Initial Radiotherapy Research Articles

Optimal timing of radiotherapy following brain metastases surgery.

There is growing evidence supporting the need for a short time delay before starting radiotherapy (RT) treatment postsurgery for most optimal responses. The timing of RT initiation and effects on outcomes have been evaluated in a variety of malignancies, but the relationship remains to be well established for brain metastasis. Retrospective study of 176 patients (aged 18-89 years) with brain metastases at a single institution (March 2009 to August 2018) who received RT following surgical resection. Time interval (≤22 and >22 days) from surgical resection to initiation of RT and any potential impact on patient outcomes were assessed. Patients who underwent RT >22 days after surgical resection had a decreased risk for all-cause mortality of 47.2% (95% CI: 8.60, 69.5%). Additionally, waiting >40 days for RT after surgical resection more than doubled the risk of tumor progression; adjusted hazard ratio 2.02 (95% CI: 1.12, 3.64). Findings indicate that a short interval delay (>22 days) following surgical resection is required before RT initiation for optimal treatment effects in brain metastasis. Our timing of RT postsurgical resection data adds definition to current heterogeneity in RT timing, which is especially important for standardized clinical trial design and patient outcomes.

Trends in heart disease mortality among breast cancer survivors in the US, 1975\u20132017

PurposeHeart disease is a significant concern among breast cancer survivors, in part due to cardiotoxic treatments including chemotherapy and radiotherapy. Long-term trends in heart disease mortality have not been well characterized. We examined heart disease mortality trends among US breast cancer survivors by treatment type.MethodsWe included first primary invasive breast cancer survivors diagnosed between 1975 and 2016 (aged 18–84; survived 12 + months; received initial chemotherapy, radiotherapy, or surgery) in the SEER-9 Database. Standardized mortality ratios (SMRs) and 10-year cumulative heart disease mortality estimates accounting for competing events were calculated by calendar year of diagnosis and initial treatment regimen. Ptrends were assessed using Poisson regression. All statistical tests were 2-sided.ResultsOf 516,916 breast cancer survivors, 40,812 died of heart disease through 2017. Heart disease SMRs declined overall from 1975–1979 to 2010–2016 (SMR 1.01 [95%CI: 0.98, 1.03] to 0.74 [0.69, 0.79], ptrend < 0.001). This decline was also observed for survivors treated with radiotherapy alone and chemotherapy plus radiotherapy. A sharper decline in heart disease SMRs was observed from 1975 to 1989 for left-sided radiotherapy, compared to right-sided. In contrast, there was a non-significant increasing trend in SMRs for chemotherapy alone, and significant by regional stage (ptrend = 0.036). Largest declines in 10-year cumulative mortality were observed from 1975–1984 to 2005–2016 among surgery only: 7.02% (95%CI: 6.80%, 7.23%) to 4.68% (95%CI: 4.39%, 4.99%) and radiotherapy alone: 6.35% (95%CI: 5.95%, 6.77%) to 2.94% (95%CI: 2.73%, 3.16%).ConclusionsWe observed declining heart disease mortality trends by most treatment types yet increasing for regional stage patients treated with chemotherapy alone, highlighting a need for additional studies with detailed treatment data and cardiovascular management throughout cancer survivorship.

Serial sampling of rectal tumors during radiotherapy: A proof-of-concept study.

153 Background: Treatment response to neoadjuvant therapy in locally advanced rectal cancer (LARC) remains heterogenous. Clinicians are guided by pre-treatment clinical assessment alone in determining neoadjuvant strategy. More must be done to uncover biological mechanisms underpinning response and resistance. We have developed a biospecimen collection protocol in LARC performing serial sampling of tumors and peripheral blood samples prior to, during and after treatment to characterize the biological evolution of this heterogenous response. Here we present early proof of concept results with a focus on the intra-tumoral immune response relating to radiotherapy (RT). Methods: Patients receiving standard-of-care neoadjuvant RT were recruited to an ethically approved study between Dec 2018 - Aug 2021. The protocol consisted of a baseline biopsy and blood sample prior to RT followed by repeat sampling at 2, 6 and 12wks after Day 1 of RT. Standard immunohistochemistry (IHC) was performed for markers of immune activity. Target capture sequencing was performed using RNA baits extracted from serial biopsies to target a 276 genes panel. Paired tumor-normal sequencing was performed. Bulk 3’ RNA seq (Lexogen Illumina Quantseq) characterized immune and inflammatory gene expression. A multiplex bead array (Luminex xPONENT) of 24 cytokines and chemokines was performed using serial plasma samples. Results: 17pts were recruited, 3 with stage IV disease. 14pts received chemoradiation and 3 pts had short-course based regimens. Treatment responses were evaluable in 14pts: graded complete in 2pts; good/ near complete in 7pts and partial/ poor in 5pts. All tumors were MSS, and most frequently mutated genes were APC (75%), KRAS (38%), NRAS (25%) , NOTCH1 (25%) and PIK3CA (25%) (n = 8). Quantseq demonstrated that the immune/ inflammatory response, as measured by interferon-gamma response and IL-6/ JAK-STAT signaling, was significantly elevated up to 12wks after Day 1 RT, with a peak at around 6wks (n = 3). Correlative IHC showed an increase in innate immune cells in pts with a favorable response at 6wks (n = 8). Cytokine/ chemokine analysis suggested patients with a favorable response demonstrated strong inflammatory (MCP1 &amp; IL-17a) responses 2 and 6wks post-RT and strong CTL (Granzyme B) and Th1 (GM-CSF &amp; IP-10) responses 12wks post-RT (n = 10). Conclusions: We show acquisition of meaningful genomic and transcriptomic material from serial biopsies in rectal cancer is possible. Early data suggest that dynamic profiling of rectal tumors demonstrates transcriptomic evolution during treatment. Specifically, we show that the immune response to radiotherapy peaks at around 6wks after initiation of RT and persists to 12wks. This supports ongoing trials of immunomodulatory treatments in combination with, and following, RT in rectal cancer. Further work is required to define differences between responders and non-responders.

