Direct visualization of proton beam irradiation effects in liquids by MRI.

The main advantage proton beams offer over photon beams in radiation therapy of cancer patients is the dose maximum at their finite range, yielding a reduction in the dose deposited in healthy tissues surrounding the tumor. Since no direct method exists to measure the beam's range during dose delivery, safety margins around the tumor are applied, compromising the dose conformality and reducing the targeting accuracy. Here, we demonstrate that online MRI can visualize the proton beam and reveal its range during irradiation of liquid-filled phantoms. A clear dependence on beam energy and current was found. These results stimulate research into novel MRI-detectable beam signatures and already find application in the geometric quality assurance for magnetic resonance-integrated proton therapy systems currently under development.

High-dose planned adaptive helical tomotherapy for cutaneous angiosarcoma of the scalp.

PURPOSE: The purpose of this study was to investigate the feasibility and effectiveness of high-dose planned adaptive intensity-modulated radiation therapy (IMRT) with helical tomotherapy (HT) for cutaneous angiosarcoma (cAS) of the scalp. METHODS: This retrospective cross-sectional included a total of 12 consecutive patients with cAS of the scalp who underwent high-dose planned adaptive IMRT with HT. Prescribed doses were 72.5-74 Gy in 35-37 fractions for the gross tumor volume plus a 1-2 mm margin (PTV1), 58-60 Gy in 29-30 fractions for the clinical target volume plus a 2-3 mm margin (PTV2), and 46 Gy in 23 fractions for the clinical target volume plus a 5-15 mm margin (PTV3) over periods of 7.5, 6 and 4.5 weeks, respectively. RESULTS: The estimated 1­year and 2­year overall survival rate were 65.6% and 27.3%, respectively, and the local progression-free survival at 2 years was 74.1%. All local recurrences were either in or marginal to the PTV2 or PTV3. No local recurrence was observed in the PTV1. All patients tolerated the treatment without grade 3 or higher adverse events during the radiotherapy period. No late adverse events were observed during the follow-up period. CONCLUSION: Planned adaptive high-dose IMRT with HT has the potential to improve local control rate without increasing adverse events.

Patient-reported symptoms before adjuvant locoregional radiotherapy for breast cancer: triple-negative histology impacts the symptom burden.

BACKGROUND: Multimodal breast cancer treatment may cause side effects reflected in patient-reported outcomes and/or symptom scores at the time of treatment planning for adjuvant radiotherapy. In our department, all patients have been assessed with the Edmonton Symptom Assessment System (ESAS; a questionnaire addressing 11 major symptoms and wellbeing on a numeric scale of 0-10) at the time of treatment planning since 2016. In this study, we analyzed ESAS symptom severity before locoregional radiotherapy. PATIENTS AND METHODS: Retrospective review of 132 patients treated between 2016 and 2021 (all comers in breast-conserving or post-mastectomy settings, different radiotherapy fractionations) was performed. All ESAS items and the ESAS point sum were analyzed to identify subgroups with higher symptom burden and thus need for additional care measures. RESULTS: The biggest patient-reported issues were fatigue, pain, and sleep problems. Patients with triple negative breast cancer reported a higher symptom burden (mean 30 versus 20, p = 0.038). Patients assigned to adjuvant endocrine therapy had the lowest point sum (mean 18), followed by those on Her-2-targeting agents without chemotherapy (mean 19), those on chemotherapy with or without other drugs (mean 26), and those without systemic therapy (mean 41), p = 0.007. Those with pathologic complete response after neoadjuvant treatment had significantly lower anxiety scores (mean 0.7 versus 1.8, p = 0.03) and a trend towards lower depression scores, p = 0.09. CONCLUSION: Different surgical strategies, age, and body mass index did not impact on ESAS scores, while the type of adjuvant systemic therapy did. The effect of previous neoadjuvant treatment and unfavorable tumor biology (triple negative) emerged as important factors associated with symptom burden, albeit in different domains. ESAS data may facilitate identification of patients who should be considered for additional supportive measures to alleviate specific symptoms.

Geometric and dosimetric evaluation for breast and regional nodal auto-segmentation structures.

