Overall Treatment Time Research Articles

Six fractions weekly as accelerated fraction radiotherapy: Is it applicable for nasopharyngeal cancer? A review

Standard therapy for nasopharyngeal cancer (NPC) is concurrent chemoradiation. Nevertheless, therapeutic outcomes are often unsatisfactory particularly for locally advanced stage. To enhance the therapeutic outcome, we may consider using altered fraction radiotherapy. Altered fraction radiotherapy is divided into two large groups for the therapy of NPC: hyperfraction radiotherapy and accelerated fraction radiotherapy. One of the accelerated fraction regimens suitable for NPC therapy is an accelerated regimen of six radiotherapy fractions weekly. This regimen is considered safe whether using conventional 2D planning technique or advance technique. Response to radiotherapy is better owing to the decrease in overall treatment time (OTT). Furthermore, acute or late side effects for this therapy are not very different to those of standard therapy. The conclusion is that we recommend the use of an accelerated regimen of six radiotherapy fractions weekly for locally advanced stage NPC with contraindication to concurrent chemoradiation, due to the high degree of clinical outcome as well as better tolerated side effect for NPC patients, particularly for those with locally advanced stage NPC.

Patterns of cervical cancer brachytherapy in India: results of an online survey supported by the Indian Brachytherapy Society.

PurposeCervical cancer is the most common gynecological cancer in India. Uniform protocol-based treatment is important for achieving optimal outcomes. We undertook a survey to investigate patterns of care with special regard to patterns of care in cervical cancer brachytherapy in India.Material and methodsA 17-question online survey was sent to radiation oncologists across India. Respondents were required to have a minimum of 1-year experience. One response per center was accepted and deemed as representative.ResultsOut of 116 centers, 59 responses were generated. Two-thirds (66.1%) were from academic centers and the majority (96.6%) used high-dose-rate (HDR) brachytherapy. The centers treated an average of 255 patients per year (median 161 patients, IQR 76-355). The majority were locally advanced cancers (FIGO 2009 stage II-IV 87.5%). External beam radiotherapy (EBRT) schedules were fairly consistent, administering doses of 45-50 Gy over 5 weeks. Brachytherapy was performed towards EBRT completion by 37/59 (62%) and 43/59 (74.3%) centers used a schedule of 7 Gy × 4 fractions (HDR). Brachytherapy was commonly performed under anesthesia (spinal/general: 44% each) with ultrasound (USG) guidance (29%). Computed tomography (CT) imaging (65%) and orthogonal X-rays (35%) represented the most common imaging for planning, while point A prescription (66%) or GEC-ESTRO based parameters (35%) with manual/geometric methods represented the most common methodology for dose volume prescription and optimization. Overall treatment time (OTT) reported was within 49-56 days in 50%. Complex implants (IC + IS) were performed for more than 30% of cases by 3 centers.ConclusionsOur survey suggested a fairly uniform treatment paradigm for cervical cancer brachytherapy, with a progressive shift from 2D to 3D image-based parameters for planning, with persistence of point A based prescription. Further efforts are needed to augment and ease this transition.

299. Prostate cancer dose-fraction sensitivity deduced from radiotherapy outcome of 17949 patients

Purpose Aim of the work is to model biochemical free survival at five year (5 y BCFS), based on literature clinical outcome data available until now and to evaluate parameters describing dose-fractionation radiosensitivity and repopulation. Methods Twenty-six data sets published in literature reporting the 5 y BCFS, dose scheduling, androgen deprivation therapy (ADT) and clinical variables, have been considered for a total of 17949 prostate cancer patients treated with external beam radiation therapy (EBRT), with and without ADT with dose per fraction from 1.80 Gy/fr to 7.25 Gy/fr and overall treatment time (OTT) from 1 week to 10 weeks. Fifteen patients groups have been built considering the risk class and the use of ADT. At first, for each group, D50 and g50 parameters were calculated. Then, dprolif, Tprolif and α / β parameters have been evaluated considering three hypothesis: dependence and not on OTT and dependence only on OTTs difference. Results The median values of D50 and g50 were 57 Gy and 1.7 for low risk patients, 61 Gy and 1.8 for intermediate risk patients and 68 Gy and 1.9 for high risk patients. For intermediate and high risk patients, a reduction of 4 Gy for D50 and 0.5 for g50 for ADT respect to no ADT treated patients was found. Not considering OTT dependence, the median α / β value parameter was in the range 0.8 Gy–2.6 Gy for the groups analysed. Median value of the dprolif was in the range 0.0 Gy/d–0.3 Gy/d while a median value of Tprolif parameter greater than 20 days was obtained. Conclusions Low α / β values have been confirmed for each risk class and the use of ADT seems to reduce median α / β values for intermediate and high risk patients. α / β values lower than values for late normal tissue morbidity increase and support the interest of hypofractionated radiotherapy schedules for all risk groups.