Compliance of Radiotherapy Treatment at a Tertiary Cancer Center in India—A Clinical Audit

Abstract Introduction Noncompliance to planned radiotherapy (RT) treatment is associated with inferior outcomes and also serves as an indicator of quality of care offered to the patients. Identification of the rate of noncompliance and its causative factors can help us develop an insight toward implementing mitigation measures thereby improving the quality of treatment. Objective To ascertain the incidence of noncompliance and the factors affecting the same in patients offered RT appointments. Materials and Methods We retrospectively reviewed the records of patients from January 1, 2019, to December 31, 2019, who were noncompliant (defaulted RT simulation or defaulted initiation of RT or defaulted planned RT during the course of RT but excluding planned/unplanned treatment breaks or early conclusions prescribed by the treating radiation oncologist) for the planned RT treatment. Results Of the 8,607 appointments (7,699 external beam RT and 908 brachytherapy) given to the patients attending the radiation oncology outpatient department in the year 2019, a total of 197 (2.28%) patients were found to be noncomplaint. Ninety-seven patients defaulted RT simulation (49.2%), 53 defaulted RT starting (26.9%), and 47 defaulted while on RT (23.9%). Half of these had either head–neck (29.9%) or gynecological (20.8%) malignancies. Patients with breast cancers had the least noncompliance rates (0.02%). The cause for noncompliance was ascertained in 135 patients (68.5%). The common causes of noncompliance were the desire to continue treatment closer to home (21.5%) followed by logistic (17%), lack of confidence in the curative potential of the planned therapy (17%), and financial reasons (11.8%). Patients with head–neck and gynecological malignancies were more often with advanced staged disease and were planned multimodal treatment protocols. The majority of the 23 patients who defaulted palliative RT were planned for fractionated treatments (73.9%). Conclusion The incidence of noncompliance in patients planned for RT in our institute can be considered optimum. Appropriate counseling of patients at the time of scheduling appointment, upfront identification of patients at high risk of noncompliance, and assisting patients with financial and logistic challenges are imperative to ensure adherence to planned treatment schedule.

The Prognostic Impact of Radiotherapy Delays in Oropharynx Carcinoma and the Role of p16 Status.

A retrospective analysis was performed to evaluate the prognostic significance of treatment delays (TDs) for oropharynx carcinoma patients treated with definitive radiotherapy (RT), comparing p16+ versus p16- disease. Patients treated between 2012 and 2016 were analyzed (n=763). TD was defined as the time from pathologic diagnosis to initiation of RT. TD thresholds of ≤60, 61 to 90, and >90 days were used to stratify outcomes. Time on treatment (TOT) delays were estimated based on the RT fractionation. TOT delay of 1 to 3 days was compared with >3 days. Predictors of cancer-specific survival (CSS) and locoregional recurrence (LRR) were evaluated on multivariable analysis. Six hundred fifty (85%) patients had p16+ disease. On multivariable analysis, TOT delay of 1 to 3 days versus <1 day was associated with inferior CSS (hazard ratio [HR]=1.81; 95% confidence interval [CI]: 1.02-3.22). TD >90 versus ≤60 days (HR=1.68; 95% CI: 0.98-3.04) and 61 to 90 versus ≤60 days (HR=0.94; 95% CI: 0.60-1.48) was not associated with CSS. TD >90 versus ≤60 days (HR=1.29; 95% CI: 0.66-2.52), TD 61 to 90 versus ≤60 days (HR=0.98; 95% CI: 0.64-1.52), TOT 1 to 3 versus <1 day (HR=0.91; 95% CI: 0.39-2.11), and TOT >3 versus <1 day (HR=1.79; 95% CI: 0.80-3.99) were not associated with LRR. There was no interaction between p16 status and TD in relation to LRR (P=0.27) or CSS (P=0.17). TDs were not significantly associated with CSS or LRR. TOT of 1 to 3 days was associated with inferior CSS. p16 status should not be a significant factor when triaging RT start dates.