The accuracy of artificial intelligence (AI) generated contours for intact-breast and post-mastectomy radiotherapy plans was evaluated. Geometric and dosimetric comparisons were performed between auto-contours (ACs) and manual-contours (MCs) produced by physicians for target structures. Breast and regional nodal structures were manually delineated on 66 breast cancer patients. ACs were retrospectively generated. The characteristics of the breast/post-mastectomy chestwall (CW) and regional nodal structures (axillary [AxN], supraclavicular [SC], internal mammary [IM]) were geometrically evaluated by Dice similarity coefficient (DSC), mean surface distance, and Hausdorff Distance. The structures were also evaluated dosimetrically by superimposing the MC clinically delivered plans onto the ACs to assess the impact of utilizing ACs with target dose (Vx%) evaluation. Positive geometric correlations between volume and DSC for intact-breast, AxN, and CW were observed. Little or anti correlations between volume and DSC for IM and SC were shown. For intact-breast plans, insignificant dosimetric differences between ACs and MCs were observed for AxNV95% (p = 0.17) and SCV95% (p = 0.16), while IMNV90% ACs and MCs were significantly different. The average V95% for intact-breast MCs (98.4%) and ACs (97.1%) were comparable but statistically different (p = 0.02). For post-mastectomy plans, AxNV95% (p = 0.35) and SCV95% (p = 0.08) were consistent between ACs and MCs, while IMNV90% was significantly different. Additionally, 94.1% of AC-breasts met ΔV95% variation <5% when DSC > 0.7. However, only 62.5% AC-CWs achieved the same metrics, despite AC-CWV95% (p = 0.43) being statistically insignificant. The AC intact-breast structure was dosimetrically similar to MCs. The AC AxN and SC may require manual adjustments. Careful review should be performed for AC post-mastectomy CW and IMN before treatment planning. The findings of this study may guide the clinical decision-making process for the utilization of AI-driven ACs for intact-breast and post-mastectomy plans. Before clinical implementation of this auto-segmentation software, an in-depth assessment of agreement with each local facilities MCs is needed.

Microscopic Analysis of Heterochromatin, Euchromatin and Cohesin in Cancer Cell Models and under Anti-Cancer Treatment.

The spatial organization of euchromatin (EC) and heterochromatin (HC) appears as a cell-type specific network, which seems to have an impact on gene regulation and cell fate. The spatial organization of cohesin should thus also be characteristic for a cell type since it is involved in a TAD (topologically associating domain) formation, and thus in gene regulation or DNA repair processes. Based on the previous hypotheses and results on the general importance of heterochromatin organization on genome functions in particular, the configurations of these organizational units (EC represented by H3K4me3-positive regions, HC represented by H3K9me3-positive regions, cohesins) are investigated in the cell nuclei of different cancer and non-cancerous cell types and under different anti-cancer treatments. Confocal microscopic images of the model cell systems were used and analyzed using analytical processes of quantification created in Fiji, an imaging tool box well established in different fields of science. Human fibroblasts, breast cancer and glioblastoma cells as well as murine embryonal terato-carcinoma cells were used as these cell models and compared according to the different parameters of spatial arrangements. In addition, proliferating, quiescent and from the quiescent state reactivated fibroblasts were analyzed. In some selected cases, the cells were treated with X-rays or azacitidine. Heterogeneous results were obtained by the analyses of the configurations of the three different organizational units: granulation and a loss of H3K4me3-positive regions (EC) occurred after irradiation with 4 Gy or azacitidine treatment. While fibroblasts responded to irradiation with an increase in cohesin and granulation, in breast cancer cells, it resulted in decreases in cohesin and changes in granulation. H3K9me3-positive regions (HC) in fibroblasts experienced increased granulation, whereas in breast cancer cells, the amount of such regions increased. After azacitidine treatment, murine stem cells showed losses of cohesin and granulation and an increase in the granulation of H3K9me3-positive regions. Fibroblasts that were irradiated with 2 Gy only showed irregularities in structural amounts and granulation. Quiescent fibroblasts contained less euchromatin-related H3K4me3-positive signals and cohesin levels as well as higher heterochromatin-related H3K9me3-positive signals than non-quiescent ones. In general, fibroblasts responded more intensely to X-ray irradiation than breast cancer cells. The results indicate the usefulness of model cell systems and show that, in general, characteristic differences initially existing in chromatin and cohesin organizations result in specific responses to anti-cancer treatment.

