009 to 2016 using the healthcare bigdata system of Korea. Incidence rate ratios (IRRs) for SC, cataracts, hypothyroidism, chronic kidney disease (CKD), myocardial infarction, or strokes were compared, and standardized incidence ratios (SIR) of SC was also estimated. TBI was conducted on 1,409 patients (30.9%). No overall survival differences based on TBI were observed. With a median follow-up duration of 58.2 months, 143 patients were diagnosed with subsequent SC (3.4%). Incidence rates per 1,000 person-year were 6.56 (95% confidence interval [CI], 4.8-8.8) and 7.23 (95% CI, 5.9-8.8) in the TBI and no-TBI groups, respectively (p = 0.594). Also, the SIR (95% CI) was not significantly increased by TBI (1.32 [0.86-1.94] vs. 1.39 [1.08-1.77] in the no-TBI group). In the young age group (0-19 years), SIRs were increased in both groups regardless of TBI (8.60 vs. 11.96). The IRRs of cataracts (1.60; 95% CI, 1.3-2.0), CKD (1.85; 95% CI, 1.3-2.6), and hypothyroidism (1.50; 95% CI, 1.1-2.1) were significantly increased after TBI. However, there were no significant differences in the occurrence of myocardial infarction and stroke according to TBI. Our results suggest that modern TBI may not additionally increase the risk of SC after allogeneic HSCT, although increased risks of other diseases were noted. Physicians should carefully consider individualized risks and benefits of TBI, with a particular focus by age group.

Incidence of Secondary Cancers After Neoadjuvant Therapy for Locally Advanced Rectal Cancer

IntroductionWhether neoadjuvant chemoradiation for locally advanced rectal cancer (LARC) induces secondary cancers is controversial. This retrospective cohort study describes the incidence of secondary cancers in LARC patients. MethodsWe compared 364 LARC patients who received conventional (50.4 Gy) or short course neoadjuvant radiation (25 Gy x 5 fractions) followed by resection to 142 patients with surgically resected rectal cancer who did not receive radiation at a single institution from 2004 to 2018. Secondary cancer was defined as any nonmetastatic noncolorectal malignancy diagnosed via biopsy or definitive imaging criteria at least 6 mo after completion of neoadjuvant therapy or after resection in the comparison group. ResultsAmong the neoadjuvant radiation group (364 patients, 40% female, age 61 ± 13 y), 32 patients developed 34 (9.3%) secondary cancers. Three cases involved a pelvic organ. Among the comparison group (142 patients, 39% female, age 64 ± 15 y), 15 patients (10.6%) developed a secondary cancer. Five cases involved pelvic organs. Secondary cancer incidence did not differ between groups. Latency period to secondary cancer diagnosis was 6.7 ± 4.3 y. Patients who received radiation underwent longer median follow-up (6.8 versus 4.5 y, P < 0.01) and were significantly less likely to develop a pelvic organ cancer (odds ratio 0.18; 95% confidence interval, 0.04-0.83; P = 0.02). No genetic mutations or cancer syndromes were identified among patients with secondary cancers. ConclusionsNeoadjuvant chemoradiation is not associated with increased secondary cancer risk in LARC patients and may have a local protective effect on pelvic organs, especially prostate. Ongoing follow-up is critical to continue risk assessment.