What is the appropriate skin cleaning method for nasopharyngeal cancer radiotherapy patients? A randomized controlled trial.

To determine the effect of various cleaning methods for skin with acute radiation dermatitis (RD) in patients treated for nasopharyngeal carcinoma (NPC). A total of 168 NPC inpatients were randomized, while 152 patients completed the whole trial and the data were analyzed. Patients were randomly divided into the non-washing group (Group 1), washing with water alone group (Group 2), and washing with water and soap group (Group 3). All three groups received intensity-modulated radiation therapy (IMRT) with other treatments. Follow-up from recruitment or the initial radiotherapy dose to 1month after the final radiotherapy dose. CONSORT checklist was applied as the reporting guidelines for this study. The study evaluated a range of endpoints, including incidence, timing, severity of acute RD, and quality of life (QOL). There were no allergic reactions or aggravating in both washing groups during the whole treatment. The incidence of acute RD was 100% in all three groups, while the incidence of severe RD (grades 2-3) differed among groups (Group 1 vs. Group 2 vs. Group 3: 51% vs. 23.5% vs. 18%; P = 0.001), washing moderately reduced severity compared with patients without washing. Washing also delayed the onset time of acute RD; the incidence of acute RD was significantly lower than non-washing during the first 20 fractions (P < 0.001). What is more, washing reduced the incidence of moist desquamation (25.5% vs. 5.9% vs. 6%; P = 0.003) and helped relieve itching (6.49 ± 2.09 vs. 4.90 ± 1.90 vs. 4.00 ± 1.58; P < 0.001). There were no significant differences among groups with respect to pain or burning sensation. Washing improved QOL on physical (64.37 ± 4.08 vs. 67.41 ± 4.05 vs. 71.30 ± 4.87; P < 0.001), emotional (61.47 ± 4.75 vs. 65.75 ± 3.46 vs. 70.80 ± 3.27; P < 0.001), and social functional dimensions (62.64 ± 3.57 vs. 64.87 ± 3.88 vs. 68.04 ± 4.89; P < 0.001) at the end of radiotherapy, and the outcome was similar at 1month after radiotherapy (P < 0.05). Washing with water and soap was the most effective way to reduce itching and improving QOL among the three groups (P < 0.05). Washing irradiated skin reduces the occurrence and severity of acute radiation dermatitis. ChiCTR2000038231, date of registration 09.18.2020.

THUNDER 2: THeragnostic Utilities for Neoplastic DisEases of the Rectum by MRI guided radiotherapy

BackgroundNeoadjuvant chemoradiation therapy (nCRT) is the standard treatment modality in locally advanced rectal cancer (LARC). Since response to radiotherapy (RT) is dose dependent in rectal cancer, dose escalation may lead to higher complete response rates. The possibility to predict patients who will achieve complete response (CR) is fundamental. Recently, an early tumour regression index (ERI) was introduced to predict pathological CR (pCR) after nCRT in LARC patients.The primary endpoints will be the increase of CR rate and the evaluation of feasibility of delta radiomics-based predictive MRI guided Radiotherapy (MRgRT) model.MethodsPatients affected by LARC cT2-3, N0-2 or cT4 for anal sphincter involvement N0-2a, M0 without high risk features will be enrolled in the trial. Neoadjuvant CRT will be administered using MRgRT. The initial RT treatment will consist in delivering 55 Gy in 25 fractions on Gross Tumor Volume (GTV) plus the corresponding mesorectum and 45 Gy in 25 fractions on the drainage nodes. Chemotherapy with 5-fluoracil (5-FU) or oral capecitabine will be administered continuously.A 0.35 Tesla MRI will be acquired at simulation and every day during MRgRT. At fraction 10, ERI will be calculated: if ERI will be inferior than 13.1, the patient will continue the original treatment; if ERI will be higher than 13.1 the treatment plan will be reoptimized, intensifying the dose to the residual tumor at the 11th fraction to reach 60.1 Gy.At the end of nCRT instrumental examinations are to be performed in order to restage patients. In case of stable disease or progression, the patient will undergo surgery. In case of major or complete clinical response, conservative approaches may be chosen. Patients will be followed up to evaluate toxicity and quality of life.The number of cases to be enrolled will be 63: all the patients will be treated at Fondazione Policlinico Universitario A. Gemelli IRCCS in Rome.DiscussionThis clinical trial investigates the impact of RT dose escalation in poor responder LARC patients identified using ERI, with the aim of increasing the probability of CR and consequently an organ preservation benefit in this group of patients.Trial registrationClinicalTrials.gov Identifier: NCT04815694 (25/03/2021).

