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BACKGROUND AND PURPOSE Despite the excellent clinical outcomes from brachytherapy treatments compared with other modalities and the low associated costs, there have been reports of a decline in utilization of brachytherapy. The aim of this study was to investigate in detail the trend in utilization of brachytherapy in the province of Quebec, Canada, from 2011 to 2019. MATERIALS AND METHODS All radiotherapy clinics in the province of Quebec, and among these the clinics that provide brachytherapy treatments, were identified. This observational retrospective cohort study involved analysis of data compiled by the Ministere de la Sante et des Services Sociaux du Quebec for the period of 2011 to end of 2019 on all brachytherapy procedures performed in the province of Quebec. Time series graphs were used to describe the number of high dose rate (HDR) and low dose rate (LDR) brachytherapy treatments during the studied time period. Statistical analysis was conducted using R statistical software. RESULTS Between 2011 and 2019, 12 hospitals in the province of Quebec provided radiotherapy treatments, and all of them offered brachytherapy services. The median annual number of brachytherapy sessions was 4413 (range 3930-4829). HDR brachytherapy represented over 90% of all brachytherapy treatments throughout the study period. Significant changes over time were observed in the number of treatments: at least 5% change was seen only for the two most common subtypes of brachytherapy, HDR interstitial and HDR intracavitary, with an increase of 9.6% and a decrease of 9.2%, respectively. The use of other subtypes of brachytherapy (HDR-plesiotherapy, LDR-interstitial, LDR-intracavitary, LDR-eye plaque) was stable between 2011 and 2019, with ≤ 2.5% variation. CONCLUSION This study demonstrates an overall steady use of brachytherapy between 2011 and 2019 in Quebec. Brachytherapy offers numerous advantages for the treatment of diverse cancer sites. Although more sophisticated external beam radiotherapy treatments have emerged in the last decades, the precision and cost-effectiveness of brachytherapy remain unbeaten. To ensure the continued use and availability of brachytherapy, governments must put in place policies and regulations to that effect. Training and exposure of future health care professionals to brachytherapy within Quebec and Canada is essential to provide all patients the same access to this life saving modality.

Background Randomized studies have shown low compliance to adjuvant chemotherapy in rectal cancer patients receiving preoperative chemotherapy and external beam radiation (CT/EBRT) with total mesorectal excision. We hypothesize that giving neoadjuvant CT before local treatment would improve CT compliance. Methods Between 2010–2017, 180 patients were randomized (2:1) to either Arm A (AA) with FOLFOX x6 cycles prior to high dose rate brachytherapy (HDRBT) and surgery plus adjuvant FOLFOX x6 cycles, or Arm B (AB), with neoadjuvant HDRBT with surgery and adjuvant FOLFOX x12 cycles. The primary endpoint was CT compliance to ≥85% of full-dose CT for the first six cycles. Secondary endpoints were ypT0N0, five-year disease free survival (DFS), local control and overall survival (OS). Results Patients were randomized to either AA (n = 120, median age (MA) 62 years) or AB (n = 60, MA 63 years). 175/180 patients completed HDRBT as planned (97.2%). In AA, two patients expired during CT; three patients post-randomization received short course EBRT because of progression under CT (n = 2, AA) or personal preference (n = 1, AB). ypT0N0 was 31% in AA and 28% in AB (p = 0.7). CT Compliance was 80% in AA and 53% in AB (p = 0.0002). Acute G3/G4 toxicity was 35.8% in AA and 27.6% in AB (p = 0.23). With a median follow-up of 48.5 months (IQR 33–72), the five-year DFS was 72.3% with AA and 68.3% with AB (p = 0.74), the five-year OS 83.8% for AA and 82.2% for AB (p = 0.53), and the five-year local recurrence was 6.3% for AA and 5.8% for AB (p = 0.71). Conclusion We confirmed improved compliance to neoadjuvant CT in this study. Although there is no statistical difference in ypT0N0 rate, local recurrence, and DFS between the two arms, a trend towards favourable oncological outcomes is observed.

Background: Older cancer patients with locally advanced or metastatic disease may benefit from chemotherapy alone or combined with radiotherapy. However, chemotherapy is often omitted either because of physician bias or because of its underlying comorbidity, thus compromising their survival. The coronavirus disease 19 (COVID-19) pandemic is compounding this issue because of the fear of immunosuppression induced by chemotherapy on the elderly which makes them more vulnerable to the virus. Summary: Immunotherapy has less effect on the patient bone marrow compared to chemotherapy. The potential synergy between radiotherapy and immunotherapy may improve local control and survival for older patients with selected cancer. Preliminary data are encouraging because of better survival and local control in diseases which are traditionally resistant to radiotherapy and chemotherapy such as melanoma and renal cell carcinoma. Key Message: We propose a new paradigm combining immunotherapy at a reduced dose and/or extended dosing intervals and hypofractionated radiotherapy for older patients with selected cancer which needs to be tested in future clinical trials.