Survival Impact of the Second Malignancies Among the Lymphoid Neoplasm

Background: The development of the lymphoma treatment increased the number of patients with long-term survival. Due to the nature of lymphoma heterogeneous group of hematological malignancies, lymphoma treatment varies based on histopathological features. Various cytotoxic chemotherapy or radiotherapy could increase patients' risk of secondary cancer. Few studies evaluated the impact on survival of co-occurring cancers in mature lymphoid malignancies. Methods: 3953 adult patients were diagnosed with lymphoma between January 2000 and April 2021 at Yeoido and Seoul St. Mary's Hospital. The cohorts compared cohorts Standardized incidence ratio applying the Korea Central Cancer Registry (KCCR). Results: Among the patients Initially diagnosed with Mature-B cell neoplasm were 3001 patients (76.3%) and 711(18%) with mature T and NK cell neoplasm (5.6%) for Hodgkin lymphoma. Among the B cell neoplasm, 57% diffuse large B cell lymphomas (DLBCL) were the most common form of B cell type, followed by follicular lymphoma (FL) and marginal zone lymphoma. PTCL NOS was the most dominant in the T cell lymphoma, accounting for 26%, followed by Extranodal NK/T cell lymphoma 23% and angioimmunoblastic T cell lymphoma. Among B cell lymphoma, 10% of solid cancer co-occurred, and 1% of hematological can be combined; in T cell types, 6% were solid ca and 12% were hematological ca. Two hundred one (4.8%) patients had historic or newly diagnosed solid cancer cases; the median diagnosed age was 64 (27-92) years. The median time to secondary cancer after diagnosis is 2 years, most common type of secondary were hung cancer, followed by thyroid and colorectal cancer. Comparing with the Korean register, the standardized Incidence Ratio of patients with lymphoma showed the highest in thyroid ca (hazard ratio (HR) = 2.65, [95% CI 1.45-4.45]), followed by lung (HR=2.14), stomach (HR=1.79), and colon (HR=1.59), In total lymphoma patients, secondary ca. doesn't offer a poor prognostic factor in total cohorts- In the case of MZL and FL (n=737), development of secondary cancer (n=131) acts as a poor prognostic factor 5 years in than count parts (n=565), 79.4 vs. 89.1%, respectively ( p &amp;lt;0.001). Multivariate analysis showed colorectal ca ( p &amp;lt;0.001, HR = 4.83, [95% CI 5.19-1103]) and transformation to DLBCL ( p &amp;lt;0.001, HR = 4.85, [95% CI 2.68-5.79]) affect worse outcomes on OS. In the case of CLL, multivariate analysis, treatment-related AML or MDS affects inferior survival outcomes ( p =0.02, HR = 3.99, [95% CI 1.25-12.79]). Conclusions: Secondary cancers could increase mortality in low-grade B cell lymphoma patients. There were different types of secondary cancer affected overall survival by each subtype. In the low-grade lymphoma, secondary hematologic malignancies or Richter syndrome poorer patient results. This study suggested awareness of various combined malignancies by subtypes of patients with lymphoma.

Single-Cell Whole-Genome Sequencing after Chemotherapeutic Treatment Reveals Cell Type-Specific Mutational Burdens

Introduction The hematopoietic system is especially vulnerable to chemotherapeutic treatment-related long-term consequences, including clonal and malignant hematopoiesis. These diseases are caused by the acquisition of driver mutations in hematopoietic stem and progenitor cells (HSPCs). An increased rate of mutation accumulation, as identified in HSPCs of patients who receive chemotherapeutic treatment, can therefore result in disrupted blood production. Accordingly, childhood cancer survivors have a five-fold increased risk of secondary cancers, amongst which therapy-related myeloid neoplasms (t-MN) are one of the most prevalent. Here, we aim to increase the understanding of the origin of t-MN through the characterization of the short- and long-term mutational consequences of chemotherapy in different hematopoietic stem and progenitor cell types. Methods We studied the genome-wide mutation burden in the HSPC compartment at the time of an initial cancer diagnosis, following chemotherapeutic treatment, and upon a second cancer diagnosis. We performed whole-genome sequencing (WGS) of single HSPCs, including hematopoietic stem cells (HSCs, CD34+CD38-CD45RA-CD90+), multipotent progenitor cells (MPPs, CD34+CD38-CD45RA-CD90-), common myeloid progenitor cells (CMPs, CD34+CD38+CD45RA-), and granulocyte-monocyte progenitor cells (GMPs, CD34+CD38+CD45RA+). In order to obtain enough DNA for WGS, we performed clonal expansion of single cells or primary template-directed amplification of the DNA of one cell. Next, we normalized the mutation burden in each cell to the expected number of mutations (Osorio et al. Cell Reports 2018). In addition, we performed both whole genome and transcriptome sequencing of individual HSCs/MPPs. Results First, we investigated pediatric ten t-MN patients with a latency between the initial and second cancer diagnosis spanning 1-12 years. We applied WGS to clonally expanded HSPCs (CD34+CD38-CD45RA-) and found that the relative increase in mutation burden in HSPCs is restricted to the first five years after initial treatment. To gain more insight into the heterogeneous HSPC compartment, we subsequently investigated cell-type specific mutational loads based on immunophenotypic markers. So far, we have included three pediatric cancer patients with comparable treatment regimens and diagnoses, namely medium risk acute lymphoblastic leukemia. Here, we found that the mutation burden is lower in HSCs when compared to the progenitor cell types (Figure 1A). When comparing the mutation load in the HSCs to the linear mutation accumulation observed in HSCs and MPPs of healthy donors, we identified a fraction of cells overlapping with the expected mutation load based on the age of the patient (Figure 1B). These data suggest that HSCs are more protected against chemotherapy-induced mutagenesis than progenitor cells, although this protective effect varies between individual cells. Therefore, we also performed both whole genome and transcriptome sequencing from a single cell, to characterize the transcriptional state of HSCs/MPPs showing a relatively high or low mutation load within their respective cell type. Conclusions Our results indicate that primitive hematopoietic stem cells are more protected against chemotherapy-induced mutations than the more proliferative progenitor cells. In addition, we find that in t-MN patients with a long latency (&amp;gt;5 years), the mutation load in HSPCs returns to the expected baseline. Based on our data, we hypothesize that the more damaged progenitor cells may be replaced over time, fueled by the undamaged primitive stem cell pool. Thus, our results may explain why the risk of t-MN drops 5-7 years after treatment end.