32. Linac based VMAT radiosurgery for multiple brain lesions: comparison between a conventional multi-isocenter approach and a new dedicated mono-isocenter 4π technique (HyperArc™)

Purpose Linac based VMAT radiosurgery (SRS) of multiple brain lesions (MBL) is typically performed by a multiple-isocenter approach, i.e.one isocenter per lesion.Here we present the worldwide first experience with a new mono-isocenter technique with multiple non-coplanar arcs (HyperArc, Varian Inc.)in terms of a plan comparison with a multiple-isocenter approach. Methods From August to October 2017, 20 patients with MBL (mean 5, range 2–10) have been treated by HyperArc: prescribed doses ( D p ) were 18–25 Gy in single-fraction, and 21–27 Gy in three-fractions.Total PTV, defined by a 2 mm isotropic margin from each lesion, had mean size of 9.6 cm3 (range 0.5–27.9 cm3).HyperArc VMAT plans (HA), with 5 non-coplanar 180°-arcs (couch at 0°, ±45°, ±90°), and multiple-isocenter VMAT plans (RA), with 2 coplanar 360°-arcs per isocenter, were generated.100% D p at 98%PTV was prescribed, and D 2 % (PTV) D p was accepted.Constraints for 1(3) -fraction to the brainstem, D 0.5cc D 0.5cc V 12 and mean dose to the brain-minus-PTV, MU and overall treatment time (OTT) per fraction.OTT was measured for HA treatments, whereas estimated (3 min.for patient setup plus 5 min.for each CBCT per isocenter) for RA plans. Results As detailed in Table 1 , HA plans resulted in significantly improved CI ( p V 12 to the brain-minus-PTV (p = .023), MU (p D p isodose shells around the targets for the HA plans is depicted for an example patient.By contrast, no significant difference in terms of mean doses to the brain-minus-PTV resulted (p = .31). Conclusions For linac based VMAT-SRS of MBL, HyperArc plans assured a higher CI and a lower GI, a lower V 12 to the brain-minus-PTV, and a lower OTT than standard multiple-isocenter VMAT plans. Finally, all HyperArc treatments were completed within a typical 20 min. time slot.

Local Control Analyses of Pulmonary Oligometastases Treated By Stereotactic Body Radiation Therapy (SBRT) from a Multi-institutional Survey in Japan

This study aimed to investigate local control (LC) rate and to identify affecting factors for LC of pulmonary oligometastases treated by SBRT using large data sets from a multi-institutional nationwide survey in Japan. A total of 1374 patients with 1545 targets from 68 institutions were collected. Eligibility was as follows: SBRT for pulmonary oligometastases was performed between 2004 January and 2015 June, biological effective dose (BED10) was 75 Gy or more. Local recurrence of thoracic primary tumor was excluded and all extrathoracic lesions were controlled at the time of SBRT. Cumulative LC rate was calculated using Kaplan-Meier method and the 95% confidence interval (95% CI) was calculated using Greenwood's formula. Cox proportional hazards model was applied for LC analyses and variables with a p-value of < 0.20 in univariate analyses were put in multivariate analysis (MVA). The median targeted tumor diameter was 1.5 cm (range, 0.3-6.5), and the median overall treatment time (OTT) of SBRT was 7 days (range, 3-81). Dose calculation algorithm was divided into type B (51.7%) which was equivalent of Analytical Anisotropic Algorithm, type C (9.3%) which was equivalent of Monte Carlo Algorithm and type A (34.8%) which was older generation algorithm than both. The median heterogeneity correction considered BED10 around isocenter was 126.9 Gy (range, 76.8-352.7). Primary sites were separated into lung (29.1%), colorectum (25.3%), genitourinary (13.5%), head and neck (8.6%), esophagus (8.5%) and others. Median follow-up period was 24.2 months (range, 0.1-143.7). Local recurrence occurred in 222 tumors and median time to local recurrence was 12.4 months (range, 2.9-98.7). Estimated 1-year, 3-year and 5-year LC were 92.0% (95% CI, 90.4-93.4%), 81.3% (95% CI, 76.7-83.6%) and 78.5% (95% CI, 75.6-81.2%), respectively. The result of MVA (n=785) showed that maximum diameter of targeted tumor (per 1 cm increase; Hazard ratio [HR], 1.320; p=0.023), dose calculation algorithm (type B vs. type A; HR, 0.541; p=0.012), OTT (per 10 days prolonged; HR, 0.564; p=0.022) and primary site of metastases were significantly associated with LC. In regard to primary sites, colorectum showed significantly lower LC rate compared to lung (HR, 2.837; p<0.001), genitourinary (HR, 6.473; p<0.001), head and neck (HR, 4.879; p<0.001) and others (HR, 2.478; p=0.005), genitourinary showed significantly better LC compared to colorectum (HR, 0.154; p<0.001) and esophagus (HR, 0.291; p=0.020) but the others showed no significant association. BED10 showed the tendency (per 10 Gy increase; HR, 0.924; p=0.102). To procure excellent LC rate, the use of type A algorithm should be avoided, the strategy of tumor diameter and primary sites should be considered and higher BED with longer OTT might help.