Treatment of Orthotopic U251 Human Glioblastoma Multiforme Tumors in NRG Mice by Convection-Enhanced Delivery of Gold Nanoparticles Labeled with the ß-Particle-Emitting Radionuclide, 177Lu.

In this study, we investigated convection-enhanced delivery (CED) of 23 ± 3 nm gold nanoparticles (AuNPs) labeled with the ß-particle-emitting radionuclide 177Lu (177Lu-AuNPs) for treatment of orthotopic U251-Luc human glioblastoma multiforme (GBM) tumors in NRG mice. The cytotoxicity in vitro of 177Lu-AuNPs (0.0-2.0 MBq, 4 × 1011 AuNPs) on U251-Luc cells was also studied by a clonogenic survival assay, and DNA double-strand breaks (DSBs) caused by ß-particle emissions of 177Lu were measured by confocal immunofluorescence microscopy for γH2AX. NRG mice with U251-Luc tumors in the right cerebral hemisphere of the brain were treated by CED of 1.1 ± 0.2 MBq of 177Lu-AuNPs (4 × 1011 AuNPs). Control mice received unlabeled AuNPs or normal saline. Tumor retention of 177Lu-AuNPs was assessed by single-photon emission computed tomography/computed tomography (SPECT/CT) imaging and biodistribution studies. Radiation doses were estimated for the tumor, brain, and other organs. The effectiveness for treating GBM tumors was determined by bioluminescence imaging (BLI) and T2-weighted magnetic resonance imaging (MRI) and by Kaplan-Meier median survival. Normal tissue toxicity was assessed by monitoring body weight and hematology and blood biochemistry analyses at 14 d post-treatment. 177Lu-AuNPs (2.0 MBq, 4 × 1011 AuNPs) decreased the clonogenic survival of U251-Luc cells to 0.005 ± 0.002 and increased DNA DSBs by 14.3-fold compared to cells treated with unlabeled AuNPs or normal saline. A high proportion of 177Lu-AuNPs was retained in the U251-Luc tumor in NRG mice up to 21 d with minimal re-distribution to the brain or other organs. The radiation dose in the tumor was high (599 Gy). The dose in the normal right cerebral hemisphere of the brain excluding the tumor was 93-fold lower (6.4 Gy), and 2000-3000-fold lower doses were calculated for the contralateral left cerebral hemisphere (0.3 Gy) or cerebellum (0.2 Gy). The doses in peripheral organs were <0.1 Gy. BLI revealed almost complete tumor growth arrest in mice treated with 177Lu-AuNPs, while tumors grew rapidly in control mice. MRI at 28 d post-treatment and histological staining showed no visible tumor in mice treated with 177Lu-AuNPs but large GBM tumors in control mice. All control mice reached a humane endpoint requiring sacrifice within 39 d (normal saline) or 45 d post-treatment (unlabeled AuNPs), while 5/8 mice treated with 177Lu-AuNPs survived up to 150 d. No normal tissue toxicity was observed in mice treated with 177Lu-AuNPs. We conclude that CED of 177Lu-AuNPs was highly effective for treating U251-Luc human GBM tumors in the brain in NRG mice at amounts that were non-toxic to normal tissues. These 177Lu-AuNPs administered by CED hold promise for treating patients with GBM to prevent recurrence and improve long-term outcome.

Superparamagnetic iron oxide nanoparticles induce persistent large foci of DNA damage in human melanoma cells post-irradiation.