Risk of secondary malignancy following radiation therapy for prostate cancer

We investigated whether prostate cancer patients treated with external beam radiation therapy (EBRT) have a higher cumulative incidence of secondary cancer compared with patients treated with radical prostatectomy (RP). We used state-wide linked data from South Australia to follow men with prostate cancer diagnosed from 2002 to 2019. The cumulative incidence of overall and site-specific secondary cancers between 5 and 15 years after treatment was estimated. Fine-Gray competing risk analyses were performed with additional sensitivity analyses to test different scenarios. A total of 7625 patients were included (54% underwent RP and 46% EBRT). Characteristics of the two groups differed significantly, with the EBRT group being older (71 vs. 64 years), having higher comorbidity burden and being more likely to die during follow-up than the RP group. Fifteen-year cumulative incidence for all secondary cancers was 27.4% and 22.3% in EBRT and RP groups, respectively. In the adjusted models, patients in the EBRT group had a significantly higher risk of genitourinary (adjusted subhazard ratio (aSHR), 2.29; 95%CI 1.16–4.51) and lung (aSHR, 1.93; 95%CI 1.05–3.56) cancers compared with patients in the RP group. However, there was no statistically significant difference between the two groups for risk of any secondary cancer, gastro-intestinal, skin or haematologic cancers. No statistically significant differences in overall risk of secondary cancer were observed in any of the sensitivity analyses and patterns for risk at specific cancer sites were relatively consistent across different age restriction and latency/time-lag scenarios. In conclusion, the increased risk of genitourinary and lung cancers among men undergoing EBRT may relate partly to treatment effects and partly to unmeasured residual confounding.

ANALISIS DOSE VOLUME HISTOGRAM (DVH) PARU-PARU DAN JANTUNG PADA KASUS KANKER PAYUDARA DENGAN TEKNIK 3DCRT

Anatomically, the background of this research focuses on Organ At Risk (OAR), specifically the lungs and the heart, which exist adjacent to the chest wall and consequently receive radiation during radiotherapy. Therefore, efforts to limit the radiation dose to OAR are necessary to minimize the risk of secondary cancers after conducting radiotherapy. The success of therapy also relies on the Treatment Planning System (TPS) for accurate dose planning. The TPS calculates the dose delivered to the patient, which is then displayed as a Dose Volume Histogram (DVH). The objective of this research is to analyze the results of a Dose Volume Histogram (DVH) for organs at Risk (OAR), specifically lungs and heart, as well as Planning Target Volume (PTV) in the cases of breast cancer using the 3DCRT technique. The research design used is a descriptive quantitative comparative analysis through observation. This study was conducted from February to March 2023 at the Radiotherapy Installation of a Hospital in the Jakarta Region. The research involved ten breast cancer patients with a total dose of 50 Gy in 25 times 6 MV energy fraction using the 3DCRT technique. Data analysis was performed using statistical tests with SPSS version 25. The result of this study showed that the average dose received by Organs At Risk (OAR) for the lungs and heart did not exceed the tolerance limits set out by RTOG 0623 (p-value &lt;0.05). The average dose value at 95% Planning Target Volume (PTV) is 0.328 (p-value &gt; 0.05), which means there is no difference in the dose received by 95% PTV or 95% PTV ≥ 4750 cGy. Meanwhile, at 107%, PTV is 0.003 (p-value &lt;0.05), which means there is a difference in the dose received by 107% PTV or 107% PTV ≤ 5350 cGy. The conclusion of this research is that compared to other techniques, and the 3DCRT technique is more often used in breast cancer radiotherapy because of its ability to provide good OAR protection with more limited resources and time. Keywords: breast cancer, 3DCRT, Dose Volume Histogram (DVH), Organ At Risk (OAR), Planning Target Volume (PTV).