Initial Response Lag time in Flat versus Non-Flat Beam Frameless Image Guided Trigeminal Radiosurgery

Radiosurgery is an established option in trigeminal neuralgia. Irrespective of devices used, the pain relief with radiosurgery occurs after a lag time of about 6-8wks. Recent introduction of FFF beams with dose rates around 2000mu/mt results in abbreviated beam-on time (BOT) - 12mts & overall treatment time (OTT) - 22-28 mts. Purpose of this study is to analyse the pain response lag time in trigeminal radiosurgery using unflat beams (@dose rate 2000) and flat beams (@dose rate 600). Twenty consecutive patients aged between 33-88 yrs with Trigeminal neuralgia (Typical -17, Atypical-3) underwent double reinforced mask immobilisation, CT (0.725mm post contrast axial) and MR simulation (0.75mm 3D space, 3-D TOF sequences). Following rigid fusion, a single isocenter was positioned at either RGZ or the DREZ along the symptomatic trigeminal nerve to deliver doses of 75-80 gy prescribed to 90% isodose line. All patients underwent treatment on a C-arm linac with 5mm stereotactic cones, 9 arcs with 3D-CBCT image guidance for positional accuracy. Sub-mm and sub-degree precision all through treatment was achieved using 6-DOF robotics & intra-fraction imaging after every 4000 mu delivery. 10 consecutive pts who underwent treatment with Unflat beams were compared with retrospective cohort of 10 patients who underwent treatment with flat beams. The pain outcome of patient, Lag time for response, pain recurrence, and treatment-related complications were evaluated. Cox regression analyses was used to evaluate the time to response and the duration of pain relief in relation to the type of beams used. Using the Barrow Neurological Index (BNI) pain score, 9 cases (90%) and 8 cases (80%) of unflat and flat beams Radiosurgery achieved treatment success (BNI pain score I–IIIb) within first 2months. However the Median time to initial response after the Radiosurgery was significantly shorter in the unflat beam cohort (mean 2.5 weeks) than in the Flat beam cohort (mean 6.4 weeks) (p=0.044). There were 5 pts in BNI 1 & 2 within first 1 month post radiosurgery for unflat beams. Frequency of facial numbness was lower in the Unflat beams compared to the Flat beams (0%, 10%). Faster treatments are associated with less patient mobility and increased delivery accuracy. Prolonged duration of radiosurgery amplifies the impact of Increased submm mobility of the nerve in the prepontine cistern, factor never considered, & which might negatively affect the amount of clinically relevant fibers receiving the minimal radiation dose necessary to block excessive sensory information. To the best of our knowledge, this is the first study reported in literature which looked into the impact of the abbreviated treatment times on pain outcomes using unflat beams for trigeminal radiosurgery. Larger study is initiated to study the effects of dose rates on pain outcomes.