The synergy of superparamagnetic iron oxide nanoparticles (SPIONs) and ionizing radiation (IR), attributed to reactive oxygen species (ROS) and DNA double-strand breaks (DSBs) increase, was widely investigated in different cancers, but scarcely in melanoma. Herein, SPIONs were evaluated as radiosensitizers in A-375 human melanoma cells. Moreover, the effect of the combined treatment of SPIONs and gamma irradiation (SPIONs-IR) was assessed at the DNA level, where DSBs induction and their repair capacity were studied. SPIONs were synthesized, stabilized by poly(ethylene glycol) methyl ether and physicochemically characterized by high resolution-transmission electron microscopy (HR-TEM), X-ray diffraction and magnetometry and dynamic light scattering. The obtained nanoparticles showing superparamagnetic behavior and low dispersion in shape and sizes were tested in A-375 cells. The intracellular internalization of SPIONs was verified by HR-TEM and quantified by inductively coupled plasma atomic emission spectroscopy. Cells treated with SPIONs exhibited high ROS levels without associated cytotoxicity. Next, a significant radiosensitization in SPIONs-IR vs. control (IR) cells was demonstrated at 1 Gy of gamma radiation. Furthermore, a decreased DSBs repair capacity in SPIONs-IR vs. IR-treated cells was evidenced by the size increase of persistent phosphorylated H2AX foci at 24 h post-irradiation. In conclusion, these nanoparticles show the potential to radiosensitize melanoma cells by the induction of unrepairable DNA damage.

Relationship between imaging parameters and distortion in magnetic resonance images for gamma knife treatment planning.

In magnetic resonance imaging (MRI), it is necessary to reduce image distortion as much as possible because it suppresses the increase in the planning target volume. This study investigated the relationship between imaging parameters and image distortion when using G-frames. The images were obtained using a 1.5-T MRI system with a 09-101 Pro-MRI phantom. Image distortion was measured by changing the RF pulse mode, gradient mode, asymmetric echo, and bandwidth (BW). The image distortion was increased in the high RF mode than in the Normal mode. The image distortion increased in the following order: Whisper â‰¦ Normal < Fast in the different gradient modes. The image distortion increased in the following order: Without â‰¦ Weak < Strong in the different asymmetric echo modes. The image distortion increased in the following order: 300 Hz/pixel > 670 Hz/pixel â‰§ REF (150 Hz/pixel) in the different Bw. The relationship between parameters and image distortion was clarified in this study when G-frames were used for gamma knife therapy. There is had relationship between the parameters causing variation in the gradient magnetic field and image distortion. Therefore, these parameters should be adjusted to minimize distortion.

Intracranial hemangiopericytoma after radiation treatment: first case in the literature.

BACKGROUND: Radiation exposure is a known risk factor for meningioma but there are no data regarding hemangiopericytoma and radiation exposure. CASE DESCRIPTION: We report a 29-year-old pineoblastoma patient diagnosed with a hemangiopericytoma at a different location, after a successful surgical excision and adjuvant radiotherapy for the original tumor 4-year prior. CONCLUSION: Hemangiopericytoma emergence can be seen after radiotherapy.

Radiation Treatment Mechanisms of Cardiotoxicity: A Systematic Review.

Radiotherapy may be used alone or in combination with chemotherapy for cancer treatment. There are many mechanisms of radiation treatment exposure to toxicities. Our aim was to summarize the literature about known mechanisms of radiation-induced cardiac toxicities. We performed a systematic review of the literature on the PubMed database until October 2022 about cardiovascular toxicities and radiation therapy exposure. Only systematic reviews, meta-analyses, and reviews were selected. Out of 1429 publications screened, 43 papers met inclusion criteria and were selected for the umbrella review process. Microvascular and macrovascular complications could lead to adverse cardiac effects. Many radiotherapy-associated risk factors were responsible, such as the site of radiation treatment, beam proximity to heart tissues, total dosage, the number of radiotherapy sessions, adjuvant chemotherapeutic agents used, and patient traditional cardiovascular risk factors, patient age, and gender. Moreover, important dosage cutoff values could increase the incidence of cardiac toxicities. Finally, the time from radiation exposure to cardiac side effects was assessed. Our report highlighted mechanisms, radiation dosage values, and the timeline of cardiovascular toxicities after radiation therapy. All of the above may be used for the assessment of cardiovascular risk factors and the development of screening programs for cancer patients.

Do Radiation Oncology Residents Have a Preferred Radiation Treatment Planning Review Format?

