Pre Radiotherapy Research Articles

Fully automated 3D body composition analysis and its association with overall survival in head and neck squamous cell carcinoma patients.

We developed a method for a fully automated deep-learning segmentation of tissues to investigate if 3D body composition measurements are significant for survival of Head and Neck Squamous Cell Carcinoma (HNSCC) patients. 3D segmentation of tissues including spine, spine muscles, abdominal muscles, subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and internal organs within volumetric region limited by L1 and L5 levels was accomplished using deep convolutional segmentation architecture - U-net implemented in a nnUnet framework. It was trained on separate dataset of 560 single-channel CT slices and used for 3D segmentation of pre-radiotherapy (Pre-RT) and post-radiotherapy (Post-RT) whole body PET/CT or abdominal CT scans of 215 HNSCC patients. Percentages of tissues were used for overall survival analysis using Cox proportional hazard (PH) model. Our deep learning model successfully segmented all mentioned tissues with Dice's coefficient exceeding 0.95. The 3D measurements including difference between Pre-RT and post-RT abdomen and spine muscles percentage, difference between Pre-RT and post-RT VAT percentage and sum of Pre-RT abdomen and spine muscles percentage together with BMI and Cancer Site were selected and significant at the level of 5% for the overall survival. Aside from Cancer Site, the lowest hazard ratio (HR) value (HR, 0.7527; 95% CI, 0.6487-0.8735; p = 0.000183) was observed for the difference between Pre-RT and post-RT abdomen and spine muscles percentage. Fully automated 3D quantitative measurements of body composition are significant for overall survival in Head and Neck Squamous Cell Carcinoma patients.

Dental assessment pre radiotherapy for head and neck cancer

Statement of the problem Head and neck cancer (HNC) and its treatment can dramatically change a patient’s appearance, speech, and oral function. Radiotherapy (RT) as a primary or adjuvant management strategy can result in osteoradionecrosis (ORN), salivary gland hypofunction, and can contribute to dental caries, among other sequelae. Assessment by a dentist prior to RT is important to remove suspect teeth in the field of radiation and commence preventive and restorative care for the long term. This can reduce subsequent ORN risk, reduce oral complaints during RT, and optimise oral health-related quality of life (OHRQoL). Purpose of the study This is a large-scale cohort study investigating dental treatment provided to a group undergoing RT for primary tumours of the head and neck. Materials and methods A retrospective chart review was carried out of all patients who had presented at the pre-RT dental clinic at Dublin Dental University Hospital from 2018 to 2019. Results A total of 490 patients were included. The mean age at presentation was 63 years (SD = 11). Approximately 50% of patients required removal of at least one unit and 12.7% of patients required basic dental restorations prior to commencement of RT. Most patients (93%) were assessed and treated within the requested timeframe. Conclusions Pre-RT assessment of HNC patients is important, as many require dental treatments such as extractions or basic restorations. Early planning for dental review should be considered to allow adequate time for assessment and proper treatment of long-standing dental issues.

1700P Radiation therapy elicits a consistent myeloid and lymphoid immune response in breast and rectal cancer

Radiotherapy (RT) is broadly used for cancer treatment, including early breast (eBRCA) and rectal cancers (RC). However, many components of the tumor microenvironment (TME) contribute to RT resistance. RT induces cancer cell death resulting in tumor antigen release that triggers the recruitment of a variety of immune cells that can act either stimulatory or suppressive on anti-tumor immunity. A deeper understanding of the immune suppressive components of anti-tumor immunity is integral to discover novel treatments to improve RT effectiveness. In this study, RT induced transcriptional changes were identified that associate with cellular consequences that may promote radio-resistance. Moreover, the delineation of tumor-specific changes can help selecting patients undergoing RT that are likely to have tumor recurrence. Datasets of patients with eBRCA (Horton 2015) and RC (Petty 2009) that received single-dose RT were analyzed. Gene signatures of immune activation and suppression were summarized for each patient as an average of the standard score and evaluated at the baseline and after RT. Fractions of immune cell populations were estimated by cell type deconvolution using xCell (Aran 2017) and compared pre and post RT. Evaluation of gene signatures of immune activation (inflammatory response, T-cell inflammation) and immune suppression (M2 macrophages, TGF-b signaling) in eBRCA and RC patients showed a consistent increase in pre compared to post RT. The comparison of score fold-change (pre-post RT) showed a stronger increase of the signatures in RC compared to eBRCA, with similar change for the TGF-b signaling score. Cell type deconvolution analysis showed that M1 and M2 macrophages and cancer-associated fibroblasts increase after RT in both tumor types, while NK T cells decrease. The main differences were found in neutrophils and regulatory T cells that have opposite trends in the two tumor types. The results showed an overall increase of immune activation and suppression genes after RT, more pronounced in RC compared to eBRCA patients. Moreover, the TME of RC showed a more immune-suppressive profile with an increase of regulatory T cells in addition to M2 macrophages.