IntroductionLate gastro-intestinal toxicities (LGIT) secondary to pelvic radiotherapy (RT) are well described in the literature. LGIT are mainly related to rectal or ano-rectal irradiation; however, involvement of the anal canal (AC) in the occurrence of LGIT remains poorly described and understood.Materials and MethodsThe aim of this work was to explore the potential role of the AC in the development of LGIT after prostate irradiation and identify predictive factors that could be optimized in order to limit these toxicities. This narrative literature review was realized using the Pubmed database. We identified original articles published between June 1997 and July 2019, relating to LGIT after RT for localized prostate cancer and for which AC was identified independently. Articles defining the AC as part of an anorectal or rectal volume only were excluded.ResultsA history of abdominal surgery or cardio-vascular risk, anticoagulant or tobacco use, and the occurrence of acute GIT during RT increases the risk of LGIT. A dose-effect relationship was identified between dose to the AC and development of LGIT. Identification and contouring of the AC and adjacent anatomical structures (muscles or nerves) are justified to apply specific dose constraints. As a limitation, our review mainly considered on 3DCRT which is no longer the standard of care nowadays; we did not identify any reports in the literature using moderately hypofractionated RT for the prostate and AC specific dosimetry.ConclusionThese results suggest that the AC may have an important role in the development of LGIT after pelvic RT for prostate cancer. The individualization of the AC during planning should be recommended in prospective studies.

Purpose To investigate differences between prescribed and postimplant calculated dose in 192Ir high-dose-rate endorectal brachytherapy (HDR-EBT) by evaluating dose to clinical target volume (CTV) and organs at risk (OARs) calculated with a Monte Carlo–based dose calculation software, RapidBrachyMC. In addition, dose coverage, conformity, and homogeneity were compared among the radionuclides 192Ir, 75Se, and 169Yb for use in HDR-EBT. Methods and Materials Postimplant dosimetry was evaluated using 23 computed tomography (CT) images from patients treated with HDR-EBT using the 192Ir microSelectron v2 (Elekta AB, Stockholm, Sweden) source and the Intracavitary Mold Applicator Set (Elekta AB, Stockholm, Sweden), which is a flexible applicator capable of fitting a tungsten rod for OAR shielding. Four tissue segmentation schemes were evaluated: (1) TG-43 formalism, (2) materials and nominal densities assigned to contours of foreign objects, (3) materials and nominal densities assigned to contoured organs in addition to foreign objects, and (4) materials specified as in (3) but with voxel mass densities derived from CT Hounsfield units. Clinical plans optimized for 192Ir were used, with the results for 75Se and 169Yb normalized to the D90 of the 192Ir clinical plan. Results In comparison to segmentation scheme 4, TG-43–based dosimetry overestimates CTV D90 by 6% (P = .00003), rectum D50 by 24% (P = .00003), and pelvic bone D50 by 5% (P = .00003) for 192Ir. For 169Yb, CTV D90 is overestimated by 17% (P = .00003) and rectum D50 by 39% (P = .00003), and pelvic bone D50 is significantly underestimated by 27% (P = .007). Postimplant dosimetry calculations also showed that a 169Yb source would give 20% (P = .00003) lower rectum V60 and 17% (P = .00008) lower rectum D50. Conclusions Ignoring high-Z materials in dose calculation contributes to inaccuracies that may lead to suboptimal dose optimization and disagreement between prescribed and calculated dose. This is especially important for low-energy radionuclides. Our results also show that with future magnetic resonance imaging–based treatment planning, loss of CT density data will only affect calculated dose in nonbone OARs by 2% or less and bone OARs by 13% or less across all sources if material composition and nominal mass densities are correctly assigned.

Purpose We describe methods to improve dose delivery for patients with rectal cancer receiving boost brachytherapy after external beam radiotherapy. Methods and materials Patients with rectal cancer who were ineligible or refusing surgery are treated with external beam radiotherapy and subsequently with three weekly image-guided volume-adapted high-dose-rate brachytherapy boosts of 10 Gy to the residual clinical target volume, for a total of 30 Gy in three fractions. Tungsten shielding placed at the center of intracavitary mold applicator and double-balloon technique was used to improve dose conformity to the target. Results Our results show that the use of tungsten shield and double balloon reduces the dose gradient within the target volume to receive the prescription boost dose of 10 Gy from maximum dose of 60 Gy down to 20 Gy. Conclusions We outlined two methods for achieving higher high-dose-rate brachytherapy dose conformity using the tungsten shielding rods (to spare contralateral healthy tissues) and double-balloon technique (to decrease dose gradient within the target to minimize dose to the proximal mucosa).

The coronavirus disease 19 (COVID-19) pandemic is unprecedented as it reached all countries in the world within a record short period of time. Even though COVID-19 infection may be just severe in any adults, older adults (65-year-old or older) may experience a higher mortality rate. Among those affected, cancer patients may have a worse outcome compared to the general population because of their depressed immune status. As the health resources of most countries are limited, clinicians may face painful decisions about which patients to save if they require artificial ventilation. Cancer patients, especially the older ones, may be denied supportive care because of their shorter life expectancy. Thus, special considerations should be taken to prevent infection of older cancer patients and to provide them with adequate social support during their cancer treatment. The following proposal was reached: (1) Education of health care providers about the special needs of older cancer patients and their risks of infection. (2) Special consideration such as surgical masks and separate scheduling should be made to protect them from being infected. (3) Social services such as patient navigators should be provided to ensure adequate medical supply, food, and daily transportation to cancer centers. (4) Close monitoring through phone calls, telecommunication to ensure social distancing and psychological support from patient family to prevent anxiety and depression. (5) Shorter course of radiotherapy by use of hypofractionation where possible to decrease the needs for daily transportation and exposure to infection. (6) Enrollment of older cancer patients in clinical trials for potential antiviral medications if infection does occur. (7) Home health care telemedicine may be an effective strategy for older cancer patients with COVID-19 infection to avoid hospital admission when health care resources become restricted. (8) For selected patients, immunotherapy and targeted therapy may become the systemic therapy of choice for older cancer patients and need to be tested in clinical trials.