An algorithm for thoracic re-irradiation using biologically effective dose: a common language on how to treat in a \u201cno-treat zone\u201d

BackgroundRe-irradiation (re-RT) is a technically challenging task for which few standardized approaches exist. This is in part due to the lack of a common platform to assess dose tolerance in relation to toxicity in the re-RT setting. To better address this knowledge gap and provide new tools for studying and developing thresholds for re-RT, we developed a novel algorithm that allows for anatomically accurate three-dimensional mapping of composite biological effective dose (BED) distributions from nominal doses (Gy).MethodsThe algorithm was designed to automatically convert nominal dose from prior treatment plans to corresponding BED value maps (voxel size 2.5 mm3 and α/β of 3 for normal tissue, BED3). Following the conversion of each plan to a BED3 dose distribution, deformable registration was used to create a summed composite re-irradiation BED3 plan for each patient who received two treatments. A proof-of-principle analysis was performed on 38 re-irradiation cases of initial stereotactic ablative radiotherapy (SABR) followed by either re-SABR or chemoradiation for isolated locoregional recurrence of early-stage non-small cell lung cancer.ResultsEvaluation of the algorithm-generated maps revealed appropriate conversion of physical dose to BED at each voxel. Of 14 patients receiving repeat SABR, there was one case each of grade 3 chest wall pain (7%), pneumonitis (7%), and dyspnea (7%). Of 24 patients undergoing repeat fractionated radiotherapy, grade 3 events were limited to two cases each of pneumonitis and dyspnea (8%). Composite BED3 dosimetry for each patient who experienced grade 2–3 events is provided and may help guide development of precise cumulative dose thresholds for organs at risk in the re-RT setting.ConclusionsThis novel algorithm successfully created a voxel-by-voxel composite treatment plan using BED values. This approach may be used to more precisely examine dosimetric predictors of toxicities and to establish more accurate normal tissue constraints for re-irradiation.

A Phase 2 Trial of Response-Based Radiation Therapy for Localized Central Nervous System Germ Cell Tumors: Patterns of Failure and Radiation Dosimetry for Nongerminomatous Germ Cell Tumors

Children's Oncology Group study ACNS1123 tested the efficacy of reduced dose and field of radiation therapy (RT) for patients with localized nongerminomatous germ cell tumors (NGGCT) who achieved a complete (CR) or partial response (PR) to chemotherapy. Here, we evaluate the quality of RT and patterns of failure for patients eligible for reduced RT in this phase 2 trial. Patients with localized NGGCT with CR/PR after induction chemotherapy received reduced RT to 30.6 Gy whole ventricular irradiation and 54 Gy tumor-bed total dose. An atlas was provided to assist with complex RT volumes. Early interventional review was performed for the initial RT plan. Complete RT plans for all patients and images of relapsed patients were centrally reviewed at completion of therapy. Between May 2012 and September 2016, 107 eligible patients were enrolled and 66 achieved a CR/PR after induction chemotherapy (± second-look surgery) and were eligible for reduced RT. Median follow-up was 4.4 years. Median age was 11.0 years (3.7-21.6), and 75% were male. Progression-free survival and overall survival at 4 years were 87.9% ± 4.0% and 92.4% ± 3.3% for 66 evaluable patients, respectively. Eight patients relapsed: 6 with isolated spinal relapse and 2 with disease in the brain and spine. After central review, 62 (94%) patients had RT targets contoured and dose delivered per protocol. None of the patients with deviations (n=4) have progressed. Patterns of failure suggest the spine is at risk for recurrence for patients with localized NGGCT who receive reduced RT after a CR/PR to induction chemotherapy. Although survival data are encouraging, the pattern of failure has influenced the next prospective trial design. RT compliance was excellent despite complexity of radiation volumes, suggesting that providing visual guidance in the form of an online atlas contributes to higher quality RT plans.

Effect of systemic inflammation biomarkers on overall survival after lung cancer radiotherapy: a single-center large-cohort study

Introduction Recent studies suggest that immune-related cells can be recruited for anti-tumor functions as well as tumor progression and the interplay between systemic inflammation and local immune response may play a major role in the development and progression of various cancers including lung cancer. Inflammatory markers, such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) can be used as surrogate biomarkers of host immune status. In this work, associations between neutrophils, lymphocytes, platelets, NLR, PLR, SII and overall survival (OS) are investigated in two cohorts of non-small cell lung cancer (NSCLC) patients treated with fractionated radiotherapy (RT) and stereotactic body radiation therapy (SBRT) and a cohort of small cell lung cancer (SCLC) patients treated with fractionated RT. Material and Methods Data from 2513 lung cancer patients were retrospectively analyzed. Baseline NLR, PLR, and SII (NLR × platelet count) were calculated from full blood test prior to RT initiation. Cox proportional hazards regression analyses were used to evaluate the association between systemic inflammation markers and known clinical factors with OS. Results The two-year OS was 42%, 63%, and 62% in the NSCLC fractionated RT, SBRT, and SCLC cohort. NLR (per 1 unit: hazard ratio [HR]: 1.04, p < 0.05) and SII (per 100 × 109/L: HR: 1.01, p < 0.05) remained the strongest independent factors of OS in multivariable Cox analyses, correcting for clinical factors in early-stage and locally advanced NSCLC and SCLC patients treated with RT. Discussion This single-center large-cohort study suggests that baseline NLR and SII are independent prognostic biomarkers associated with OS in locally advanced and early-stage NSCLC patients treated with either curative-intent fractionated RT or SBRT and SCLC patients treated with curative-intent fractionated RT. External validation is warranted to evaluate the utility of these biomarkers for patients’ stratification and adapting new treatment approaches.