In an era of increasing virtual communication, we aimed to investigate current formats used by radiation oncology residents for reviewing radiation treatment plans with attendings, preferences for formats, and reasons contributing to preferences. Residents enrolled in Canadian radiation oncology programs received questionnaires examining training level, typical review formats, preferred format, and reasons for preference. Analysis excluded PGY-1s due to insufficient exposure. Fifty-two residents participated. National response rate was 55%. Overall, hybrid review was the most used format (77%). Virtual review was the most preferred format (44%). Preference for virtual review was most common among junior residents (57%), while in-person review was most preferred by senior residents (45.4%). Few residents typically use their preferred format (35%). Reasons for preference varied between groups in convenience (p < 0.01), interactivity (p < 0.01), and teaching quality (p = 0.04). The persistence of e-learning suggests that virtual treatment planning education will continue to some degree. Junior residents prefer virtual review, while a clearly preferred review format was less apparent among senior residents. Preferences are multifactorial, and the trends seen in reasons for preference between formats may reflect advantages inherent to each. Progress is still needed in optimizing treatment planning education, as suggested by few residents using their preferred format. Residents and staff should collectively decide which educational format for treatment planning best meets educational needs.

More than treatment refusal: a National Cancer Database analysis of adjuvant treatment refusal and racial survival disparities among women with endometrial cancer.

BACKGROUND: Disparities in adjuvant treatment between Black and White women with endometrial cancer exist and contribute to worse outcomes among Black women. However, factors leading to disparate treatment receipt are understudied. OBJECTIVE: We examined whether patient refusal of adjuvant treatment (chemotherapy or radiation) differed between Black and White women and whether treatment refusal mediated racial disparities in survival among women with endometrial cancer. STUDY DESIGN: We used the National Cancer Database, a hospital-based cancer registry, to identify non-Hispanic Black and non-Hispanic White women diagnosed with endometrial cancer from 2004 to 2016 who either received or refused recommended radiation or chemotherapy. We used logistic regression to estimate multivariable-adjusted odds ratios and 95% confidence intervals for associations between race and treatment refusal. We also examined predictors of treatment refusal in race-specific models. Accelerated failure time models were used to estimate absolute differences in overall survival by race. We used causal mediation analysis to estimate the proportion of racial differences in overall survival attributable to racial differences in adjuvant treatment refusal. We considered the overall study population and strata defined by histology, and adjusted for sociodemographic, tumor, and facility characteristics. RESULTS: Our analysis included 75,447 endometrial cancer patients recommended to receive radiation and 60,187 endometrial cancer patients recommended to receive chemotherapy, among which 6.4% and 11.4% refused treatment, respectively. Among Black women recommended for radiation or chemotherapy, 6.4% and 9.6% refused, respectively. Among White women recommended for radiation or chemotherapy, 6.4% and 11.8% refused, respectively. After adjusting for sociodemographic variables, facility characteristics, and tumor characteristics, Black women were more likely to refuse chemotherapy than White women (adjusted odds ratio, 1.26; 95% confidence interval, 1.15-1.37), but no difference in radiation refusal was observed (adjusted odds ratio, 1.00; 95% confidence interval, 0.91-1.11). Some predictors of radiation refusal varied by race, namely income, education, histology, stage, and chemotherapy receipt (P interactions<.05), whereas predictors of chemotherapy refusal were generally similar between Black and White women. Among women recommended for radiation, Black women survived an average of 4.3 years shorter than White women, which did not seem attributable to differences in radiation refusal. Among women recommended for chemotherapy, Black women survived an average of 3.2 years shorter than White women of which 1.9 months (4.9%) could potentially be attributed to differences in chemotherapy refusal. CONCLUSION: We observed differences in chemotherapy refusal by race, and those differences may be responsible for up to about 2 months of the overall 3.2-year survival disparity between White and Black women. Radiation refusal did not explain any of the 4.3-year disparity among women recommended for radiation. Treatment refusal accounts for, at most, a small fraction of the total racial disparity in endometrial cancer survival. Although a better understanding of the reasons for patient treatment refusal and subsequent intervention may help improve outcomes for some women, other causes of disparate outcomes, particularly those reflecting the social determinants of health, must be investigated.

Decisional Conflict is Associated with Treatment Modality and not Disease Knowledge in South African Men with Prostate Cancer: Baseline Results from a Longitudinal Prospective Observational Study.