Impact of proton therapy on the DNA damage induction and repair in hematopoietic stem and progenitor cells

Proton therapy is of great interest to pediatric cancer patients because of its optimal depth dose distribution. In view of healthy tissue damage and the increased risk of secondary cancers, we investigated DNA damage induction and repair of radiosensitive hematopoietic stem and progenitor cells (HSPCs) exposed to therapeutic proton and photon irradiation due to their role in radiation-induced leukemia. Human CD34+ HSPCs were exposed to 6 MV X-rays, mid- and distal spread-out Bragg peak (SOBP) protons at doses ranging from 0.5 to 2 Gy. Persistent chromosomal damage was assessed with the micronucleus assay, while DNA damage induction and repair were analyzed with the γ-H2AX foci assay. No differences were found in induction and disappearance of γ-H2AX foci between 6 MV X-rays, mid- and distal SOBP protons at 1 Gy. A significantly higher number of micronuclei was found for distal SOBP protons compared to 6 MV X-rays and mid- SOBP protons at 0.5 and 1 Gy, while no significant differences in micronuclei were found at 2 Gy. In HSPCs, mid-SOBP protons are as damaging as conventional X-rays. Distal SOBP protons showed a higher number of micronuclei in HSPCs depending on the radiation dose, indicating possible changes of the in vivo biological response.

Features of the Course of Radioinduced Breast Cancer. Clinical Observation

Introduction. Hodgkin’s lymphoma is most commonly reported in the young age of 20 to 40 years. Radiation therapy remained the first-choice option before the advent of modern chemotherapy agents. Thereafter, the risk of radioinduced breast cancer after radiotherapy with total radiation dose of 38 Gy or more increased 4.5-fold.Materials and methods. The presented clinical case demonstrates aggressive breast cancer that developed 43 years after radiation therapy for Hodgkin's lymphoma.Results and discussion. In the 1990s, chemotherapy regimens for Hodgkin’s lymphoma were not effective enough to control the disease, therefore, radiotherapy was an indispensable measure. Secondary radioinduced tumors take the second place (26 %) in the structure of mortality from Hodgkin’s lymphoma. The emergence of new, more effective chemotherapy regimens reduced the risk of secondary tumors and, in particular, breast cancer.Conclusion. At present, up to 75 % of patients with Hodgkin’s lymphoma can be cured using modern methods of chemotherapy and radiation therapy. In follow-up care, it is necessary to consider the high risk of secondary malignant neoplasms, especially lung and breast cancer.

Risk of second cancer in esophageal squamous cell carcinoma and adenocarcinoma survivors: a population-based analysis in SEER dataset.

Previous studies have reported increased risk of second cancer in both esophageal squamous cell cancer (ESCC) and esophageal adenocarcinoma (EAC) survivors. This study aimed to examine the risk and influential factors of second cancer in ESCC and EAC patients. This population-based cohort study included 7,297 ESCC patients and 11,812 EAC patients who were in 1992-2019 from the Surveillance, Epidemiology, and End Results (SEER) program in the United States. These patients were followed up until diagnosis of second cancer, death, or end of the study (December 31, 2019). We calculated standard incidence ratio (SIR) and 95% confidence interval (CI) of second cancer and performed competing-risk regression to estimate the subdistribution hazard ratios (sHR) comparing categories of patients' characteristics. After a total of 49,509.38 person-years of follow-up, 431 (5.9%) ESCC patients and 636 (5.9%) EAC patients developed a second cancer. An overall increased risk of second cancer was observed in both ESCC patients (SIR: 1.66, 95% CI: 1.51-1.83) and EAC patients (SIR: 1.11, 95% CI: 1.02-1.20). ESCC patients were at increased risk of second malignancy in oral cavity and pharynx (SIR: 12.57, 95% CI: 9.87-15.79), stomach (SIR: 3.03, 95% CI: 1.77-4.85), nose and larynx (SIR: 4.79, 95% CI: 2.47-8.37), and lung and bronchus (SIR: 2.44, 95% CI: 1.96-2.99), but decreased risk of prostate cancer (SIR: 0.73, 95% CI: 0.52-0.99). EAC patients had increased risk of second malignancies in stomach (SIR: 4.41, 95% CI: 3.23-5.89), lung and bronchus (SIR: 1.26, 95% CI: 1.02-1.54), and kidney (SIR: 1.57, 95% CI: 1.05-2.25). The risk of second cancer was higher in female ESCC patients than in males (sHR: 1.34, 95% CI: 1.11-1.63) and decreased with more advanced tumor stage in both ESCC patients (sHR: 0.62, 95% CI: 0.50-0.76 for regional stage; sHR: 0.27, 95% CI: 0.20-0.36 for distant stage) and EAC patients (sHR: 0.47, 95% CI: 0.40-0.56 for regional stage; sHR: 0.10, 95% CI: 0.07-0.13 for distant stage). Both ESCC and EAC patients are at considerable risk of certain types of second cancer.