Neoadjuvant pelvic radiotherapy is widely used for patients with advanced rectal cancer. The trade-off between dose and response is well-established, yet little consensus remains on the precise methods of delivery and doses given in different scenarios. Professor Vuong reviews the evidence base and trial evidence on the escalation of radiotherapy dose and the methods of achieving this.

background: Pathological extramural vascular invasion (EMVI) is an independent prognostic factor in rectal cancer, but can also be identified on MRI-detected extramural vascular invasion (mrEMVI). We perform a meta-analysis to determine the risk of metastatic disease at presentation and after surgery in mrEMVI-positive patients compared with negative tumours. methods: Electronic databases were searched from January 1980 to March 2016. Conventional meta-analytical techniques were used to provide a summative outcome. Quality assessment of the studies was performed. results: Six articles reported on mrEMVI in 1262 patients. There were 403 patients in the mrEMVI-positive group and 859 patients in the mrEMVI-negative group. The combined prevalence of mrEMVI-positive tumours was 0.346(range=0.198–0.574). Patients with mrEMVI-positive tumours presented more frequently with metastases compared to mrEMVI-negative tumours (fixed effects model: odds ratio (OR)=5.68, 95% confidence interval (CI) (3.75, 8.61), z=8.21, df=2, P

Purpose Several radionuclides with high (60Co, 75Se) and intermediate (169Yb, 153Gd) energies have been investigated as alternatives to 192Ir for high-dose-rate brachytherapy. The purpose of this study was to evaluate the impact of tissue heterogeneities for these five high- to intermediate-energy sources in prostate and head & neck brachytherapy. Methods and Materials Treatment plans were generated for a cohort of prostate (n = 10) and oral tongue (n = 10) patients. Dose calculations were performed using RapidBrachyMCTPS, an in-house Geant4-based Monte Carlo treatment planning system. Treatment plans were simulated using 60Co, 192Ir, 75Se, 169Yb, and 153Gd as the active core of the microSelectron v2 source. Two dose calculation scenarios were presented: (1) dose to water in water (Dw,w), and (2) dose to medium in medium (Dm,m). Results Dw,w overestimates planning target volume coverage compared with Dm,m, regardless of photon energy. The average planning target volume D90 reduction was ∼1% for high-energy sources, whereas larger differences were observed for intermediate-energy sources (1%–2% for prostate and 4%–7% for oral tongue). Dose differences were not clinically relevant ( Conclusions Dw,w underestimates the dose to bones and, to a lesser extent, overestimates the dose to soft tissues for radionuclides with average energies lower than 192Ir. Further studies regarding bone toxicities are needed before intermediate-energy sources can be adopted in cases where bones are in close vicinity to the tumor.

Anal squamous cell carcinoma (ASCC) is an uncommon yet rising cancer worldwide. Definitive chemo-radiation (CRT) remains the best curative treatment option for non-metastatic cases in terms of local control, recurrence-free and progression-free survival. Still, despite overall good results, with 80% five-year survival, a subgroup of ASCC patients displays a high level of locoregional and/or metastatic recurrence rates, up to 35%, and may benefit from a more aggressive strategy. Beyond initial staging, there is no reliable marker to predict recurrence following CRT. Imaging, mostly positron emission tomography-computed tomography (PET-CT) and magnetic resonance imaging (MRI), bears an important role in the diagnosis and follow-up of ASCC. The routine use of radiomics may enhance the quality of information derived from these modalities. It is thought that including data derived from radiomics into the input flow of machine learning algorithms may improve the prediction of recurrence. Although some studies have shown glimmers of hope, more data is needed before offering practitioners tools to identify high-risk patients and enable extensive clinical application, especially regarding the matters of imaging normalization, radiomics process standardization and access to larger patient databases with external validation in order to allow results extrapolation. The aim of this review is to present a critical overview from this data.

A cytokine storm induced by SARS-Cov2 may produce pneumonitis which may be fatal for older patients with underlying lung disease. Hyper-elevation of Interleukin1 (IL-1), Tumor necrosis factor-1alfa (TNF-1 alfa), and Interleukin 6 (IL-6) produced by inflammatory macrophage M1 may damage the lung alveoli leading to severe pneumonitis, decreased oxygenation, and potential death despite artificial ventilation. Older patients may not be suitable candidates for pharmaceutical intervention targeting IL-1/6 blockade or artificial ventilation. Low dose total lung (LDTL) irradiation at a single dose of 50 cGy may stop this cytokine cascade, thus preventing, and/or reversing normal organs damage. This therapy has been proven in the past to be effective against pneumonitis of diverse etiology and could be used to prevent death of older infected patients. Thus, LDRT radiotherapy may be a cost-effective treatment for this frail patient population whom radiation -induced malignancy is not a concern because of their advanced age. This hypothesis should be tested in future prospective trials.