Evaluating the potential benefit of reduced planning target volume margins for low and intermediate risk patients with prostate cancer using real-time electromagnetic tracking

PurposeThe aim of this study is to quantify and describe the feasibility, clinical outcomes, and patient-reported outcomes of reduced planning target volume (PTV) margins for prostate cancer treatment using real-time, continuous, intrafraction monitoring with implanted radiation frequency transponder beacons. Methods and materialsFor this prospective, nonrandomized trial, the Calypso localization system was used for intrafraction target localization in 31 patients with a PTV margin reduced to 2 mm in all directions. A total of 1333 fractions were analyzed with respect to movement of the prostate, pauses and interruptions, and dosimetric data. Pre- and posttreatment quality-of-life scores were tracked at baseline, during treatment, and up to 24 months after treatment. ResultsThe mean time of daily treatment was 10 minutes, with 96.1% of all treatments falling within a 20-minute treatment window standard. On average, beacon motion exceeded 3 mm during active treatment only 1.76% of the time. The average length of treatment interruption was 34.2 seconds, with an average of 1 interruption every 3.39 fractions. The displacement or excursion of the prostate was the greatest in the superior or inferior dimension (0.11 mm and 0.09 mm, respectively) and anterior or posterior dimension (0.07 mm and 0.13 mm, respectively), followed by the left or right dimension (0.05 mm and 0.06 mm, respectively). At 6 months, patients demonstrated a smaller change in Expanded Prostate Cancer Index Composite scores than the ProtecT comparator group (decreased short-term morbidity). However, in the Bowel and Urinary domains at 12 and 24 months, there was no significant difference. ConclusionsOur data confirm and support that the use of Calypso tracking with intensity modulated radiation therapy reliably provides minimal disruption to daily treatments and overall time of treatment, with the PTV only moving outside of a 3-mm margin < 2% of the time. The use of a 3-mm PTV margin provides adequate dosimetric coverage while minimizing genitourinary and gastrointestinal toxicity.

Stereotactic ablative body radiotherapy in patients with prostate cancer.

Prostate is the most common non-cutaneous cancer diagnosed among men in North America. Fortunately most prostate cancers are screen detected and non-metastatic on diagnosis. Treatment options for men with localized prostate cancer include surgery ± postoperative radiation or radiation ± androgen deprivation therapy (ADT). Brachytherapy ± external beam radiation treatment (EBRT) appears to have superior long-term disease control over EBRT alone likely because of higher biologic effective dose delivered. Stereotactic ablative body radiation (SABR) is a novel, non-invasive, high-precision EBRT technique that allows safe delivery of biologic doses similar to brachytherapy with similar or lower side effects [measured using toxicity or quality of life (QOL) scales]. Efficacy for SABR appears to be similar to brachytherapy including positive biopsy rates 2–3 years post treatment, biochemical failure (BF) rates out to 10-year and incidence of metastases. SABR dose escalation reduces biopsy positivity and prostate-specific antigen (PSA) nadirs but increases genitourinary (GU) and gastrointestinal (GI) toxicity—no effect on BF has been realized yet. The overall treatment time (OTT) varies in many protocols. Phase 2 randomized data shows that QOL is better in the acute setting with a weekly course of treatment compared to an every other day treatment regimen with no difference in late setting. Follow-up data are immature and likely underpowered to determine efficacy differences. SABR is cheaper and uses less resource than any other radiation technique. Given the healthcare resource challenges (including financial resources), SABR would be a welcomed addition if studies show non-inferiority to other radiation techniques. For patients with de novo or metastatic disease on relapse, there is much enthusiasm regarding the use of SABR in the setting of oligometastatic prostate cancer. SABR appears to be feasible to deliver, well tolerated and may delay the next line of therapy. However, until adequately powered randomized studies confirm a benefit, such an approach cannot be considered standard of care treatment at this time. Enrollment of eligible prostate cancer patients onto SABR clinical trials should be encouraged.

Impact of Time Factors on Outcome in Patients with Head and Neck Cancer Treated with Definitive Radio(Chemo)Therapy.

To evaluate treatment-related factors such as overall treatment time (OTT) and radiation treatment time (RTT) in head-and-neck cancer. A total of 216 patients with locoregionally advanced inoperable head and neck cancer were treated with definitive radio(chemo)therapy. Mean follow-up was 37 months. Median time from diagnosis to start of radiotherapy (total waiting time) was 34 days, and comprised of referral waiting time and time for preparatory work. Median RTT was 40 days, and median OTT was 91 days. At 6, 12 and 24 months local recurrence-free survival (LRFS) was 75%, 65% and 60%; metastasis-free survival (MFS) was 84%, 77% and 70%; overall survival (OS) was 72%, 58% and 40%. Tumor stage, boost and chemotherapy were significant for OS, waiting time for preparatory work and RTT were significant for MFS, and referral waiting time and total radiotherapy dose for LRFS. RTT ≤40 days was a prognostic factor for better MFS. Prolonged waiting time had a converse effect for radiotherapy with better outcome on MFS and LRFS.