Secondary Cancer Risk of Radiotherapy and Imaging Examination for Two Different Malignancies in One Patient

Purpose: Radiotherapy (RT), which is considered one of the critical treatments for cancer patients is also known as adjuvant therapy and palliative care, and can be attempted alone or concurrent with chemotherapy. Although RT reduces the risk of recurrence, the scattered dose may enhance the risk of secondary cancer induction; this is raising some challenges in clinical practice. To the best of our knowledge, few studies to date have assessed such effects of brain cancer adjuvant radiotherapy.&#x0D; Materials and Methods: We estimated the RT-induced risk of secondary cancer for a 45-year-old patient who had undergone radiotherapy of the head and pelvis with a 6 MV photon beam in 15 and 10 sessions, respectively. The absorbed dose by the thyroid, breast, eye lenses, region overlying ovaries, and parotids was measured using Thermoluminescent Dosimeters (TLD). Since the patient was scanned before radiotherapy, it was decided to calculate their risk as well. To evaluate the cancer risk, radiobiological models for Excess Absolute Risk (EAR), as well as Excess Relative Risk (ERR) published by the Committee on the Biological Effects of Ionizing Radiation (BEIR) in report VII, were implemented. This study thus aimed to estimate the Risk of Exposure-Induced Death (REID) and assess the radiation dose delivered to patients from Computed Tomography (CT) scans and common diagnostic nuclear medicine examinations.&#x0D; Results: The mean risk of secondary cancer for sensitive organs was calculated 3 years after radiotherapy. The highest estimated ERR was related to the region overlying right and left ovaries for pelvic radiotherapy (47.82) and (51.17), and the next highest EAR followed by right and left eye lenses for brain radiotherapy (18.09) and (15.43), respectively. In addition, other cancers arising from CT scans had the highest REID values for solid cancer (0.0015) and bone scans revealed the highest REID values for other cancers (0.00121).&#x0D; Conclusion: Calculating the corresponding risks of RT is of great significance for the patients in procedural change. Choosing proper field sizes and adapted techniques to avoid excessive doses to healthy organs can thus be a great assistance in this regard.

Secondary cancer risk assessments following the proton therapy of lung cancer as the functions of field characteristics and patient age

Introduction Radiation-induced secondary cancers relevant to proton therapy are still a main concern among cancer survivors. This study aims to determine the effects of age at exposure and treatment field size on radiation-induced secondary tumors following the proton therapy of lung cancer within out of field organs through the Monte Carlo (MC) simulation approach. Material and Methods A full MC model of ICRP-110 male phantom was simulated to calculate the absorbed dose corresponding to secondary radiations within distant organs from the tumor volume. Then, the risks of secondary malignancies were estimated by employing the recommended risk model by the Committee of Biological Effects of Ionizing Radiation (BEIR) for different treatment field sizes and various patient ages at exposure. Results The results revealed that by increasing the patient age from 25 to 45 years, lifetime attributable risk (LAR) values were decreased. Maximum and minimum mortality rates were obtained for the liver and thyroid at the fixed age of 25 years, respectively. Calculated risk values for most near organs to the tumor were higher than those for distant organs. Changing the aperture size from 5 × 5 cm2 to 8 × 10 cm2 resulted in LAR increments with maximum variations of 12.5% for the stomach and a rough variation of 1.12 times in LAR for all exposure ages. Conclusion Our work on whole-body phantom addresses the impact of age at exposure and aperture size on LAR during the proton therapy of lung cancer. To minimize secondary cancer risks relevant to proton therapy of lung cancer, extra attention should be considered.