Background Esophageal cancer treatment requires large radiation fields due to the deep location of the esophagus in the mediastinum and the high incidence of radial spread. There is no optimal radiation technique to ensure appropriate target coverage and minimal dose to all normal structures. Methods Fifteen consecutive cases of locally advanced esophageal cancer treated with radical chemoradiation (CRT) were analyzed. The total prescribed dose was 50.4 Gy in 28 fractions. A total of 60 plans were generated for analysis, including four different methods for each case. Method 1 consisted of a four-field conformal technique; method 2 was a two-plan technique (antero-posterior (AP), postero-anterior (PA), two posterior oblique fields (RPO and LPO)); method 3 was a three-field conformal technique (AP, LPO, RPO); and method 4 was a volumetric modulated arc radiotherapy (VMAT) technique. Dose ratios were calculated using the minimum, maximum, mean, and median doses of methods 2-4 over the dose of method 1. Ratios for the planning target volume (PTV) and to surrounding organs were analyzed. Results The mean PTV dose ratio ranged from 0.994 to 1.048 (SD = 0.01) representing an adequate target coverage for all techniques based on an analysis of variance (ANOVA). For the lungs, method 2 had the lowest lung V20 with a ratio of 0.861 (SD = 0.12), whereas method 3 had the highest with 1.644 (SD = 0.14). For the heart, method 3 had the lowest heart V40 with a mean dose ratio of 0.807 (SD = 0.09), whereas method 2 had the highest with 1.160 (SD = 0.11). For the liver, method 2 had the lowest V30 with a mean ratio of 0.857 (SD = 0.1) whereas method 4 had the highest with 1.672 (SD = 0.48). For the spinal cord, method 3 had the lowest mean dose ratio of 0.559 (SD = 0.09) whereas method 2 had the highest with 1.094 (SD = 0.04). Conclusion The four radiation techniques for esophageal cancer treatment were appropriate for target coverage. Method 2 had the most organ-sparing effect for the lungs and liver, and method 3 for the heart and spinal cord. VMAT did not add any significant sparing. A case-by-case decision should be made based on the patient’s comorbidities.

Clinical complete response (cCR) in rectal cancer is being evaluated as a tool to identify patients who would not require surgery in the curative management of rectal cancer. Our study reviews mucosal changes after neoadjuvant therapy for rectal cancer in patients treated at our center. Pathology reports were retrieved for patients treated with neoadjuvant chemoradiation therapy (CRT) or high-dose rate brachytherapy (HDRBT). The macroscopic appearance of the specimen was compared with pathologic staging. This study included 282 patients: 88 patients underwent neoadjuvant CRT and 194 patients underwent HDRBT; all patients underwent total mesorectal excision (TME). There were 160 male and 122 female patients with a median age of 65 years (range 29–87). The median time between neoadjuvant therapy and surgery was 50 and 58 days. Sixty patients (21.2%) were staged as ypT0N0, 21.2% had a pathologic complete response (pCR), and only 3.2% had a cCR. Of the 67 patients with initial involvement of the circumferential radial margin (CRM), 44 converted to pathologic CRM−. Two hundred seventy-three patients (96.8%) had mucosal abnormalities. Of the 222 patients with residual tumor, 70 patients had no macroscopic tumor visualized but an ulcer in its place. Most patients undergoing neoadjuvant therapy for rectal cancer have residual mucosal abnormalities which preclude to a cCR as per published criteria from Brazil. Further studies are required to optimize clinical evaluation and MRI imaging in selected patients.

Aim High-dose-rate brachytherapy (HDRBT) appears to be associated with less treatment-related toxicity compared with external beam radiotherapy in patients with rectal cancer. The present study compared the effect of preoperative treatment strategies on overall survival, cancer-specific deaths, and local recurrences between a Dutch and Canadian expert center with different preoperative treatment strategies. Patients and methods We included 145 Dutch and 141 Canadian patients with cT3, non-metastasized rectal cancer. All patients from Canada were preoperatively treated with HDRBT. The preoperative treatment strategy for Dutch patients consisted of either no preoperative treatment, short-course radiotherapy, or chemoradiotherapy. Cox proportional hazards models were used to estimate hazard ratios (HR) with 95% confidence intervals (CIs) comparing overall survival. We adjusted for age, cN stage, (y)pT stage, comorbidity, and type of surgery. Primary endpoint was overall survival. Secondary endpoints were cancer-specific deaths and local recurrences. Results Five-year overall survival was 70.9% (95% CI 62.6%–77.7%) in Dutch patients compared with 86.9% (80.1%–91.6%) in Canadian patients, resulting in an adjusted HR of 0.70 (95% CI 0.39–1.26; p = 0.233). Of 145 Dutch patients, 6.9% (95% CI 2.8%–11.0%) had a local recurrence and 17.9% (95% CI 11.7%–24.2%) patients died of rectal cancer, compared with 4.3% (95% CI 0.9%–7.5%) local recurrences and 10.6% (95% CI 5.5%–15.7%) rectal cancer deaths out of 141 Canadian patients. Conclusion We did not detect statistically significant differences in overall survival between a Dutch and Canadian expert center with different treatment strategies. This finding needs to be further investigated in a randomized controlled trial.