Impact of change in serum albumin level during and after chemoradiotherapy in patients with locally advanced esophageal cancer.

In patients with locally advanced esophageal cancer treated by concurrent chemoradiotherapy (CCRT), baseline malnutrition and its progression have been shown to be associated with a poor outcome. We conducted this study to determine the variation in four blood test parameters including serum albumin level (ALB), creatinine (Cre), hemoglobin (Hb) and platelet (Plt) during CCRT for stage III esophageal cancer patients and its effect on patients' outcome. One hundred eighty-three patients diagnosed with stage III esophageal cancer were retrospectively investigated. In addition to known prognostic factors, baseline level of the four blood test parameters and their variation at day 105 (ΔALB, ΔCre, ΔHb and ΔPlt, respectively) were analyzed. The median observation period for patients who survived was 57.2months, and the 5-year overall survival rate was 35.6% (95% CI 34.2-36.9%). In multivariate analyses, baseline ALB (≥ 3.6g/dL), higher ΔALB (≥ + 0.3g/dL) were independent predictors for overall survival (p = 0.001 and < 0.001, respectively), in addition to other clinical factors including T stage and overall treatment time (OTT). For disease-free survival, ΔALB was only a predictor in hematological parameters (p = 0.001) in addition to T stage and OTT. No hematological and clinical parameters had significant correlation with local control in multivariate analysis. Furthermore, ΔALB showed significant correlation with OS and DFS in log-rank test (p = 0.002 and 0.002, respectively). Our results suggest improvement in ALB after treatment might be a favorable prognostic factor in esophageal cancer patients treated by CCRT.

Linac-based VMAT radiosurgery for multiple brain lesions: comparison between a conventional multi-isocenter approach and a new dedicated mono-isocenter technique

BackgroundLinac-based stereotactic radiosurgery or fractionated stereotactic radiotherapy (SRS/FSRT) of multiple brain lesions using volumetric modulated arc therapy (VMAT) is typically performed by a multiple-isocenter approach, i.e. one isocenter per lesion, which is time-demanding for the need of independent setup verifications of each isocenter. Here, we present our initial experience with a new dedicated mono-isocenter technique with multiple non-coplanar arcs (HyperArc™, Varian Inc.) in terms of a plan comparison with a multiple-isocenter VMAT approach.MethodsFrom August 2017 to October 2017, 20 patients with multiple brain metastases (mean 5, range 2–10) have been treated by HyperArc in 1–3 fractions. The prescribed doses (Dp) were 18–25 Gy in single-fraction, and 21–27 Gy in three-fractions. Planning Target Volume (PTV), defined by a 2 mm isotropic margin from each lesion, had mean dimension of 9.6 cm3 (range 0.5–27.9 cm3). Mono-isocenter HyperArc VMAT plans (HA) with 5 non-coplanar 180°-arcs (couch at 0°, ±45°, ±90°) were generated and compared to multiple-isocenter VMAT plans (RA) with 2 coplanar 360°-arcs per isocenter. A dose normalization of 100%Dp at 98%PTV was adopted, while D2%(PTV) < 150%Dp was accepted. All plans had to respect the constraints on maximum dose to the brainstem (D0.5cm3 < 18 Gy) as well as to the optical nerves/chiasm, eyes and lenses (D0.5cm3 < 15 Gy). HA and RA plans were compared in terms of dose-volume metrics, by Paddick conformity (CI) and gradient (GI) index and by V12 and mean dose to the brain-minus-PTV, and in terms of MU and overall treatment time (OTT) per fraction. OTT was measured for HA treatments, whereas for RA plans OTT was estimated by assuming 3 min. For initial patient setup plus 5 min. For each CBCT-guided setup correction per isocenter.ResultsSignificant variations in favour of HA plans were computed for both target dose indexes, CI (p < .01) and GI (p < .01). The lower GI in HA plans was the likely cause of the significant reduction in V12 to the brain-minus-PTV (p = .023). Although at low doses, below 2–5 Gy, the sparing of the brain-minus-PTV was in favour of RA plans, no significant difference in terms of mean doses to the brain-minus-PTV was observed between the two groups (p = .31). Finally, both MU (p < .01) and OTT (p < .01) were significantly reduced by HyperArc plans.ConclusionsFor linac-based SRS/FSRT of multiple brain lesions, HyperArc plans assured a higher CI and a lower GI than standard multiple-isocenter VMAT plans. This is consistent with the computed reduction in V12 to the brain-minus-PTV. Finally, HyperArc treatments were completed within a typical 20 min. time slot, with a significant time reduction with respect to the expected duration of multiple-isocenters VMAT.