Unilateral vs. Bilateral Radiotherapy for Oropharyngeal Carcinoma: Impact on Long Term Symptom Burden

<h3>Purpose/Objective(s)</h3> Bilateral neck radiotherapy (RT) is often required for oropharyngeal carcinoma (OPC) patients while unilateral neck RT is only used for selected small well-lateralized primary tonsillar tumors with no/minimal ipsilateral nodal disease. Our purpose is to compare long-term symptom burden following unilateral vs bilateral RT in patients with oropharyngeal carcinoma (OPC). <h3>Materials/Methods</h3> A retrospective review was conducted for patients with T1-3 N0-2b (AJCC 7th edition) tonsillar cancer treated with IMRT from 2011 to 2017. Patient-reported symptom burden was collected in routine practice using the MD Anderson Symptom Inventory (MDASI) at baseline, RT-end (3 weeks pre or post final RT fraction), 3 weeks – 3 months, 3 – 6 months, 6 – 12 months, 12 - 24 months, and 24 - 36 months post RT. Within each period, the latest record was chosen if there were multiple records available for one patient. MDASI symptom scores (ranging from 0 = "not present" to 10 = "as bad as you can imagine") were compared between unilateral vs bilateral RT groups at each time point using Wilcoxon Rank-Sum tests and linear mixed effect model. <h3>Results</h3> A total of 256 patients were eligible, of whom MDASI scores were available in 125 including 22 (18%) with unilateral and 103 (82%) with bilateral neck RT. Median age was 59 years, and 95 (76%) were male. The differences in "Dry Mouth" scores from baseline to 6 months and from baseline to 36 months were significantly better (lower) in the unilateral RT group on mixed effect model analysis [mean 2.11 (95% CI: 1.056 – 3.17) vs 3.72 (95% CI: 3.15 – 4.29), p = 0.004] and [mean 1.43 (95% CI: 0.44 - 2.42) vs 2.62 (95% CI: 2.1 - 3.13), p = 0.04] respectively; these differences meet a conventional threshold for clinical importance. MDASI change scores in other domains were similar between the two groups (all p > 0.05). Mean MDASI raw scores were highest at RT-end for all domains with improvement by 2 years for most symptoms. The unilateral RT group had significantly better (lower) raw MDASI scores in "Dry Mouth" at baseline (mean 0.3 vs 1.4, p = 0.045) and 6 months post RT (mean 2.6 vs 5.4, p <0.001). "Swallowing" raw scores were also statistically and clinically significantly better (lower) in the unilateral RT group at 6 months post-RT (mean 2.1 vs 3.5, p = 0.047). <h3>Conclusion</h3> Patients receiving unilateral RT fare better with "Dry mouth" by 6-month and 36-month and possibly with "Swallowing" by 6-month post RT compared to patients receiving bilateral RT.

Xerostomia quality of life and resource requirements following parotid sparing adaptive radiotherapy in head and neck cancers: Results of a prospective cohort study (Study ID CTRI/2017/11/010683)

Background and PurposeParotid sparing adaptive radiotherapy (PSART) is resource intensive to implement. Selection criteria for using ART and its impact on quality of life (QoL) is poorly reported. This has been addressed in our study. Materials and MethodsPatients planned for curative radiotherapy for Head Neck Cancers were recruited following informed consent in a prospective cohort study. PSART was planned if the mean dose to index parotid(s) increased by 2% from the baseline approved plan. To assess the resource requirements of PSART manpower and time required for treatment planning both for initial as well as PSART was documented. Patient reported QoL using QualiXeQLS and EORTC QLQ C30 and HN35 were obtained pre radiotherapy, and at 3 and 9 months post radiotherapy. ResultsOf the ninety patients accrued, 87 were evaluable. 45 (51%) received PSART based on the prespecified criteria. The average time spent in contouring (276 min versus 133 min) and treatment planning (293 min versus 108 min) were almost doubled when PSART was implemented. XeQoL scores at 3 months were significantly worse in those receiving PSART (mean 2.3 vs 1.2, p 0.002). Despite this, xerostomia related QoL recovered to near baseline scores by 9 months after receiving PSART. ConclusionImplementation of PSART is resource intensive. The proposed cutoff for implementing PSART identifies a higher risk population that have worse xerostomia related quality of life. This study lays the foundation for a randomized trial to determine the efficacy of PSART on xerostomia related QoL.

Comparison of rigid and deformable coregistration between mpMRI and CT images in radiotherapy of prostate bed cancer recurrence.

To evaluate the accuracy of rigid coregistration between multiparametric magnetic resonance (mpMR) and computed tomography (CT) images for radiotherapy of prostate bed cancer recurrence. Fifty-three patients (59 nodules) accrued in a prospective study on salvage radiotherapy for prostatic bed recurrence were suitable for the analysis. Patients underwent a pre radiotherapy mpMR exam and a planning CT in the same treatment position and with control of organ filling. The site of recurrence was delineated on mpMR images and contours transferred on planning CT images using both rigid and deformable registrations. Coregistrations were evaluated by mathematical operators that quantify deformation (Jacobian determinant and vector curl) and similarity indices (Dice and Jaccard coefficients). Dose coverage was evaluated. Deformable registration did not change volumes, (p=0.92MW test). The Jacobian coefficient and the vector curl revealed no important image deformations. Dice and Jaccard coefficients indicated dislocation of the nodule volumes. Dislocation magnitude was d=(5.6±3.1)mm. Organ filling was not correlated with deformation or dislocation. Volumes were covered by the 95% isodose in 96% of cases when rigid registration was performed versus 75% of cases when deformed. Rigid image coregistration is sufficiently accurate in this setting. The results indicate that the deformable registration tends to shrink the voxels and to dislocate the ROI, the adopted expansion for the recurrence volume adequately accounts for the observed deformation and dislocation, provided that organ filling is controlled.