High-dose-rate endorectal brachytherapy (HDREBT) is a novel treatment modality for patients with rectal cancer. It is based on modern tumor imaging, in particular magnetic resonance imaging (MRI), which is used to choose eligible patients and improve tumor visualization. Treatment planning is performed using 3D CT simulation and 3D treatment planning. Treatments are delivered on an outpatient basis and require minimal local anesthesia. Validation of this technique was carried out through a preoperative study. In this chapter, we describe the technical aspects of HDREBT and the ongoing studies exploring the clinical applications of this treatment modality for patients with rectal cancer: As neoadjuvant treatment for patients with operable rectal tumor As a dose escalation modality following external beam radiation for elderly and medically inoperable patients As a modality to promote to sphincter preservation surgery (SPS) for patients with low-lying rectal cancer As an option to improve local control in patients with newly diagnosed rectal cancer in the setting of previous pelvic radiation therapy

Purpose: We introduced the concept of Dynamic Modulated Brachytherapy (DMBT) for rectal cancer, last year. To continue our work, we studied different shield designs and investigated the system's tolerance against systematic setup errors. Methods: As previously presented, our system uses a cylindrical tungsten shield to create a directional radiation profile, which is modulated through translation and rotation using a specialized robotic arm. We used Monte Carlo simulations and an in‐house gradient projection optimization algorithm to look at key design parameters. First, we used ideal phantoms to study treatment quality from shield radii ranging 0.5–1.5 cm in 0.25 cm increments. Second, using 36 patient plans, the dependence on radial source position within the shield was studied. We also analyzed the tolerance of the system to systematic setup errors by simulating dose distributions from possible inaccuracies. These included translational and rotational errors as well as possible Ir‐192 source misplacements by the afterloading system. Results: Changes in shield radius followed steady patterns. Increasing the radius showed a consistent increase in dose conformality to the tumor volume and better sparing to surrounding tissues. However, there was also a linear increase in total dwell time. There was a trade off to changing the radial position of the source. As the source is brought away from the center, there is a decrease in conformality to the tumor volume, but sparing to healthy tissues was increased and there is a decrease in total dwell time. We found that any potential setup errors for our system, within anticipated margins, had negligible effects on the dose distributions (< 3% deviation). Conclusion: Various parameters for shield designs must be balanced for an effective DMBT application. It was found that the system is highly robust against systematic setup uncertainties.

Rectal cancers can be categorized into three clinical subgroups: early, intermediate, and those locally advanced. For the latter two cases, preoperative radiotherapy is recommended. An advanced type of cancer is diagnosed whenever a cT3 lesion threatens or invades mesorectal fascia or when a cT4 tumor overgrows into organs not readily resectable. For the intermediate-risk group, tumor shrinkage before surgery is not needed and preoperative radiotherapy is aimed at reducing the risk of local recurrence. There are two types of preoperative radiation treatment commonly accepted as standard for the intermediate risk group: (1) short-course (5 fractions of 5 Gy over 1 week) radiotherapy (RT) with surgery carried out within the next 5 days and (2) long-course chemoradiation (conventionally fractionated RT consisting of 25–28 fractions of 1.8 or 2 Gy over 5–5.5 weeks concomitantly used with 5-fluorouracil or capecitabine) with surgery carried out 6–8 weeks thereafter.

Intensity-modulated radiation therapy The introduction of computed tomography simulation and computer-based treatment planning in radiotherapy provided improved definition of target and normal structures, and lead to the era of 3D conformal therapy. However, it was the modern generation of linear accelerators, equipped with dynamic multileaf collimators, that truly revolutionized radiotherapy. Multileaf collimators consist of multiple, individually motorized leaves that are driven by sophisticated computerized algorithms, moving them in and out of the beam’s path, thereby modulating the beam’s intensity. These technological advancements precipitated the development of intensity-modulated radiotherapy (IMRT), enabling highly conformal radiation delivery with dose sculpting of target volumes and a rapid dose fall-off for the sparing of normal structures, or ‘organs at risk’ (OAR). Cumulative data on clinical tolerance and dose–effect correlations have allowed the definition of specific tolerance doses for OAR. Respecting these OAR dose limits while delivering the appropriate therapeutic dose to the clinical target volume (CTV) has been facilitated by the pairing of IMRT with image-guided radiotherapy, which allows for accurate tumor and OAR localization during radiotherapy planning and delivery. Ultimately, this has lead to an improvement in local tumor control in a variety of different tumor sites, while reducing the dose to OAR, thus diminishing radiation-related toxicity. IMRT has been particularly useful in the treatment of patients with head and neck cancer, whereby the sculpting of concave target doses permits dose restriction around the parotids. This has lead to parotid function preservation while achieving identical local disease control. Thus, patient quality of life has been improved by the decrease in xerostomia observed in conventional r adiation treatment [1]. Subsequently, IMRT was studied for pelvic tumors, starting with gynecologic malignancies. Dosimetric studies analyzing dose–volume histograms showed significant dose sparing for OAR, especially for the small bowel, bladder, rectum and bone marrow [2,3]. Subsequent clinical studies substantiated these predicted benefits, with lower reported gastrointestinal (GI) toxicity [4,5], pelvic girdle toxicity [6]