The impact of adjuvant chemoradiotherapy timing on survival of head and neck cancers.

Delays in postoperative head and neck (HN) radiotherapy have been associated with decreased overall survival; however, the impact of delays in postoperative HN chemoradiotherapy remains undefined. All patients with nonmetastatic HN cancer (oral cavity, oropharynx, larynx, hypopharynx) who underwent curative intent surgery and received adjuvant chemoradiotherapy were identified from the National Cancer Database (2005-2012). Overall treatment time (OTT) was defined as the time from surgery to the end of radiation therapy. Statistical methods included Cox proportional hazards modeling, which adjusted for clinicopathologic, demographic, and socioeconomic factors. Recursive partitioning analysis (RPA) identified the optimal threshold of OTT via conditional inference trees to estimate the greatest differences in overall survival (OS) on the basis of randomly selected training and validation sets. A total of 16,733 patients were included, with a median follow-up of 37 months. Median OS for OTT in a predefined threshold of ≤ 13 weeks was 10.1 years (95% confidence interval [CI], 9.8 years; not reached) compared with 8.7 years (95% CI, 8.2-9.2 years) in > 13 weeks. On multivariate analysis, OTT of > 13 weeks versus ≤ 13 weeks independently increased mortality risk (hazard ratio, 1.10; 95% CI, 1.04-1.17; P = < 0.001). RPA identified an optimal OTT threshold of 97 days (interquartile range: 96-98 days). The OTT threshold of 97 days was confirmed in a full Cox regression model estimating the risk of death according to overall treatment time as a continuous variable. In this large hospital-based national data, an OTT of greater than approximately 14 weeks most consistently increased the risk of death. 4. Laryngoscope, 128:2326-2332, 2018.

Hyperthermic isolated limb perfusion, preoperative radiotherapy, and surgery (PRS) a new limb saving treatment strategy for locally advanced sarcomas.

This feasibility study presents the results of a new intensive treatment regimen for locally advanced extremity soft tissue sarcomas (ESTS), consisting of hyperthermic isolated limb perfusion (HILP), preoperative external beam radiotherapy (EBRT), and surgical resection. From 2011 to 2016, 11 high grade locally advanced ESTS patients underwent this treatment regimen. Preoperative EBRT (12 × 3 Gy) started <4 weeks following the HILP (TNF-α and melphalan) and the surgical resection was planned to take place <2 weeks following the end of the EBRT. All patients completed the treatment. After a median follow-up of 32 (23-50) months, the limb was saved in 10 patients (91%), 1 patient (9%) developed a local recurrence, 5 patients (45%) developed distant metastases, and 3 patients (27%) died of their disease. During follow-up two patients (18%) developed a pathologic fracture of the treated limb and three patients (27%) developed a major wound complication requiring surgical intervention. The median overall treatment time (OTT) was 56 (49-69) days. This intensive treatment regimen is feasible and safe in locally advanced ESTS, and it achieves oncological results that are comparable with conventional HILP treatment. In addition, the major wound complication risk is comparable and the OTT is reduced.

Efficacy and tolerance of high-dose-rate brachytherapy boost after external radiotherapy in the treatment of squamous cell carcinoma of the anal canal.