BACKGROUND: Decisional conflict (DC) is a psychological construct that an individual experiences in making a decision that involves risk, loss, regret, or challenges to one's values. This study assessed DC in a cohort of South African men undergoing curative treatment for localised prostate cancer (LPC). The objectives were to (1) to examine the association between DC and prostate cancer knowledge (PCK), demographics, state anxiety, prostate cancer anxiety and time to treatment and (2) to compare levels of DC between treatment groups [prostatectomy (RP) and external beam radiation (RT)]. METHOD: Data, comprising the Decisional Conflict Scale (DCS), Prostate Cancer Knowledge (PCK), State-Trait Anxiety Inventory (STAI-S), the Memorial Anxiety Scale for Prostate Cancer (MAX-PC) and demographic data from 83 participants of a larger prospective longitudinal observational study examining depression, anxiety and health related quality of life (DAHCaP) were analysed. RESULTS: The mean age of participants was 63 years (RP 61yrs and RT 65yrs; p< 0.001). Most were of mixed ancestry (72.3%). The total DCS scores between the treatment groups (RP 25.00 and RT 18.75; p = 0.037) and two DCS sub-scores-uncertainty (p = 0.033), and support (p = 0.048), were significantly higher in the RP group. A statistically significant negative correlation was observed between state anxiety and time between diagnosis and treatment in the RP group (Spearman's rho = -0.368; p = 0.030). There was no correlation between the DCS score and PCK within each treatment group (Spearman's rho RP = -0.249 and RT = -0.001). CONCLUSION: Decisional conflict was higher in men undergoing RP. Men were more anxious in the RP group regarding the time treatment was received from diagnosis. No correlation was observed between DC and PCK. Pre-surgical management of DC should include shared decision making (SDM) which is cognisant of patients' values facilitated by a customised decision aid.

Role of Stereotactic Radiation Therapy in Operable and Inoperable Early-Stage Non-small Cell Lung Cancer.

OPINION STATEMENT: Radiation therapy is becoming an increasingly important part of non-small cell lung cancer (NSCLC) management. Approximately 60% of all cancer patients require radiation therapy (RT) as part of their treatment. For lung cancer, this number is even higher, reaching approximately 77% of all patients, from radical to palliative modalities of RT. This percentage may even be underestimated, as it may not account for the more recent use of RT in oligometastatic lung cancer patients. Thus, we can estimate that each year there will be approximately 21,890 new lung cancer patients in the USA requiring RT. These numbers are expected to continue to rise, as lung cancer radiation techniques continue to improve. There is growing interest in determining the best treatment options for early-stage NSCLC patients. There is well-established data showing the benefit of RT for inoperable patients, and more recent encouraging data even in operable patients.

Getting back on track: a group psychoeducational intervention for patients and families living with head and neck cancer.

PURPOSE: Head and neck cancer survivors are increasing in prevalence, and 60-70% still experience at least one unmet emotional and/or physical need after treatment has ended. The purpose of this study was to determine the efficacy of a brief post-treatment psychoeducational intervention on perceived preparedness for coping with recovery using post-session evaluations. METHODS: Between August 2013 and May 2018, a two-session, multidisciplinary "getting back on track" class was delivered to head and neck cancer patients approximately 2 months following radiation treatment at Princess Margaret Cancer Centre in Toronto, Canada. Three hundred and fifty attendees completed evaluations. Statistical analyses of the 310 patients surveyed measured change in level of preparedness to cope with recovery using the b-prepared scale. Qualitative analyses provided insight into potential benefits for future patients. RESULTS: Almost two-thirds (58%) of patients reported an increase in level of preparedness in post-intervention surveys. Comparing self-reported level of preparedness among patients from before to after the class showed an increase in feeling prepared from 50 to 58%, and of those feeling very prepared, from 6 to 34%. The proportion of patients who reported feeling unprepared (11%) or neutral (33%) before the class decreased post-intervention, with 0% feeling unprepared and 7% feeling neutral. There were statistically significant differences in the ideal timing of the class, but overall attendees agreed that the class is an essential part of their recovery. CONCLUSION: Results confirm the efficacy of this brief psychoeducational intervention to improve preparedness in head and neck cancer survivors following radiation treatment.