Pain and anxiety have been reported as primary concerns for patients with head-and-neck, gynecologic, and prostate cancers undergoing high dose rate (hdr) brachytherapy. However, almost no research has been published on the degree to which these symptoms are experienced by rectal cancer patients undergoing hdr brachytherapy. We conducted a pilot study examining the experiences of rectal cancer patients during hdr brachytherapy, specifically the intensity and trajectory of their anxiety and pain. Rectal cancer patients (n = 25) who received hdr brachytherapy treatment at a hospital in Montreal, Quebec, completed verbal analog scales for pain and anxiety at 4 time points over 4 treatment days. On all 4 days, a subset of patients reported moderate-to-severe anxiety before applicator insertion. Pain increased significantly from the time patients were lying on the table to immediately after insertion of the applicator (p < 0.001). Insertion of the applicator appears to be the most painful part of the procedure, and although anxiety declined to below baseline after applicator removal, pain remained somewhat elevated. Some patients required conscious sedation, however, reports of moderate-to-severe pain were more frequent from patients who received pain medications than from patients who did not receive such medication (p < 0.05). Most patients with rectal cancer tolerated hdr rectal brachytherapy well, although the procedure is stressful and painful for some. Insertion of the applicator was found to be the point of maximal pain, and medication was not always completely successful at alleviating the pain, suggesting that additional psychosocial interventions might be needed, with particular emphasis on the time of applicator insertion.

The management of older cancer patients remains difficult because of data paucity. Radiation oncologists need to identify potential issues which could affect treatment of those patients. A workshop was organized in Barcelona among international radiation oncologists with special interest in the management of older cancer patients on April 22, 2018. The following consensus was reached: 1. Older cancer patients often faced unconscious discriminating bias from cancer specialists and institutions because of their chronological age. 2. Advances in radiotherapy techniques have allowed patients with multiple co-morbidities precluding surgery or systemic therapy to achieve potential cure in early disease stages. 3. The lack of biomarkers for frailty remains an impediment to future research. 4. Access to healthcare insurance and daily transportation remains an issue in many countries; 5. Hypofractionation, brachytherapy, or stereotactic techniques may be ideally suited for older cancer patients to minimize transportation issues and to improve tolerance to radiotherapy. 6. Patients with locally advanced disease who are mentally and physically fit should receive combined therapy for potential cure. 7. The role of systemic therapy alone or combined with radiotherapy for frail patients needs to be defined in future clinical trials because of targeted agents or immunotherapy may be less toxic compared to conventional chemotherapy.

Purpose During the last decade due to the availability of a CT scan in the brachytherapy suite, high-dose-rate endorectal brachytherapy (HDREBT) has evolved as a CT-based daily adaptive treatment. An update of the technical and practical aspects of HDREBT is provided. Methods and Materials Description of technical and practical aspects of HDREBT focused on the preoperative treatment of locally advanced rectal cancer. During preoperative HDREBT, 26 Gy is delivered in four daily applications of 6.5 Gy prescribed to the 100% isodose, covering the clinical target volume. Daily CT scans are obtained and used for plan optimization, leaving patient positioning unchanged between CT scan and treatment delivery. Results All steps of HDREBT treatment procedure are discussed in detail: flexible proctosigmoidoscopy and clipping; patient setup; applicator placement; target delineation; treatment planning and delivery; and patient care. Afterward, treatment results are reviewed. Conclusions CT-based adaptive preoperative HDREBT is a practical and feasible therapy for locally advanced rectal cancer, offering excellent local control with a favorable toxicity profile.

Radiotherapy has been driven by constant technological advances since the discovery of X-rays in 1895. Radiotherapy aims to sculpt the optimal isodose on the tumour volume while sparing normal tissues. The benefits are threefold: patient cure, organ preservation and cost-efficiency. The efficacy and tolerance of radiotherapy were demonstrated by randomized trials in many different types of cancer (including breast, prostate and rectum) with a high level of scientific evidence. Such achievements, of major importance for the quality of life of patients, have been fostered during the past decade by linear accelerators with computer-assisted technology. More recently, these developments were augmented by proton and particle beam radiotherapy, usually combined with surgery and medical treatment in a multidisciplinary and personalized strategy against cancer. This article reviews the timeline of 100 years of radiotherapy with a focus on breakthroughs in the physics of radiotherapy and technology during the past two decades, and the associated clinical benefits.

Magnetic resonance imaging (MRI) is highly accurate in local staging of rectal cancer. It can identify features known to be associated with increased risk of metastatic disease. We evaluated the incidence of synchronous metastatic disease on fludeoxyglucose–positron emission tomography/computed tomography (FDG-PET/CT) and contrast-enhanced multiple-row detector computed tomography (ceMDCT) in MRI-stratified high- and low-risk rectal cancers. The aim was to determine the incidence of synchronous metastatic disease according to MRI risk features. A total of 236 patients with rectal cancer were recruited to a study evaluating FDG-PET/CT. All patients underwent MRI staging and were stratified into high and low risk (high risk: extramural venous invasion, extramural spread of >5 mm or T4, involved circumferential resection margin or intersphincteric plane involved for low rectal tumors). Confirmed metastases were those identified on FDG-PET/CT and ceMDCT. Imaging data were available for 230 (97.5%) of 236 patients. Incidence of confirmed distant metastases was significantly greater in the MRI high-risk group, with 28 (20.7%) of 135 (95% confidence interval [CI] 14.8–28.3), versus the low-risk group, with 4 (4.2%) of 95 (95% CI 1.7–10.3) (odds ratio 6.0, 95% CI 2.0–17.6, P