Dental Care in Head and Neck Cancer Patients Undergoing Radiotherapy.

External beam radiotherapy is an integral part of the management of head and neck cancer. Radiotherapy for head and neck cancer lead to many treatment-related toxicities, including a wide range of dental morbidities. These complications depend on the various patient and treatment-related factors. Patients with poor oral hygiene, pre-existing periodontal disease, and the conventional mode of radiotherapy delivery are major factors leading to acute and severe late dental problems. Most of the complications are preventable with proper oral and dental care before, during and after radiotherapy. Pre radiotherapy dental evaluation to diagnose patients with potential risk and timely intervention can reduce long-term morbidities like carries, osteoradionecrosis, etc., thereby improving patients' quality of life. This article highlights the various aspects of dental care and management in head neck cancer patients before, during and after radiation therapy.

Lymphopenia in Pediatric Patients Following Proton Radiotherapy

Lymphopenia in Pediatric Patients Following Proton Radiotherapy

Predictive value of early evolution of plasma fibrinogen after breast cancer radiotherapy in detecting subclinical left ventricular dysfunction (BACCARAT study)

Breast cancer (BC) radiotherapy (RT) and resulting left ventricle (LV) exposure have been associated with subclinical LV dysfunction characterized by a global longitudinal strain (GLS) reduction > 10-15% that could arise 6 months after RT. The acute phase of radiation response consists of inflammatory process. Fibrinogen, an essential coagulation factor which has also important role in inflammatory response, may be useful to enhance prediction of the risk of subclinical LV dysfunction in BC patients treated with RT. To investigate the predictive value of pre-RT/post-RT plasma fibrinogen evolution in detecting patients with subclinical LV dysfunction defined as a GLS reduction > 10% six months after BC RT. The study consisted of BC patients treated with RT without chemotherapy. Speckle tracking echocardiography provided GLS before RT and 6 months postRT. Fibrinogen level was measured pre RT and at the end of RT and its evolution was defined by the ratio Post-RT-Pre-RT/Pre-RT (evoFIB). The prediction model was based on logistic regression including LV dose, evoFIB, and covariates. Area Under the Curve (AUC), sensitivity (Se), specificity (Spe) and misclassification error rate were considered in order to evaluate the predictive value of models. The study included 75 BC patients. The addition of FIB, to LV dose and covariates, in the prediction model, allowed enhancing the AUC from 0.80 to 0.85 with an OR per 10% evoFIB increase of = 1.60 (1.1–2.2). Se and Spe were increased from 67% to 75% and from 74% to 78% respectively. Information on evoFIB allowed decreasing misclassification error rate from 29% to 23%. Collecting information on fibrinogen level pre and post RT in BC patients treated with RT could help to enhance prediction of subclinical LV dysfunction. The inflammatory process associated with coagulation in the acute phase post-RT may also be involved in mechanism of cardiac dysfunction observed at later phase.

Evaluation of Neutrophil, Lymphocyte, Platelet, Mean Platelet Volume, Neutrophil-Lymphocyte Ratio, and Platelet-Lymphocyte Ratio in Prostate Cancer Patients Treated with Radiotherapy

Objective: Radiotherapy is a one cura­tive method for prostate cancer. Ionizing radiation can cause inflammation of tissues in and around the irradiated sites. But it is also suggested that low-dose radiation has anti-inflammatory effects. The present study was aimed at investigating the effects of radiotherapy on some inflammatory markers in prostate cancer patients.&#x0D; Material and Methods: A total of 42 patients with prostate cancer and 30 healthy subjects were included in the present study. The day prior to radiotherapy (pre radiotherapy group) and the day radiotherapy was completed (post radiotherapy group) venous blood samples were collected. Neutrophil, lymphocyte, platelet, mean platelet volume (MPV), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) levels were detected.&#x0D; Results: Neutrophil values of the pre radiotherapy group were higher than the control group (p&lt;0.05), and values of the post radiotherapy group were lower than the pre radiotherapy group (p&lt;0.001). Lymphocyte values of the post radiotherapy group were lower than the control, and the pre radiotherapy groups (p &lt;0.001 for both). Platelet values were decreased in the post radiotherapy group compared to the pre radiotherapy group (p &lt;0.01). MPV values of the pre radiotherapy group were higher than the control group (p&lt;0.05), and were lower in the post radiotherapy group than the pre radiotherapy group (p &lt;0.001). NLR and PLR values were decreased in the post radiotherapy group compared to the control group (p &lt;0.001 for both), and were increased in post radiotherapy group compared to the pre radiotherapy group (p&lt;0.001 for both).&#x0D; Conclusion: Our findings showed that neutrophil, and MPV were increased in the pre radiotherapy group compared to the control group. Neutrophil, lymphocyte, platelet, and MPV were decreased, NLR and PLR were increased in the post radiotherapy group compared to the pre radiotherapy group.