CONTEMPORARY APPROACHES TO PROGNOSTICATION AND MANAGEMENT OF PELVIC RADIATION INJURIES IN GYNECOLOGICAL CANCER PATIENTS.

Rapid development of radiotherapeutic techniques and implementation of radiation therapy (RT) nanotechnologies in practice, taking into account principles of radiobiology, ensures that the planned dose will bedelivered to the target volume with minimal irradiation of healthy tissues while maintaining the guaranteed RTquality. Therefore, further advance of RT involves not only implementation of the new technologies in radiationpractice, but also the intensive developments in fields of radiation medicine and clinical radiobiology. search for optimal models of the high-energy (HDR - high dose rate) brachytherapy (BT) using the 192Irsource in comparison with effects of the reference gamma radiation from 60Co, thereby, to increase the effectivenessof chemoradiation therapy (CRT) of gynecological cancer patients (GCPs) with minimal radiation loads on criticalorgans and tissues in the tumor environment. The radiobiological study was aimed to determine the feasibility ofusing the transmembrane potential (TMP) and intensity of reactive oxygen species (ROS) production in peripheralblood lymphocytes (PBL) as predictors of radiosensitivity of non-malignant cells from the tumor environment or itsbed in order to minimize the RT complications in GCPs. Patients (n = 115) with cancer stages II-III, T2-3N0-1M0 were managed with comprehensiveconservative treatment. Three groups of patients were selected depending on the applied HDR BT method against abackground of the administered chemosensitizing agents. Blood samples of GCPs (n = 24) before the RT initiationand of apparently healthy individuals (AHIs, i.e. the control group, n = 18) were taken for the radiobiologicalresearch. Review of the direct results of 60Co or 192Ir sources use in HDR BT and of the follow-up data showed theincreased tumor positive response in the main study groups after CRT course by respectively 16.6 % and 20.1 % incomparison with 60Со HDR BT administration. Concerning local reactions it was noted that grade II radiation reactions were almost absent in the main groups. According to the results of radiobiological studies, it was establishedthat TMP level in PBL of GCPs was 1.36 times higher than in AHIs. Thus, the emerging of late radiation injuries depended on the accuracy of of individual computer planning and correct reproduction of the planned RT course, timely correction of treatment programs, use of a complexof rational medical prophylaxis, severity of tumor process and concomitant disorders, as well as on the used type ofHDR radiation sources (192Ir and 60Co). Changes in TMP values and intensity of ROS production in PBL of GCPs in comparison with AHIs, and the high values of these parameters in PBL of individual patients are a rationale to specifythem as additional indicators characterizing the possibility of radiation complications before the RT planning.

Radiation recall phenomenon after administration of the mRNA-1273 SARS-CoV-2 vaccine

Several types of SARS-CoV-2 vaccine have been developed. However, the relationship between SARS-CoV-2 vaccine and radiation therapy (RT) is unclear. Recently, there have been some reports of radiation recall phenomenon (RRP) caused by a SARS-CoV-2 vaccine. We report a case of RRP after administration of the mRNA-1273 SARS-CoV-2 vaccine. A 51-year-old female was diagnosed with breast cancer (cT4N1M0, cStage IIIB) and underwent breast total mastectomy with axillary lymph node dissection after neoadjuvant chemotherapy. After mastectomy, the patient received RT with 50 Gy in 25 fractions. An acute side effect of grade 2 dermatitis according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. occurred after RT. The patient had not started any new systemic medication after RT; however, the patient received the mRNA-1273 SARS-CoV-2 vaccine (Moderna) 1 month after the end of the initial RT. Seven days after vaccination, the patient had a skin reaction with burning sensation and redness. This skin reaction was induced in an area corresponding to the irradiation field of the chest wall. There was no skin reaction in areas other than that described. The reaction was cured within 1 week with topical hydrocortisone. This report is an interesting case report with a RPP after administration of the mRNA-1273 SARS-CoV-2 vaccine.

Spinal Cord Compression as Clinical Presentation of Malignant Hematopoietic Diseases in Pediatric Patients