Radiation-induced dermatitis is a common side effect of breast irradiation, with hypofractionation being a well-known risk factor. In the context of the widespread adoption of hypofractionated breast radiotherapy, we evaluated the effect of hypofractionated radiotherapy on the incidence of skin toxicity in patients receiving adjuvant chemotherapy. We retrospectively reviewed the records of patients with breast cancer treated from 2004 to 2006 at a single institution. Patients undergoing lumpectomy with or without adjuvant chemotherapy followed by hypofractionated radiotherapy consisting of 42.4 Gy in 16 fractions were included in the study. Using cosmetic and skin toxicity scales, all patients were evaluated weekly during treatment and at scheduled follow-up visits with the radiation oncologist. During the study period, 162 patients underwent radiotherapy, and 30% of those (n = 48) received chemotherapy. Radiotherapy boost to the tumour bed was more common in the chemotherapy group [n = 20 (42%)] than in the radiotherapy-alone group [n = 30 (26%)]. We observed no statistically significant difference between the groups with regard to acute skin toxicity of grade 3 or higher (2.1% in the chemotherapy group vs. 4.4% in the radiation-alone group, p = 0.67) or of grades 1&ndash, 2 toxicity (62.5% vs. 51.7% respectively, p = 0.23). There was also no significant difference in late grade 3 or higher skin toxicity between the groups (2.1% vs. 0% respectively, p = 0.30) or in grades 1&ndash, 2 toxicity (20.8% vs. 25.5% respectively, p = 0.69). Similarly, excellent or good cosmetic result scores were similar in both groups (p = 0.80) In our single-institution review, we observed no adverse effects of chemotherapy in combination with hypofractionated whole-breast irradiation. Further investigations are necessary to better elucidate the effects of chemotherapy on skin toxicity in the context of hypofractionated irradiation.

Over the past three decades, local-regional tumor control in rectal surgery has dramatically changed with the recognition of the importance of achieving tumor-free circumferential resection margins. This has led to the use of standardized total mesorectal excision (TME), with significant improvement in local control. Preoperative external beam radiation therapy (EBRT) has further increased the success of TME by reducing the rate of local relapse by half. However, the significant long term complication associated with EBRT is the price attached to this additional benefit. High Dose Rate Endocavitary Brachytherapy (HDREBT) appears to carries similar local control benefit but with minimal acute and long term complication rates. HDREBT technology was originally developed at McGill University. It uses the advantages of the modern imaging techniques to better visualize and target the local disease. From 1998 to 2008, 285 rectal cancer patients have been treated with preoperative HDREBT. All patients had endorectal ultrasound and pelvic Magnetic Resonance Imaging (MRI) for pretreatment tumour staging. At a median follow-up of 55 months, the 5 years actuarial local relapse rate was 5% with a disease free survival rate (DFS) of 65% and overall survival rate (OS) of 68%. At the time of surgery 27% had complete pathological response (PCR) and 37% had only microscopic residual disease. Grade III acute proctitis occurred in only 1% of the patients and there were no long term pelvic fracture. The present data suggests that HDREBT is an effective approach for rectal cancer patients requiring preoperative radiation therapy, with favorable acute and delayed toxicity profile. However, firm conclusions can only be drawn from a phase III multi-institutional study.

Objective: To compare the independent prognostic effect of a panel of immunohistochemical protein markers in colorectal cancer (CRC) and determine their ranking among the established prognostic factors T stage, N stage, vascular invasion, tumour budding and tumour grade. Design: A tissue microarray of 1420 CRCs was immunostained for 23 markers and mismatch repair (MMR) proteins. Immunoreactivity was assessed semi-quantitatively. Receiver operating characteristic (ROC) curves were used to determine cut-off scores for tumour marker positivity. Survival time was investigated for each marker in multivariable analysis with T stage, N stage, vascular invasion, tumour budding and tumour grade. The hazard ratio (HR) was used to compare the prognostic effect of each marker on 5 year survival. Results: To the standard prognostic features, only six markers added independent prognostic information including receptor for hyaluronic acid mediated motility (RHAMM) (HR = 2.39 (1.88 to 3.05)), epidermal growth factor receptor (HR = 1.65 (1.31 to 2.09)), tumour infiltrating lymphocytes (HR = 0.7 (0.54 to 0.92)), urokinase plasminogen activator (HR = 1.38 (1.09 to 1.75)), Raf-1 kinase inhibitor protein (HR = 0.75 (0.58 to 0.96)) and mammalian sterile 20-like kinase 1 (MST1) (HR = 0.75 (0.58 to 0.95). Diffuse (>90% staining) expression of RHAMM ranked above T stage, vascular invasion, tumour budding and tumour grade in terms of adverse prognostic significance and was associated with distant metastasis (p = 0.012) and with worse outcome in patients with metastatic disease (p = 0.031). Conclusions: The strong adverse effect of RHAMM on outcome in addition to its position within the hierarchy of well-established prognostic factors suggest that RHAMM should be considered a more important prognosticator than tumour grade, tumour budding and vascular invasion in patients with CRC.