Abstract OT2-03-01: A phase one trial of olaparib with radiation therapy in patients with triple negative breast cancer: RADIOPARP

Abstract Background Preclinical studies have shown that breast cancer (BC) cell lines with a triple-negative phenotype are more sensitive to PARP1 inhibitors compared with non-TNBC cells. All these lines of evidence provide a strong rationale for developing a new therapeutic approach to TNBC based on targeting the DNA-repair defects via PARP inhibition in TNBC. Research hypothesis for patients with inoperable TNBC, there is a lack of systemic therapy to combine with radiotherapy (RT) in order to control the loco-regional disease. For patients with TNBC operated with residual disease (after neoadjuvant chemotherapy), a new strategy with postoperative RT in combination with new drugs could improve loco regional outcome. Rational for the study is the radiosensitization by olaparib in TNBC. The aim of the proposed phase I study is to determine the Maximal Tolerated Dose (MTD) of olaparib monotherapy administered with concurrent loco regional radiotherapy in patients who have TNBC inoperable after neoadjuvant chemotherapy or with residual disease after surgery. Primary objective: To determine the Maximal Tolerated Dose (MTD) of olaparib administered with concurrent RT in patients with TNBC. Secondary objectives • To assess the safety profile of concurrent olaparib-RT; evaluate efficacy profile and patient outcome, explore biomarkers of concurrent olaparib-RT activity. Study Overview: olaparib (orally, tablets) is administered at a starting dose of 50 mg bid. The other dose levels are: 50mg-100 mg - 150 mg-200 mg bid. Seven days prior to their first fraction of RT, patients will start olaparib at the assigned dose twice daily each day. All patients will receive RT on day 8 after the start of olaparib as following: normofractionated radiotherapy to whole breast or chest wall with or without the lymph node areas (LN). Patients will be assigned to olaparib one week before RT and during breast radiation (5 to 6 weeks). Total treatment duration will be: 6 to 7 weeks. Eligibility Women aged &amp;gt;18 years. With histologically confirmed TNBC with indication for pre or post-operative or exclusive RT; ECOG &amp;lt;2; Life expectancy &amp;gt; 6 months; Adequate hematologic, renal and hepatic function; Urine or serum negative pregnancy test; Ability to swallow and retain oral medications and affiliated to the French Social Security System. Sample size and Analysis: Phase I dose-finding based on toxicity will be conducted in a sequential and adaptive Bayesian scheme, using the method of Time-to-event Continual Reassessment Method to determine the Maximum Tolerated Dose (MTD) of olaparib associated with radiotherapy. The primary endpoint is Dose-Limiting Toxicity (DLT) occurring within 4-6 weeks after the end of the radiotherapy (12 or 13 weeks from the first drug intake, depending on the period of RT length). Dose allocation will be centrally defined, based on DLT observed in all patients previously evaluated, by modeling the probability of DLT. An empiric model will be used for the dose-toxicity relationship. No intra-patient dose-escalation is permitted. The MTD is defined as the dose associated with 25% of DLT. Four dose levels are considered as previously described. Cohort of size 3 is used with the TITE-CRM design. So, three patients will be included at the first dose level (50mg bid daily). At least three patients fully observed are required at a given dose level before dose escalation following the TITE-CRM method. Every new patient will be treated at the best current recommended dose proceed (50mg bid, 100mg bid, 150mg bid and 200mg bid daily), i.e. the dose associated with an estimated level of toxicity that is judged acceptable (25% DLT). Twenty-four to 30 patients are expected to be enrolled. Contact: youlia.kirova@curie.fr Acknowledgements: AstraZeneca for their support Citation Format: Youlia M. Kirova, Delphine Loirat, Frederique Berger, Manuel Rodrigues, Louis Bazire, Anne Chilles, Jean Yves Pierga, Francesco Ricci, Marie Paule Sablin, Anne Vincent Salomon, Fatima Laki, Claire Bertrand, Cyrine Ezzili, Laurence Raizoville, Veronique Mosseri, Souhir Neffati, Monia Ezzalfani, Alain Fourquet. A phase one trial of olaparib with radiation therapy in patients with triple negative breast cancer: RADIOPARP [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT2-03-01.

Is Radiotherapy Adequate Treatment for Patients not in Complete Metabolic Response after First-Line Chemotherapy for DLBCL?