Genetic variation in the body mass index of adult survivors of childhood acute lymphoblastic leukemia: A report from the Childhood Cancer Survivor Study and the St. Jude Lifetime Cohort.

BACKGROUND: Treatment characteristics such as cranial radiation therapy (CRT) do not fully explain adiposity risk in childhood acute lymphoblastic leukemia (ALL) survivors. This study was aimed at characterizing genetic variation related to adult body mass index (BMI) among survivors of childhood ALL. METHODS: Genetic associations of BMI among 1458 adult survivors of childhood ALL (median time from diagnosis, 20 years) were analyzed by multiple approaches. A 2-stage genome-wide association study in the Childhood Cancer Survivor Study (CCSS) and the St. Jude Lifetime Cohort Study (SJLIFE) was performed. BMI was a highly polygenic trait in the general population. Within the known loci, the BMI percent variance explained was estimated, and additive interactions (chi-square test) with CRT in the CCSS were evaluated. The role of DNA methylation in CRT interaction was further evaluated in a subsample of ALL survivors. RESULTS: In a meta-analysis of the CCSS and SJLIFE, 2 novel loci associated with adult BMI among survivors of childhood ALL (LINC00856 rs575792008 and EMR1 rs62123082; PMeta < 5E-8) were identified. It was estimated that the more than 700 known loci explained 6.2% of the variation in adult BMI in childhood ALL survivors. Within the known loci, significant main effects for 23 loci and statistical interactions with CRT at 9 loci (P < 7.0E-5) were further identified. At 2 CRT-interacting loci, DNA methylation patterns may have differed by age. CONCLUSIONS: Adult survivors of childhood ALL have genetic heritability for BMI similar to that observed in the general population. This study provides evidence that treatment with CRT can modify the effect of genetic variants on adult BMI in childhood ALL survivors.

Resected WHO grade I meningioma and predictors of local control.

INTRODUCTION: Despite optimal surgical resection, meningiomas may recur, with increasing grade and the degree of resection being predictive of risk. We hypothesize that an increasing Ki67 correlates with a higher risk of recurrence of resected WHO grade I meningiomas. METHODS: The study population consisted of patients with resected WHO grade 1 meningiomas in locations outside of the base of skull. Digitally scanned slides stained for Ki67 were analyzed using automatic image analysis software in a standardized fashion. RESULTS: Recurrence was observed in 53 (17.7%) of cases with a median follow up time of 25.8 months. Ki67 ranged from 0 to 30%. Median Ki67 was 5.1% for patients with recurrence and 3.5% for patients without recurrence. In unadjusted analyses, high Ki-67 (≥ 5 vs. < 5) vs. ≥ 5) was associated with over a twofold increased risk of recurrence (13.1% vs. 27% respectively; HR 2.1731; 95% CI [1.2534, 3.764]; p = 0.006). After Adjusting for patient or tumor characteristics, elevated Ki-67 remained significantly correlated with recurrence. Grade 4 Simpson resection was noted in 71 (23.7%) of patients and it was associated with a significantly increased risk of recurrence (HR 2.56; 95% CI [1.41, 4.6364]; p = 0.002). CONCLUSIONS: WHO grade 1 meningiomas exhibit a significant rate of recurrence following resection. While Ki-67 is not part of the WHO grading criteria of meningiomas, a value greater than 5% is an independent predictor for increased risk of local recurrence following surgical resection.

Stereotactic radiotherapy is a useful treatment option for patients with medullary thyroid cancer.