Spinal cord compression (SCC) is an unusual manifestation of leukemias and lymphomas in children and defines an oncological emergency frequently unsuspected, being a cause of severe sequelae. Our aim was to analyze the characteristics of patients who presented signs or symptoms of spinal cord compression in early phases of malignant hematopoietic diseases. From November-1988 to July-2022, 3878 patients with leukemia and lymphoma were diagnosed. Of them, 36 children (0.92%) presented spinal cord compression signs/symptoms in early phases of their diagnosis: Acute Lymphoblastic Leukemia (n=18), Acute Myeloblastic Leukemia and Myeloid Sarcoma (n=7), Non-Hodgkin Lymphomas (n=9) and Hodgkin Lymphoma (n=2). Clinical characteristics, images and hematological findings, treatment strategies, results and sequelae were analyzed. Sex distribution was 3.5/1 (M/F) and the media age at diagnosis was 10 (range: 4.9-16.9) years. The most common symptoms were back pain (34/36), functional impotence (27/36) and sphincter compromise (10/36). The media time from symptom onset to diagnosis was 47,5 (range: 0-300) days. Magnetic resonance imaging was performed on 33 (92%) patients and showed epidural mass (n=16) or vertebral collapse (n=17) in all of them. Two patients received initial radiotherapy and 11 decompressive surgeries for the management of the urgency spinal cord compression. Bone marrow aspiration was the diagnostic procedure in 69% of cases. All patients received chemotherapy and 94% achieved complete remission. Severe sequelae were observed in 10 patients (paraplegia with neurogenic bladder and kyphoscoliosis). Leukemia and lymphoma should be considered as a differential diagnosis when spinal cord compression is suspected, and magnetic resonance imaging is the mandatory study to confirm this diagnosis as a matter of urgency. Bone marrow involvement was evident due to hematological alterations in 95% of cases allowing to guide the diagnosis and initiate treatment early to reduce sequelae.

A treatment planning comparison of photon stereotactic ablative radiotherapy and proton beam therapy for the re-irradiation of pelvic cancer recurrence.

BackgroundPatients who experience a pelvic cancer recurrence in or near a region that received initial radiotherapy, typically have few options for treatment. Organs at risk (OAR) have often reached their dose constraint limits leaving minimal dose remaining for standard re-irradiation (reRT). However, photon based stereotactic ablative radiotherapy (SABR) has been utilised for reRT with promising initial results although meeting OAR constraints can be challenging. Proton beam therapy (PBT) could offer an advantage.Materials and methodsSABR plans used for treatment for ten pelvic reRT patients were dosimetrically compared to PBT plans retrospectively planned using the same CT and contour data. PBT plans were created to match the CTV dose coverage of SABR treatment plans with V100% ≥95%. An ‘as low as reasonably achievable’ approach was taken to OAR tolerances with consideration of OAR dose from the initial radiation (using equivalent dose in 2 Gy fractions).ResultsDosimetric comparison of relevant OAR statistics showed a decrease in OAR dose using PBT over SABR in all patients, with equivalent target coverage. The largest statistically significant reduction was seen for the colon D0.5 cm3 with a median reduction from 13.1 Gy to 5.9 Gy. There were statistically significant dose reductions in the median dose to small bowel, sacral plexus and cauda equina.ConclusionPBT has the potential for significant dose reductions for OARs in the pelvic reRT setting compared to SABR. However, it remains unclear if the magnitude of these OAR dose reductions will translate into clinical benefit.

Geometrical Comparison and Quantitative Evaluation of 18F-FDG PET/CT- and DW-MRI-Based Target Delineation Before and During Radiotherapy for Esophageal Squamous Carcinoma.

Background and PurposeThis study aimed to evaluate the geometrical differences in and metabolic parameters of 18F-fluorodeoxyglucose positron emission tomography–computed tomography (18F-FDG PET-CT) and diffusion-weighted magnetic resonance imaging (DW-MRI) performed before and during radiotherapy (RT) for patients with esophageal cancer based on the three-dimensional CT (3DCT) medium and explore whether the high signal area derived from DW-MRI can be used as a tool for an individualized definition of the volume in need of dose escalation for esophageal squamous cancer.Materials and MethodsThirty-two patients with esophageal squamous cancer sequentially underwent repeated 3DCT, 18F-FDG PET-CT, and enhanced MRI before the initiation of RT and after the 15th fraction. All images were fused with 3DCT images through deformable registration. The gross tumor volume (GTV) was delineated based on PET Edge on the first and second PET-CT images and defined as GTVPETpre and GTVPETdur, respectively. GTVDWIpre and GTVDWIdur were delineated on the first and second DWI and corresponding T2-weighted MRI (T2W-MRI)-fused images. The maximum, mean, and peak standardized uptake values (SUVs; SUVmax, SUVmean, and SUVpeak, respectively); metabolic tumor volume (MTV); and total lesion glycolysis(TLG) and its relative changes were calculated automatically on PET. Similarly, the minimum and mean apparent diffusion coefficient (ADC; ADCmin and ADCmean) and its relative changes were measured manually using ADC maps.ResultsThe volume of GTVCT exhibited a significant positive correlation with that of GTVPET and GTVDWI (both p < 0.001). Significant differences were observed in both ADCs and 18F-FDG PET metabolic parameters before and during RT (both p < 0.001). No significant correlation was observed between SUVs and ADCs before and during RT (p = 0.072–0.944) and between ∆ADCs and ∆SUVs (p = 0.238–0.854). The conformity index and degree of inclusion of GTVPETpre to GTVDWIpre were significantly higher than those of GTVPETdur to GTVDWIdur (both p < 0.001). The maximum diameter shrinkage rate (∆LDDWI) (24%) and the tumor volume shrinkage rate (VRRDWI) (60%) based on DW-MRI during RT were significantly greater than the corresponding PET-based ∆LDPET (14%) and VRRPET (41%) rates (p = 0.017 and 0.000, respectively).ConclusionBased on the medium of CT images, there are significant differences in spatial position, biometabolic characteristics, and the tumor shrinkage rate for GTVs derived from 18F-FDG PET-CT and DW-MRI before and during RT for esophageal squamous cancer. Further studies are needed to determine if DW-MRI will be used as tool for an individualized definition of the volume in need of dose escalation.