Failure to achieve complete metabolic response (CMR) on 18-FDG PET/CT at the end of chemotherapy (CT) in diffuse large B cell lymphoma (DLBCL) is associated with poor prognosis. Patients (pts) are usually considered for salvage CT and autologous stem cell transplant if fit. However salvage often fails and is not suitable for a substantial proportion of pts. A subset of these pts have localised uptake that can be treated with radiotherapy (RT) but the efficacy of RT in this situation is not established. This study aims to assess the efficacy of salvage RT after incomplete response to first line CT and identify factors that may predict its efficacy. We performed a retrospective review of DLBCL pts who had residual FDG uptake on PET/CT after first line CT and subsequently received RT. Eligibility included: treatment with curative intent, RCHOP or similar, post-CT PET/CT Deauville score (DS) 4 - 5, RT ≥30Gy within 8 weeks. End points included: relapse rate, pattern of relapse, response to RT and overall survival (OS). We included 44 pts treated March 2011-August 2018 with median follow up (FU) of 29.3 months (1.6-90.8). Table 1 shows pt, disease and treatment characteristics. 45.5% were stage 3-4. 88.7% received RCHOP/RminiCHOP with median of 6 cycles. DS was 4 and 5 in 77.3% and 22.7%. During FU 14 (31.8%) pts relapsed/progressed. 10 (71.4%) relapsed outside the RT volume, 1 (7.1%) inside and 3 (21.4%) relapsed in both. Progression occurred relatively early with a median time from RT of 4.0 months (0.8-51). Of those who relapsed, 6 received salvage CT and 3 are alive with median FU of 50.8 months (26.9-90.7). 13 pts died, 11 of lymphoma and 2 of unrelated causes. Median OS is 75 months (1.6-90.8). PET/CT scans were performed after RT in 40/44 (90.9%) of pts. Half achieved CMR, 10 had DS 4 and 10 DS 5. The risk of relapse was related to the post RT PET status. 9/10 (90%) of pts with DS5 relapsed compared to 1/10 (10%) with DS4 and 4/20 (20%) of pts with CMR. Relapse risk was also related to the pre RT DS. Relapse occurred in 5/10 (50%) pts with DS 5 compared to 9/34 (26.5%) with DS 4. There was no difference in relapse rate according to RT dose (30/30.6 vs ≥36Gy). RT seems to be an adequate treatment for a substantial proportion of pts not achieving CMR following initial CT with more than half remaining in long term remission. Pts with post CT DS 4 had a better outcome after RT.Abstract 139; Table 1Patient and treatment characteristics Male Femalen (%) 22 (50) 22 (50)Median Age /years (range)65.5 (21-89)Histopathology Germinal centre (GC) Non GC THRLB-CL PMBCL NOS16 (36.3) 10 (22.7) 2 (4.5) 6 (13.6) 10 (22.7)Stage 1 2 3-44 (9.1) 20 (45.5) 20 (45.5)IPI 0-1 2 3 4-516 (36.4) 11 (25) 9 (20.5) 8 (18.2)Median no of cycles (range) R miniCHOP RCHOP/RCEOP RGCVP/RCVP COPADM-R6 (3-8) 9 (20.5) 31 (70.5) 3 (6.8) 1 (2.3)End of CT DS 4 534 (77.3) 10 (22.7)RT dose (Gy) 30/30.6 36 4017 (38.6) 18 (40.9) 9 (20.5) Open table in a new tab

Incidence of Otitis Media with Effusion in Cases of Head and Neck Malignancies Undergoing Radiotherapy: A Prospective Observational Study.

This study was done to evaluate the incidence of otitis media with effusion (OME) in cases of head and neck malignancies who undergo irradiation, excluding nasopharyngeal malignancies. This prospective observational study was done at a tertiary care hospital. Adult patients of head and neck malignancies treated with radiotherapy (RT) with or without concurrent chemotherapy as definitive or adjuvant therapy from September 2017 to August 2018 were included. Cases of nasopharyngeal malignancies and cases of malignancies of other sites extending to nasopharynx causing mechanical obstruction to ET were excluded. The otoscopy, tympanometry and pure tone audiometry findings of these patients were recorded pre RT, immediately after completion of RT and at 6months post RT. The pre and post RT data were analysed to determine the incidence of OME. 39.3% of ears had retracted tympanic membrane (TM) and 7.1% had air-fluid levels in middle ear at first follow up (FFU). At second follow up (SFU), 13% of ears continued to have retracted TM while none had air-fluid levels. At FFU, 23.2% of ears had 'B' curve on tympanometry, indicative of OME while 19.6% of ears had 'C' curve, indicative of Eustachian tube (ET) dysfunction. At SFU, 1.8% had B curve while 14.3% had C curve, indicating improvement in ET function as compared to that at FFU. There is a considerable percentage of non-nasopharyngeal head and neck malignancy cases who develop OME post RT, however, in most of them it resolves spontaneously.

PD25-10 ESTIMATION OF THE RISK OF MISSING ADVERSE PATHOLOGICAL PROSTATE CANCER FEATURES AFTER SALVAGE RADICAL PROSTATECTOMY IN PATIENTS ELIGIBLE FOR FOCAL SALVAGE THERAPIES

INTRODUCTION AND OBJECTIVES:Focal salvage therapies (FST) for locally recurrence prostate cancer (PCa) after primary radiotherapy (RT) can reduce the risk of adverse events associated with salvage radical prostatectomy (sRP) while maintaining cancer control, in selected patients. However, the risk of missing adverse PCa features undergoing FST instead of sRP has never been investigated. We aimed to assess the rates and predictors of adverse PCa features in patients eligible for FST who ultimately underwent sRP.METHODS:We reviewed 120 patients with locally recurrent PCa after RT who underwent sRP and extended pelvic lymph node dissection (2000-2016). Metastatic disease was excluded by choline PET and bone scan. Pre RT PSA, clinical stage (cT), biopsy Gleason score (GS) prior to RT and prior to sRP, PSA nadir, PSA prior to surgery, and pathohistology of sRP specimens were analysed. Eligibility criteria for FST were based on EAU Guidelines: cT1-cT2 PCa, initial GS ≤7 and pre-salvage PSA <10 ng/mL. Adverse fe...