Purpose In the past, film dosimetry was developed into a powerful tool for external beam radiotherapy treatment verification and quality assurance. The objective of this work was the development and clinical testing of the EBT3 model GafChromic film based brachytherapy quality assurance (QA) system. Methods and Materials Retrospective dosimetry study was performed to test a patient-specific QA system for preoperative endorectal brachytherapy that uses a radiochromic film dosimetry system. A dedicated phantom for brachytherapy applicator used for rectal cancer treatment was fabricated enabling us to compare calculated-to-measured dose distributions. Starting from the same criteria used for external beam intensity-modulated radiation therapy QA (3%, 3 mm), passing criteria for high- and low-dose gradient regions were subsequently determined. Finally, we investigated the QA system's sensitivity to controlled source positional errors on selected patient plans. Results In low-dose gradient regions, measured dose distributions with criteria of 3%, 3 mm barely passed the test, as they showed 95% passing pixels. However, in the high-dose gradient region, a more stringent condition could be established. Both criteria of 2%, 3 mm and 3%, 2 mm with gamma function calculated using normalization to the same absolute dose value in both measured and calculated dose distributions, and matrix sizes rescaled to match each other showed more than 95% of pixels passing, on average, for 15 patient plans analyzed. Conclusions Although the necessity of the patient-specific brachytherapy QA needs yet to be justified, we described a radiochromic film dosimetry–based QA system that can be a part of the brachytherapy commissioning process, as well as yearly QA program.

Background Infection with high risk human papillomavirus (HPV) is strongly associated with anal cancer. However, detailed studies on HPV type distribution by gender and age are limited. Methods Retrospective study of 606 invasive anal cancers diagnosed between 1990 and 2005 in two large urban areas of the province of Quebec, Canada. Cases were identified from hospitalization registry. Patient characteristics were collected from medical files. Archived anal squamous cancer specimens were available from 96 patients and were tested for HPV DNA and typing. Variant analysis was performed on 16 consecutive and 24 non-consecutive HPV16-positive samples to assess potential contamination during amplification. Results Among the 606 patients with anal cancers, 366 (60%) were women. Median age at diagnosis was 63 years. HPV was detected in 88/96 (92%) of cases. HPV16 was the most frequent type detected in 90% of HPV-positive specimens. Other types including 6, 11, 18, 33, 52, 53, 56, 58, 62 and 82 were also found. HPV 97 was not detected. HPV prevalence was associated with female gender and younger age. No contamination occurred during amplification as shown by the subset of 41 HPV16-positive samples, as 37, 2 and 1 isolates were from the European, African and Asian lineages, respectively. The most frequent variants were G1 ( n =22) and the prototype ( n =12). Conclusions Women with anal cancer are at higher risk for anal HPV infection, and HPV infection, especially HPV16, is strongly associated with squamous anal cancer. Therefore, HPV vaccine could potentially prevent the occurrence of anal cancer in both men and women.

Purpose: The goal of this study is to test the possible use of the analytical decomposition of differential uptake volume histograms (dUVHs) obtained from FDG-PET/CT data to isolate sub-volumes within a tumor known as biological target volumes (BTVs). Methods: : A retrospective study was conducted on a cohort of 20 histo-pathologically confirmed rectal adenocarcinoma patients having PET/CT scans for staging. All patients (T3N0) underwent pre-operative endorectal brachytherapy. After surgery, patients were restaged: 10 patients were T0N0 and 10 were restaged as remaining T3N0. The extent of the disease was sampled in order to create dUVHs; subsequently decomposed into the fewest number of analytical Gaussian functions. Results: With the assumption that each function fit corresponded to a single sub-volume within the tumor, six sub-volumes were found to consistently emerge. The first two sub-volumes were influenced by contouring and were not considered in the analysis. For the T3N0 population, abundances for volumes V3-V6 were 63.6%±11.3%, 25.7%±8.4%, 6.1%±4.9%, and 4.7%±2.6%. For the T0N0 population, they were 50.2%±6.8%, 33.4%±4.3%, 11.8%±7.6%, and 4.7%±2.4%. The two populations were compared using two tailed T-tests: volumes 3 and 4 were statistically different with p values of 0.021 and 0.056 respectively. V6 was located at 8.63 ± 2.2 for T0N0 and 6.14 ± 0.78 for T3N0 group (p=0.016). Conclusion: We described a method for dUVH decomposition using FDG-PET images of rectal adenocarcinoma patients that subsequently went for pre-operative brachytherapy. In addition to extracting different sub-volumes corresponding to different FDG uptake levels, we observed different abundances of two sub-volumes as well as positions of the maximum uptake between the two patient groups. In addition to opening the door to further investigation into underlying physiological phenotypes of segmented subvolumes and their use for biological radiotherapy treatment planning, this method may also provide parameters that could correlate to clinical outcomes in radiotherapy patients.

Aim Total mesorectal excision with preoperative radiotherapy reduces local recurrence in rectal cancer, but radiotherapy increases the risk of complications. This study compared the immediate postoperative outcome after external beam radiotherapy with outome after high-dose-rate endorectal brachytherapy (HDREBT). Method Patients (n = 318) treated with preoperative HDREBT (6.5 Gy, daily, over 4 days) followed by surgery 4–8 weeks later were matched with 318 patients from the Swedish Rectal Cancer Register treated with short-course radiotherapy (SCRT; 5 Gy, daily, over 5 days) and surgery in the subsequent week and with 318 patients who had surgery only (i.e. no preoperative radiotherapy; RT-) All 954 patients were followed for 30 days after surgery. Complications were divided into surgical, cardiovascular and infectious. Results The SCRT group had fewer cardiovascular complications (3.1%) than did HDREBT (9.4%, P = 0.002) and RT- (7.2%, P = 0.03) groups. There was less perioperative bleeding in HDREBT patients (379.3 ml) than in SCRT (947.2 ml; P