Simulation study using the spots deletion technique in spot scanning proton beam therapy for prostate cancers.

The aim of the present study was to investigate the effects on the dose distribution and beam delivery time in spot scanning proton beam therapy (PBT) incorporating the spot deletion technique. A spot scanning plan was created for 30 patients with prostate cancer. The plan was then modified via two processes: Spots with lower weighting depositions were deleted (process A) and spots that were distant from the clinical target volume (CTV) were deleted (process B). The dose distribution to the organs at risk (OAR), the expanded CTV (exCTV), which was defined by a uniform expansion of the CTV by a radius of 5 mm, and the beam delivery time were compared among initial and modified plans. The V50 Gy [relative biological effectiveness (RBE)] to the rectum and bladder, and V60 Gy(RBE) to the urethral bulb, inhomogeneity index (INH) of the exCTV showed a difference (P=1.1x10-14, P=6.4x10-14, P=2.7x10-7, P=3.2x10-17), although only changes by process B were significant. Modified plan by process B showed the V50 Gy(RBE) to the rectum and bladder decreased by -2.4±1.6 and -2.3±1.4%, and the V60 Gy (RBE) to the urethral bulb decreased by -15.9±19.4%. The INH of the exCTV increased by 0.05±0.03%. On the other hand, modification of the initial plan by process A did not affect the dose of the OAR, exCTV or beam delivery time. In spot scanning PBT, modification of the initial radiotherapy plan by systemic deletion of spots distant from the CTV could result in a dose reduction to the OAR.

A Prospective Study of a Resorbable Intravesical Fiducial Marker for Bladder Cancer Radiation Therapy

PurposeWe conducted a prospective pilot study to evaluate safety and feasibility of TraceIT, a resorbable radiopaque hydrogel, to improve image guidance for bladder cancer radiation therapy (RT). Methods and MaterialsPatients with muscle invasive bladder cancer receiving definitive RT were eligible. TraceIT was injected intravesically around the tumor bed during maximal transurethral resection of bladder tumor. The primary endpoint was the difference between radiation treatment planning margin on daily cone beam computed tomography based on alignment to TraceIT versus standard-of-care pelvic bone anatomy. The Van Herk margin formula was used to determine the optimal planning target volume margin. TraceIT visibility, recurrence rates, and survival were estimated by Kaplan-Meier method. Toxicity was measured by Common Terminology Criteria for Adverse Events version 4.03. ResultsThe trial was fully accrued and 15 patients were analyzed. TraceIT was injected in 4 sites/patient (range, 4-6). Overall, 94% (95% confidence interval [CI], 90%-98%) of injection sites were radiographically visible at RT initiation versus 71% (95% CI, 62%-81%) at RT completion. The median duration of radiographic visibility for injection sites was 106 days (95% CI, 104-113). Most patients were treated with a standard split-course approach with initial pelvic radiation fields, then midcourse repeat transurethral resection of bladder tumor followed by bladder tumor bed boost fields, and 14/15 received concurrent chemotherapy. Alignment to fiducials could allow for reduced planning target volume margins (0.67 vs 1.56 cm) for the initial phase of RT, but not for the boost (1.01 vs 0.96 cm). This allowed for improved target coverage (D95% 80%-83% to 91%-94%) for 2 patients retrospectively planned with both volumetric-modulated arc therapy and 3-dimensional conformal RT. At median follow-up of 22 months, no acute or late complications attributable to TraceIT placement occurred. No patients required salvage cystectomy. ConclusionsTraceIT intravesical fiducial placement is safe and feasible and may facilitate tumor bed delineation and targeting in patients undergoing RT for localized muscle invasive bladder cancer. Improved image guided treatment may facilitate strategies to improve local control and minimize toxicity.

Definitive radiotherapy for squamous cell carcinoma of the oral cavity: a single-institution experience.