Observed high incidence of prostatic calculi with the potential to act as natural fiducials for prostate image guided radiotherapy

This study aims to quantify the incidence and distribution of prostatic calculi in a population of prostate radiotherapy patients and assess their potential role in prostate image guided radiotherapy (IGRT). A retrospective analysis of trans-rectal ultrasound (TRUS), computed tomography (CT) planning and treatment verification cone beam CT (CBCT) scans from radical prostate radiotherapy patients (external beam and brachytherapy) between 2012 and 2014 was undertaken by a single experienced observer. An internationally validated schema from the Prostate Imaging Reporting and Data system (PIRADS) was used to map the location of calculi. The association of calculi with patient and disease characteristics was explored. Data was analysed using SPSS (IBM version 22.0) using descriptive statistical methods and logistic binary regression analysis. 389 scan sets from 254 patients were included in the analysis. The overall incidence of calculi was 85% (n = 218) of which 79% (n = 201) were intra-prostatic calculi. The mean number of intra-prostatic calculi was 2 (range 1-10) and the mean size of calculi was 3.7 mm (range 0.5-15 mm). Calculi were most frequently observed in the posterior of the mid-gland (PI-RADs 3p, 9p) and posterior of the apex (PI-RADs 5p, 11p). 99% (n = 135) of CT planning scans with a corresponding CBCT had calculi in the same PIRADs location and all calculi were visible at the last fraction. There was no statistically significant association of calculi and N stage, M stage or Gleason score. A significant proportion of prostate radiotherapy patients have prostatic calculi detectable on pre radiotherapy imaging. Calculi observed on CT were also detectable on CBCT in 99% of cases and remain visible at the end of treatment. These findings add to the growing evidence base supporting the potential of calculi as an alternative to fiducial markers to aid prostate IGRT.

Hearing morbidity post head and neck radiotherapy

Introduction: radiation therapy carries an important role in the treatment of head and neck (H&amp;N) cancers. Exposure of cells to ionizing radiation produces a variety of biological and molecular changes that may manifest clinically as tumor killing or normal tissue toxicity, the type and severity of these effects depend on variables such as the energy and type of radiation, the composition of target biologic tissue, the cellular and molecular response, duration of exposure, and cellular microenvironment. A sound signal in the environment is collected by the pinna, passes through external auditory canal and strikes the tympanic membrane_ Vibrations of the tympanic membrane are transmitted to stapes footplate through a chain of ossicles coupled to the tympanic membrane Movements of stapes footplate cause pressure changes in the labyrinthine flu ids which move the basilar membrane. This stimulates the hair cells of the organ of Corti. It is these hair cells which act as transducers and convert the mechanical energy into electrical impulses which travel along the auditory nerve.&#x0D; Objective: to determine the effect of radiotherapy on hearing process.&#x0D; Method: Prospective case control study on 45 patients (90 ears) in al diwaniyah teaching hospital from January 2013 to October 2016 with head and neck malignant tumors diagnosed by histopathological specimens, of both sexes and treated with radiotherapy are included in the study. Patient with history of hearing impairment (disabling or documented sever to profound hearing loss), chronic otitis media and those who receive chemotherapy previously are excluded from study. Pre radiotherapy pure tone audiogram and 6 month after when the patient come back to oncology unit for fellow up their condition those patients allocated in group A while group B (control) 45 healthy person (90 ears) are chosen from staff of hospital and college of medicine after announcement for volunteers in study pure tone audiogram done for them as in case group.&#x0D; Results: Regarding the mean of age for group A was 53 years with range from 30-70 years , with male: female ratio 4:1while for control group(B) was 49 years with range 25-60 years and male to female ratio 2:1. Most common neoplasia was carcinoma of larynx followed by nasopharyngeal , oropharyngeal and hypo pharyngeal carcinoma, oral cavity and paranasal sinuses Regarding hearing about 38 (42.18%) of patients (group A) not affected by radiotherapy while 43 patients (47.75%) got worse hearing after radiotherapy, only 9 patients (9.99%) had hearing improvement. While in control group 73 (81.11%) not changed, 6(6.66%) deteriorate and 11(12.22%) had improve hearing.&#x0D; Conclusions:&#x0D; &#x0D; Radiotherapy induced hearing problems occur in significant number in patient with head and neck tumors.&#x0D; Hearing morbidity post radiotherapy mainly sensory neural&#x0D; Patient counselling before radiotherapy about hearing disabilities should be regarded.&#x0D; Further long term studies and larger sample are needed.&#x0D;

Changes in Cardiac MRI Derived Left Ventricular Segmental Strain in Left Sided Breast Cancer Patients Treated with Tangential Radioation Therapy Alone Correlated with Dose