Impact of thyroid hormone replacement on the risk of second cancer after thyroidectomy: a Korean National Cohort Study

We aimed to investigate the effect of thyroid hormone administration on the risk of second primary cancer in patients who underwent thyroidectomy for differentiated thyroid cancer. Data were extracted from the medical billing data of the Health Insurance Review and Assessment Service in South Korea. Patients between 19 and 80 years old who underwent thyroid surgery at least once between January 2009 and June 2020 were included. Data of patients with second primary cancer and control patients with matched age, sex, operation date, and follow-up duration were extracted at a ratio of 1:4. A nested case–control analysis was performed to exclude length bias to confirm the correlation between the duration of thyroid hormone administration, dose, and incidence of second primary cancer. Of the 261,598 patients who underwent surgery for thyroid cancer included in the study, 11,790 with second primary cancer and 47,160 without second primary cancer were matched. The average dose of thyroid hormone increased the adjusted odds ratio (OR) for both low (≤ 50 μg, OR 1.29, confidence interval (CI) 1.12–1.48) and high (< 100 μg, OR 1.24, CI 1.12–1.37) doses. Analyzing over time, the adjusted OR of second primary cancer increased, especially in short (≤ 1 year) (OR 1.19; CI 1.06–1.34) and long (> 5 years) duration (OR 1.25; CI 1.10–1.41). In conclusion, insufficient and excessive thyroid hormone replacement might be linked to increased second primary cancer in patients who underwent thyroidectomy for differentiated thyroid cancer.

Complete patient exposure during paediatric brain cancer treatment for photon and proton therapy techniques including imaging procedures.

In radiotherapy, especially when treating children, minimising exposure of healthy tissue can prevent the development of adverse outcomes, including second cancers. In this study we propose a validated Monte Carlo framework to evaluate the complete patient exposure during paediatric brain cancer treatment. Organ doses were calculated for treatment of a diffuse midline glioma (50.4 Gy with 1.8 Gy per fraction) on a 5-year-old anthropomorphic phantom with 3D-conformal radiotherapy, intensity modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT) and intensity modulated pencil beam scanning (PBS) proton therapy. Doses from computed tomography (CT) for planning and on-board imaging for positioning (kV-cone beam CT and X-ray imaging) accounted for the estimate of the exposure of the patient including imaging therapeutic dose. For dose calculations we used validated Monte Carlo-based tools (PRIMO, TOPAS, PENELOPE), while lifetime attributable risk (LAR) was estimated from dose-response relationships for cancer induction, proposed by Schneider etal. Out-of-field organ dose equivalent data of proton therapy are lower, with doses between 0.6 mSv (testes) and 120 mSv (thyroid), when compared to photon therapy revealing the highest out-of-field doses for IMRT ranging between 43 mSv (testes) and 575 mSv (thyroid). Dose delivered by CT ranged between 0.01 mSv (testes) and 72 mSv (scapula) while a single imaging positioning ranged between 2 μSv (testes) and 1.3 mSv (thyroid) for CBCT and 0.03 μSv (testes) and 48 μSv (scapula) for X-ray. Adding imaging dose from CT and daily CBCT to the therapeutic demonstrated an important contribution of imaging to the overall radiation burden in the course of treatment, which is subsequently used to predict the LAR, for selected organs. The complete patient exposure during paediatric brain cancer treatment was estimated by combining the results from different Monte Carlo-based dosimetry tools, showing that proton therapy allows significant reduction of the out-of-field doses and secondary cancer risk in selected organs.

Secondary Primary Cancer Risk After Radiation Therapy in Rectal Cancer: A Population-Based Cohort Study With Propensity Score Matching