BackgroundSurgery is standard of care for oral cavity cancer (OCC). We provide a single-institution experience using definitive radiotherapy (RT) with or without concurrent systemic therapy for primary unresectable OCC.Patients and methodsWe retrospectively examined 49 patients with non-metastatic primary unresectable OCC treated with definitive RT between 2000 and 2019. The majority of patients (63.3%) were treated with definitive chemoradiotherapy while 26.5% were given single-agent cetuximab weekly simultaneous to definitive RT. Five patients were treated with definitive RT alone because of limited disease and no nodal involvement.ResultsMedian follow-up was 73 months (range, 6–236 months), median progression free survival (PFS) was 42 months (range, 2–157 months), median local disease-free survival (LDFS) was 44 months (range, 2–157 months) and median overall survival (OS) from the time of RT initiation was 52 months (range, 5–236 months). There were 65.3% locoregional failures, 84.4% local and 15.6% distant metastasis. The majority of patients with local failure presented with American Joint Committee on Cancer (AJCC) Stage III–IV disease (59.2%). The 5-year Kaplan-Meier estimates for OS (III–IV vs. I–II) was 22.8% vs. 54.2 % (p = 0.03, HR 2.090, 1.1–4.2). Patients who were treated with systemic therapy had a significant better 5-year overall survival compared to those with RT alone (43.9% vs. 23.1%, p = 0.05, 1.0–4.1). RT with doses less than 70 Gy (p = 0.046, HR 2.1 (1.0–4.5) was associated with worse overall survival. Mucositis was the most common ≥ grade 3 acute toxicity and occurred in 19 patients (39%). Incidences of chronic toxicities were loss of taste, trismus, osteoradionecrosis and xerostomia.ConclusionsDefinitive RT with or without concurrent systemic agents in patients with unresectable OCC resulted in an eloquent rate of locoregional control and good overall survival rates and is currently the best available treatment option in this patient collective.

Treatment outcomes of re-irradiation using stereotactic ablative radiotherapy to lung: a propensity score matching analysis

BackgroundThe purpose of this study was to compare the treatment efficacy and safety of re-irradiation (re-RT) using stereotactic ablative radiotherapy (SABR) and initial SABR for primary, recurrent lung cancer or metastatic lung tumor.MethodsA retrospective review of the medical records of 336 patients who underwent lung SABR was performed. Re-RT was defined as the overlap of the 70% isodose line of second-course SABR with that of the initial radiotherapy, and 20 patients were classified as the re-RT group. The median dose of re-RT using SABR was 54 Gy (range 48–60 Gy), and the median fraction number was 4 (range 4–6). One-to-three case-matched analysis with propensity score matching was used, and 60 patients were included in the initial SABR group of the matched cohort.ResultsThe 1- and 2-year local control rates for the re-RT group were 73.9% and 63.3% and those for the initial SABR group in the matched cohort were 92.9% and 87.7%, respectively (P = 0.013). There was no difference in distant metastasis-free, progression-free, and overall survival rates. The crude grade ≥ 2 toxicity rates were 40.0% for the re-RT group and 25.0% for the initial SABR group (P = 0.318). Re-RT group had higher acute grade ≥ 2 toxicity rates (25.0% vs 5.0%, P = 0.031). One incident of grade 3 toxicity (pulmonary) was reported in the re-RT group; there was no grade 4‒5 toxicity.ConclusionsThe local control rate of the in-field re-RT SABR was lower than that of the initial SABR without compromising the survival rates. The toxicity of re-RT using SABR was acceptable.

A prospective behavioral and imaging study exploring the impact on long-term memory of radiotherapy delivered for a brain tumor in childhood and adolescence

BackgroundPosterior fossa tumors represent two thirds of brain tumors in children. Although progress in treatment has improved survival rates over the past few years, long-term memory impairments in survivors are frequent and have an impact on academic achievement. The hippocampi, cerebellum and cerebellar-cortical networks play a role in several memory systems. They are affected not only by the location of the tumor itself and its surgical removal, but also by the supratentorial effects of complementary treatments, particularly radiotherapy. The IMPALA study will investigate the impact of irradiation doses on brain structures involved in memory, especially the hippocampi and cerebellum. Methods/designIn this single-center prospective behavioral and neuro-imaging study, 90 participants will be enrolled in three groups. The first two groups will include patients who underwent surgery for a posterior fossa brain tumor in childhood, who are considered to be cured, and who completed treatment at least 5 years earlier, either with radiotherapy (aggressive brain tumor; Group 1) or without (low-grade brain tumor; Group 2). Group 3 will include control participants matched with Group 1 for age, sex, and handedness. All participants will perform an extensive battery of neuropsychological tests, including an assessment of the main memory systems, and undergo multimodal 3 T MRI. The irradiation dose to the different brain structures involved in memory will be collected from the initial radiotherapy dosimetry. DiscussionThis study will provide long-term neuropsychological data about four different memory systems (working memory, episodic memory, semantic memory, and procedural memory) and the cognitive functions (attention, language, executive functions) that can interfere with them, in order to better characterize memory deficits among the survivors of brain tumors. We will investigate the correlations between neuropsychological and neuroimaging data on the structural (3DT1), microstructural (DTI), functional (rs-fMRI), vascular (ASL) and metabolic (spectroscopy) impact of the tumor and irradiation dose. This study will thus inform the setting of dose constraints to spare regions linked to the development of cognitive and memory functions. Trial registrationClinicalTrials.gov: NCT04324450, registered March 27, 2020, updated January 25th, 2021. Retrospectively registered, https://www.clinicaltrials.gov/ct2/show/NCT04324450.