Reduction in left ventricular global and segmental myocardial strain following tangential radiotherapy (RT) for left sided breast cancer treatment has been demonstrated using advanced echocardiographic techniques. This study aimed to determine if cardiac MRI (CMR), a more sensitive and precise imaging modality, could detect similar changes in segmental myocardial strain as per the American Heart Association(AHA) 16 segment model of the left ventricle in left sided breast cancer patients, and correlate this to RT dose. For 21 patients receiving left-sided breast RT, two serial CMR scans were obtained; immediately prior, and 4-6 weeks following RT. Single breath-hold Steady-State Free Precession (SSFP) Cine 2, 3, 4 chamber and short axis views were acquired, and using cvi42 tissue tracking software, two independent readings of 2D and 3D strain values were obtained, with the average being used for analysis. A linear mixed effects model was used to account for potential clustering of values between patients and segments. Multiple RT dosimetric values (including mean, max, V25) of each segment were calculated and their relationship with delta 2D/3D strain values explored. Median age was 59 years (range 38-76 years). Comprehensive nodal treatment using modified wide tangents using a deep inspiration breath hold technique (n=1) and the remainder received tangential breast radiation alone (n=20). No patient received chemotherapy. Two patients received 50Gy in 25 fractions, with 19/21 receiving 42.4Gy in 16 fractions. Median mean heart dose was 2.6Gy (1.5-3.9Gy). No difference was found between any pre and post RT strain parameters. These results are summarised in the table below.Abstract TU_12_3436: Table 1Strain ParameterPre-RT MeanPost-RT MeanDifference95% CIRadial 2D (Short Axis)54.5950.23-3.43[-8.8, 1.9]Circumference 2D (Short Axis)-23.11-22.150.73[-0.51, 2.0]Radial 2D (Long Axis)48.5647.460.07[-3.7, 3.8]Longitudinal 2D (Long Axis)-22.45-22.27-0.08[-0.80, 0.63]Radial 3D40.7737.85-2.17[-7.4, 3.1]Circumference 3D-20.05-19.200.72[-0.62, 2.1]Longitudinal 3D-19.49-18.920.47[-0.79, 1.7]Note the calculated differences are modelled quantities taking into account patients as a random effect and missing data. Therefore values in Difference column are not equal to pre RT mean minus post RT mean. When correlated with several radiation measures, there were no significant relationships between any radiation parameters and change in serial strain. Open table in a new tab Note the calculated differences are modelled quantities taking into account patients as a random effect and missing data. Therefore values in Difference column are not equal to pre RT mean minus post RT mean. When correlated with several radiation measures, there were no significant relationships between any radiation parameters and change in serial strain. No differences in left ventricular segmental strain were detected using CMR 4-6 weeks following left-sided breast radiotherapy, nor was there a clear relationship between RT dose and delta strain. Changes below the threshold of CMR detection given the lower temporal scanning resolution of CMR cannot be excluded. Longer term follow-up of this cohort will help determine if more delayed effects of radiation on LV function become manifest.

Hearing morbidity post head and neck radiotherapy

Radiation therapy carries an important role in the treatment of head and neck (H&amp;N) cancers. Exposure of cells to ionizing radiation produces a variety of biological and molecular changes that may manifest clinically as tumor killing or normal tissue toxicity,the type and severity of these effects depend on variables such as the energy and type of radiation,the composition of target biologic tissue,the cellular and molecular response,duration of exposure,and cellular microenvironment.A sound signal in the environment is collected by the pinna,passes through external auditory canal and strikes the tympanic membrane_ Vibrations of the tympanic membrane are transmitted to stapes footplate through a chain of ossicles coupled to the tympanic membrane Movements of stapes footplate cause pressure changes in the labyrinthine flu ids which move the basilar membrane. This stimulates the hair cells of the organ of Corti. It is these hair cells which act as transducers and convert the mechanical energy into electrical impulses which travel along the auditory nerve.to determine the effect of radiotherapy on hearing process.Prospective case control study on 45 patients (90 ears) in Al diwaniyah teaching hospital from January 2013 to October 2016 with head and neck malignant tumors diagnosed by histopathological specimens,of both sexes and treated with radiotherapy are included in the study. Patient with history of hearing impairment (disabling or documented sever to profound hearing loss),chronic otitis media and those who receive chemotherapy previously are excluded from study. Pre radiotherapy pure tone audiogram and 6 month after when the patient come back to oncology unit for fellow up their condition those patients allocated in group A while group B (control) 45 healthy person (90 ears) are chosen from staff of hospital and college of medicine after announcement for volunteers in study pure tone audiogram done for them as in case group.Regarding the mean of age for group A was 53 years with range from 30-70 years, with male: female ratio 4:1while for control group (B) was 49 years with range 25-60 yearsand male to female ratio 2:1. Most common neoplasia was carcinoma of larynx followed by nasopharyngeal, oropharyngeal and hypo pharyngeal carcinoma,oral cavity and paranasal sinuses Regarding hearing about 38 (42.18%) of patients (group A) not affected by radiotherapy while 43 patients (47.75%) got worse hearing after radiotherapy,only 9 patients (9.99%) had hearing improvement. While in control group 73 (81.11%) not changed,6 (6.66%) deteriorate and 11 (12.22%) had improved hearing.Radiotherapy induced hearing problems occur in significant number in patient with head and neck tumors.Hearing morbidity post radiotherapy mainly sensory neural. Patient counselling before radiotherapy about hearing disabilities should be regarded. Further long term studies and larger sample are needed.