BackgroundIt remains unclear whether radiation therapy (RT) has an impact on the development of secondary primary cancer (SC) in rectal cancer (RC) patients, especially within the true pelvis. AimTo examine the incidence of SC in a population-based cohort of RC after surgical treatment with or without radiation therapy (RT, NRT). Patients and MethodsThe epidemiological cohort consisting of 13,919 RC patients with primary M0 stage diagnosed between 1998 and 2019 was collected from cancer registry data of Upper Bavaria. Competing risk analyses were conducted regarding the development of SC on 11 687 first malignancies, stratified by RT/NRT. A propensity score (PS) was generated by logistic regression modeling of RT to repeat competing risk analyses on a PS-matched cohort. ResultsThe median age (interquartile range) of the epidemiological cohort was 68.9 years (60.4-76.7). About 60.8%, were men, 38.7% had UICC III, 35.8% of tumors were localized lower than 8 cm, 41.3% underwent RT. Only 17.1% of patients older than 80 years at diagnosis received RT. In general, RT patients were 5 years younger than NRT patients (65.9 years [58.0-73.0] vs. 71.3 years [62.4-79.2], P < .0001). The 20-year cumulative incidence of SC was 16.5% in RT and 17.4% in NRT patients (P = .2298). Men with RT had a lower risk of prostate cancer (HR = 0.55, 95%CI [0.34-0.91], P = .0168). In the PS-matched cohort, RT patients had a significantly higher risk of bladder cancer during follow-up (10-year cumulative incidence of 1.1% vs. 0.6% in NRT). The direction of the RT effects in men and women and different tumor sites may cancel each other. ConclusionA protective effect of RT in rectal cancer patients on developing prostate SC by half is reproduced. Further analyses studying the long-term SC risks of RT should essentially focus on stratification by sex, and focus on more recent data.

Dose comparison of robustly optimized intensity modulated proton therapy (IMPT) vs IMRT and VMAT photon plans for testicular seminoma

Background Patients with stage II seminoma have traditionally been treated with photons to the retroperitoneal and iliac space, which leads to a substantial dose bath to abdominal and pelvic organs at risk (OAR). As these patients are young and with excellent prognosis, reducing dose to OAR and thereby the risk of secondary cancer is of utmost importance. We compared IMPT to opposing IMRT fields and VMAT, assessing dose to OAR and both overall and organ-specific secondary cancer risk. Material and methods A comparative treatment planning study was conducted on planning CT-scans from ten patients with stage II seminoma, treated with photons to a ‘dog-leg’ field with doses ranging from 20 to 25 Gy and a 10 Gy sequential boost to the metastatic lymph node(s). Photon plans were either 3–4 field IMRT (Eclipse) or 1–2 arc VMAT (Pinnacle). Proton plans used robust (5 mm; 3.5%) IMPT (Eclipse), multi field optimization with 3 posterior fields supplemented by 2 anterior fields at the level of the iliac vessels. Thirty plans were generated. Mean doses to OARs were compared for IMRT vs IMPT and VMAT vs IMPT. The risk of secondary cancer was calculated according to the model described by Schneider, using excess absolute risk (EAR, per 10,000 persons per year) for body outline, stomach, duodenum, pancreas, bowel, bladder and spinal cord. Results Mean doses to all OARs were significantly lower with IMPT except similar kidney (IMRT) and spinal cord (VMAT) doses. The relative EAR for body outline was 0.59 for IMPT/IMRT (p < .05) and 0.33 for IMPT/VMAT (p < .05). Organ specific secondary cancer risk was also lower for IMPT except for pancreas and duodenum. Conclusion Proton therapy reduced radiation dose to OAR compared to both IMRT and VMAT plans, and potentially reduce the risk of secondary cancer both overall and for most OAR.

Morphea, Eosinophilic Fasciitis and Cancer: A Scoping Review.

Morphea is an autoimmune fibrotic skin disease. Eosinophilic fasciitis (EF) is considered to belong to the severe spectrum of morphea. We conducted a scoping review assessing the risk of secondary cancer among morphea/EF patients, paraneoplastic morphea/EF and morphea/EF developing secondary to cancer therapy. The search was conducted using MEDLINE, Embase, Cochrane databases for articles published from inception to September 2022 following the Preferred Reporting Items for Systematic reviews and Meta-Analyses for Scoping Reviews (PRISMA-ScR) guidelines with no language or date restrictions. Two hundred and one studies were included. Of these, 32 studies reported on secondary cancer in morphea/EF patients, 45 on paraneoplastic morphea/EF and 125 on cancer-treatment-induced morphea/EF. While the current evidence remains limited, data suggest an increased risk of secondary cutaneous and possibly pancreatic malignancy in morphea patients, particularly the generalized subtype. There were insufficient data for EF. On the other hand, paraneoplastic morphea was anecdotal, whereas several observational studies suggested that ~10% of EF cases may be paraneoplastic, primarily in the context of hematologic malignancies. Radiotherapy-induced morphea is rare, seen in ~0.2% of treated patients and is usually localized to the treatment site, except in patients with pre-existing autoimmunity. While chemotherapy-induced cases are reported, immunotherapy morphea/EF cases are emerging and are preferentially seen with PD-1 and not CTLA-4 inhibitors. This study is limited by the type of articles included (case reports, case series and observational studies), and hence, additional research on this important topic is needed.