The role of radiotherapy in advanced medullary thyroid carcinoma (MTC) is confined to patients in whom surgical treatment or the administration of tyrosine kinase inhibitors are not possible or contraindicated. High fractionated radiation doses during radiosurgery or fractionated stereotactic radiotherapy are applied to reduce cancer-related symptoms and stabilize irradiated lesions. This study aimed to retrospectively evaluate the therapeutic effect of stereotactic radiotherapy in MTC patients. MATERIAL AND METHODS: The study group involved 11 MTC patients, treated due to 16 cancer lesions, mainly bone metastases (10 lesions), lymph node (2 lesions) metastases, or liver metastases (2 lesions), one primary thyroid tumor, and one MTC recurrence in the thyroid bed. The fractionated and total radiation doses ranged between 5 and 12 Gy and 8-44 Gy, respectively. Six lesions were treated with a single radiation fraction, three lesions with 2 fractions, another 6 lesions with 3 fractions, whereas the remaining one metastatic lesion with 9 fractions of stereotactic radiosurgery. RESULTS: The beneficial effect of stereotactic radiosurgery was obtained in all treated lesions. None of treated lesions progressed in the further disease course. Fourteen lesions were stable (87.5 %), including eight lesions showing progression before radiosurgery (good response). Disease control was obtained in all soft-tissue metastases. Regarding bone metastases, partial regression was achieved in 20 % lesions, whereas in 30 % lesions progressive before radiotherapy, the treatment led to disease stabilization. CONCLUSIONS: Our data pointed to the effectiveness of high-dose fractionated radiotherapy in MTC. However, an observation of a larger group of patients is required to confirm it.

Patient-reported outcome measures in patients undergoing radiotherapy for head and neck cancer.

OBJECTIVES: Head and neck (H&N) cancer patients experience significant acute side effects from treatment. This study evaluates prospectively collected patient-reported outcomes (PROs) in H&N patients undergoing radiotherapy (RT) to assess feasibility of electronically collecting PROs and to objectively document symptom acuity and trajectory during RT. MATERIALS AND METHODS: H&N patients undergoing radical RT at our multicentre institution completed a 12-item partial survey of the Vanderbilt Head & Neck Symptom Survey 2.0 prior to RT and weekly on RT. Between October 2016 and October 2018, 318 of 333 patients completed a baseline survey and at least one weekly survey. RESULTS: The average number of weekly questionnaires completed was 5 (range 1-8). The mean maximum symptom scores were highest for dysgeusia (5.8/10), pain (5.4/10), mucositis (4.8/10), weight loss due to swallowing (4.5/10) and mucus causing choking/gagging (4.3/10). On multivariate analysis, female gender, sinonasal, nasopharynx and oropharynx primaries were associated with a greater risk of moderate-severe pain (p < 0.05). Sinonasal, nasopharynx, oral cavity, oropharynx and thyroid primaries were associated with a greater risk of moderate-severe mucositis during radiation (p < 0.0001). Salivary gland, sinonasal, nasopharynx and oropharynx primaries and higher radiation dose were associated with a greater risk of moderate-severe dysgeusia (all p < 0.05). CONCLUSIONS: Electronic PRO collection during H&N cancer RT is feasible. H&N cancer patients experience significant symptoms during RT, and the most severe symptoms reported were dysgeusia, pain and mucositis. Oropharynx cancer patients reported the highest symptom scores during RT.

Technical Note: Volumetric computed tomography for radiotherapy simulation and treatment planning.

PURPOSE: For lung and liver tumors requiring radiotherapy, motion artifacts are common in 4D-CT images due to the small axial field-of-view (aFOV) of conventional CT scanners. This may negatively impact contouring and dose calculation accuracy and could lead to a geographic miss during treatment. Recent advancements in volumetric CT (vCT) enable an aFOV up to 160 mm in a single rotation, which may reduce motion artifacts. However, the impact of large aFOV on CT number required for dose calculation needs to be evaluated before clinical implementation. The objective of this study was to determine the utility of a 256-slice vCT scanner for 4D-CT simulation by evaluating image quality and generating relative electron density (RED) curves. METHODS: Images were acquired on a 256-slice GE Revolution CT scanner with 40 mm, 80 mm, 120 mm, 140 mm, and 160 mm aFOV. Image quality was assessed by evaluating CT number linearity, uniformity, noise, and low-contrast resolution. The relationship between each quality metric and aFOV was assessed. RESULTS: CT number linearity, uniformity, noise, and low-contrast resolution were within the expected range for each image set, except CT number in Teflon and Delrin, which were underestimated. Spearman correlation coefficient (ρ) showed that the CT number for Teflon (ρ = 1.0, p = 0.02), Delrin (ρ = 1.0, p = 0.02), and air (ρ = 1.0, p = 0.02) was significantly related to aFOV, while all other measurements were not. The measured deviations from expected values were not clinically significant. CONCLUSION: These results suggest that vCT can be used for CT simulation for radiation treatment planning.