Treatment Outcomes of Chemoradiation in Anaplastic Gliomas

Gliomas account for 80% of primary malignant brain tumors. Standard treatment for grade III gliomas is surgical resection followed by radiotherapy (RT). Evidence for concurrent and adjuvant chemotherapy is not as robust as for Glioblastoma. The aim of the study was to analyze the clinical profile and survival of patients with anaplastic gliomas treated at our institute. A retrospective analysis of patients with histopathological diagnosis of anaplastic gliomas from January 2010 to December 2015 was done from the treatment and follow up records. Patients had undergone maximal safe resection and had received postoperative radiotherapy (60 Gy) with or without concurrent and adjuvant temozolomide. Sub ventricular zone (SVZ) was also contoured along as 5 mm expansion along the lateral margin of the lateral ventricles on axial planning CT fused with MRI. Dosimetric data was collected from the treatment planning system. Statistical analysis was done using SPSS 20 software. A total of 88 patients were included in the study. The median age was 35 years (range 6-68 yrs). 63% were males and 37% females with male: female ratio of 1.75:1. Most common presentation was with headache (61%), seizures (43%), vomiting (18%) or hemiparesis (18%). Out of 88 patients 72 patients received concurrent/adjuvant chemotherapy with temozolomide. Follow up records was available for 75 patients The 6 yr overall survival (OS) was 60%. Patients less than or equal to 35 years had OS of 71 months compared to 65 months for patients above 35 years. (Log rank p= 0.8). Patients having focal neurological deficit at presentation had OS of 65 months compared to 71 months in patients without focal neurological deficit. (Log rank p= 0.6). Surgical extent defined by operating surgeon did not correlate with survival. Patients with anaplastic oligodendroglioma histology had OS of 71 months compared to 53 months for anaplastic astrocytoma (log rank p= 0.5). Based on KPS scores pre radiotherapy, KPS <70 had a median OS of 16 months and KPS > 70 had an OS of 65 months. (Log rank p= 0.001) The mean and median dose of ipsilateral SVZ was 51 and 57.7 Gy respectively. Median survival had not yet reached in the subgroup of Gross total resection (GTR) patients who received an ipsilateral SVZ dose of 57 Gy or greater, compared to 30 months for patients receiving < 57 Gy (log rank p= 0.008). 21 patients had documented recurrence with average time to recurrence being 45 months. 14 patients had salvage surgery and two patients underwent only reirradiation. The average survival after recurrence was 12 months. The 6 year overall survival was 60%. Age >35 years, no neurological deficit at presentation, oligodendroglioma histology, KPS ≥ 70 and no recurrence had better overall survival. In a subset of population with gross total resection, SVZ dose of >57 Gy showed improvement in survival.

Correlation of Dose to Bone Marrow With Hematological Toxicity and MRI Based Estimation of Conversion of Active to Inactive Bone Marrow in Long Course Neo adjuvant Chemoradiation for Locally Advanced Rectal Cancer

Aims : To correlate the dose to bone marrow with the incidence and grade of hematological toxicity and to estimate the extent of inactivation of bone marrow in patients with locally advanced rectal cancer undergoing neo adjuvant long course chemoradiation. Methods and materials: 20 patients with locally advanced rectal cancer were enrolled for the study after clearance from the institution review board. All the patients received preoperative long course radiotherapy using 3D conformal modality to a dose of 50.4Gy.They received concurrent chemotherapy with daily Capecitabine (825mg/m2). The entire pelvis was contoured on the simulation CT, the active marrow (red) bone marrow was delineated on both the pre radiotherapy as well as the post radiotherapy MRI of the pelvis on the T1 weighted images. Baseline and weekly blood investigations were recorded during the course of therapy. The dosimetric parameters such as V5, V10, V20, V30 and V40 were correlated with the incidence of Grade 3 or more hematological toxicity. The pre and post radiotherapy volumes of the active marrow and the extent (in percentage volume) of inactivation of bone marrow (red to yellow marrow conversion) due to LCCRT was also documented. The Shapiro Wilk/Mann Whitney test was used to correlate the bone marrow dose with toxicities and the paired T test was used to test the significance of conversion of active to inactive marrow. Results: The incidence of grade 3 or more toxicity of hemoglobin correlated with V30 and V40 values(p value 0.02 and 0.0095 respectively). The toxicity grades of the other blood elements however did not show any correlation with any of the dosimetric variables. The median value of the pre radiotherapy active marrow was 346.21cc and the median of the post radiotherapy active marrow was 116.44cc.The percentage inactivation after therapy had a median value of 57.64% (range 38.98% - 83.39%)There was also a significant conversion of active to inactive bone marrow as detected on the MRI, the correlation of the pre and post neoadjuvant chemoradiotherapy marrow volumes was highly significant (p value <0.0001) Conclusion: The volume of pelvic bone marrow receiving at least 30Gy or more in patients undergoing long course chemoradiotherapy for locally advanced rectal cancer has a significant impact on anemia. There was also a significant conversion of active to inactive bone marrow as detected on the MRI. The significant myelosuppression associated with the use of both chemotherapy and radiotherapy in the management of rectal cancer warrants efforts to limit the toxicity to the bone marrow. The use of MRI and other functional imaging for visualization and delineation of the bone marrow and its use in radiotherapy planning is now providing possibilities to further limit normal tissue toxicity