Protocol for the T-REX-trial: tailored regional external beam radiotherapy in clinically node-negative breast cancer patients with 1-2 sentinel node macrometastases – an open, multicentre, randomised non-inferiority phase 3 trial

IntroductionModern systemic treatment has reduced incidence of regional recurrences and improved survival in breast cancer (BC). It is thus questionable whether regional radiotherapy (RT) is still beneficial in patients with...

TP53 and the Ultimate Biological Optimization Steps of Curative Radiation Oncology.

The new biological interaction cross-section-based repairable-homologically repairable (RHR) damage formulation for radiation-induced cellular inactivation, repair, misrepair, and apoptosis was applied to optimize radiation therapy. This new formulation implies renewed thinking about biologically optimized radiation therapy, suggesting that most TP53 intact normal tissues are low-dose hypersensitive (LDHS) and low-dose apoptotic (LDA). This generates a fractionation window in LDHS normal tissues, indicating that the maximum dose to organs at risk should be ≤2.3 Gy/Fr, preferably of low LET. This calls for biologically optimized treatments using a few high tumor dose-intensity-modulated light ion beams, thereby avoiding secondary cancer risks and generating a real tumor cure without a caspase-3-induced accelerated tumor cell repopulation. Light ions with the lowest possible LET in normal tissues and high LET only in the tumor imply the use of the lightest ions, from lithium to boron. The high microscopic heterogeneity in the tumor will cause local microscopic cold spots; thus, in the last week of curative ion therapy, when there are few remaining viable tumor clonogens randomly spread in the target volume, the patient should preferably receive the last 10 GyE via low LET, ensuring perfect tumor coverage, a high cure probability, and a reduced risk for adverse normal tissue reactions. Interestingly, such an approach would also ensure a steeper rise in tumor cure probability and a higher complication-free cure, as the few remaining clonogens are often fairly well oxygenated, eliminating a shallower tumor response due to inherent ion beam heterogeneity. With the improved fractionation proposal, these approaches may improve the complication-free cure probability by about 10-25% or even more.

Expression of Stem Cell Markers in High-LET Space Radiation-Induced Intestinal Tumors in Apc1638N/+ Mouse Intestine.

Estimation of cancer risk among astronauts planning to undertake future deep-space missions requires understanding the quantitative and qualitative differences in radiogenic cancers after low- and high-LET radiation exposures. Previously, we reported a multifold higher RBE for high-LET radiation-induced gastrointestinal (GI) tumorigenesis in Apc1638N/+ mice. Using the same model system, i.e., Apc1638N/+ mice, here, we report qualitative differences in the cellular phenotype of low- and high-LET radiation-induced GI tumors. Stem cell (SC) phenotypes were identified using BMI1, ALDH1, CD133, DCLK1, MSI1, and LGR5 markers in low (γ-rays)- and high (56Fe)-LET radiation-induced and spontaneous tumors. We also assessed the expression of these markers in the adjacent normal mucosa. All six of these putative SC markers were shown to be overexpressed in tumors compared to the adjacent normal intestinal tissue. A differential SC phenotype for spontaneous and radiogenic intestinal tumors in Apc1638N/+ mice was observed, where the ALDH1, BMI1, CD133, MSI1, and DCLK1 expressing cells were increased, while LGR5 expressing cells were decreased in 56Fe-induced tumors compared to γ-ray-induced and spontaneous tumors. Furthermore, higher β-catenin activation (marked by nuclear localization) was observed in 56Fe-induced tumors compared to γ and spontaneous tumors. Since differential tumor cell phenotype along with activated β-catenin may very well affect malignant progression, our findings are relevant to understanding the higher carcinogenic risk of high-LET radiation. This study has implications for the assessment of GI-cancer risk among astronauts, as well as for the estimation of secondary cancer risk among patients receiving hadron therapy, considering that our results indicate increased stemness properties after radiation.

BIG data analysis of secondary cancer risk according to thyroid cancer in patients with lipid metabolic disease

BIG data analysis of secondary cancer risk according to thyroid cancer in patients with lipid metabolic disease