PurposeThe aim of this study was to evaluate the efficacy and toxicity of high-dose-rate brachytherapy (HDR-BT) boost in anal squamous cell carcinoma (ASCC).Material and methodsThis was a monocentric retrospective study involving patients treated by external irradiation (± chemotherapy), with HDR-BT boost, for a localized ASCC. Clinical evaluation was performed every six months. Oncological results were analyzed with: local relapse-free survival (LRFS), colostomy-free survival (CFS), metastatic-free survival (MFS), disease-free survival (DFS), and overall survival (OS). Acute and late toxicities were collected (CTCV4.0) and LENT/SOMA score was performed.ResultsFrom May 2005 to January 2018, 46 patients (pts) were analyzed. The median follow-up was 61 months (10-145 months), the median age was 65 years (34-84 years), with a sex ratio M/F = 0.24. The TNM classification was as follows: T1 – 13 pts (21.7%), T2 – 34 pts (73.9%), T3 – 2 pts (4.3%), N+ – 6 pts (13.1%). External beam radiotherapy (EBRT) delivered a median dose of 45 Gy (36-50.4 Gy) in 25 fractions, and HDR-BT 12 Gy (10-18 Gy) in 3 fractions. The median overall treatment time (OTT) was 58 days (41-101 days), with a median EBRT/brachytherapy interval of 17 days (4-60 days). Oncological findings showed 5-year rates of LRFS 81.2%, MFS 88.7%, DFS 70%, and OS 90%. All abdominoperineal amputations were performed in case of local relapse (4 pts, 8.7%), leading to a 5-year CFS of 79.5%. Acute urinary toxicities were frequent (G1 41.3%, G2 4.3%). The acute digestive toxicities were: G1 71.7%, G2 6.5%, and G3 2.2%. The late urinary toxicities were: G1 4.3%, G2 2.2%, and G3 2.2%. Late digestive toxicities were: G1 56.5%, G2 8.7%, G3 2.2%, and G4 2.2%.ConclusionsIn ASCC management, HDR-BT boost appears to be a treatment with a long-term acceptable toxicity profile, shorter than EBRT boost, with a reduction of side effects.

Digestive toxicities after palliative three-dimensional conformal radiation therapy (3D-CRT) for cervico-thoracic spinal metastases.

The palliative treatment for cervico-thoracic spinal metastases is based on a three-dimensional conformal radiation therapy (3D-CRT). Digestive toxicities are common and cause a clinical impact frequently underestimated in patients. We performed a retrospective study of digestive side effects occurring after palliative 3D-CRT for cervico-thoracic spinal metastases. All patients receiving palliative 3D-CRT at Jean Bernard Center from January 2013 to December 2014 for spinal metastases between the 5th cervical vertebra (C5) and the 12th thoracic vertebra (T12) were eligible. Three-dimensional conformal RT was delivered by a linear accelerator (CLINAC, Varian). Premedication to prevent digestive toxicities was not used. Adverse events ("esophagitis" and "nausea and/or vomiting") were evaluated according to the NCI-CTCae (version 4). From January 2013 to December 2014, 128 patients met the study criteria. The median age was 68.6years [31.8; 88.6]. Most patients (84.4%) received 30Gy in 10 fractions. The median overall time of treatment was 13days [3-33]. Forty patients (31.3%) suffered from grade ≥ 2 of "esophagitis" (35 grade 2 (27.4%) and 5 grade 3 (3.9%)). Eight patients (6.3%) suffered from grade ≥ 2 of "nausea and/or vomiting" (6 grade 2 (4.7%), 1 grade 3 (0.8%), and 1 grade 4 (0.8%)). The high incidence of moderate to severe digestive toxicities after palliative 3D-CRT for cervico-thoracic spinal metastases led to consider static or dynamic intensity-modulated radiation therapy (IMRT) to reduce the dose to organ at risk (the esophagus and stomach). Dosimetric studies and implementation in the clinic should be the next steps.

PORTAF \u2013 postoperative radiotherapy of non-small cell lung cancer: accelerated versus conventional fractionation \u2013 study protocol for a randomized controlled trial

BackgroundIn early-stage non-small cell lung cancer (NSCLC) without affected lymph nodes detected at staging, surgical resection is still the mainstay of treatment. However, in patients with metastatic mediastinal lymph nodes (pN2) or non-radically resected primary tumors (R1/R2), postoperative radiotherapy (possibly combined with chemotherapy) is indicated. So far, investigations about time factors affecting postoperative radiotherapy have only examined the waiting time defined as interval between surgery and start of radiotherapy, but not the overall treatment time (OTT) itself. Conversely, results from trials on primary radio(chemo)therapy in NSCLC show that longer OTT correlates with significantly worse local tumor control and overall survival rates. This time factor of primary radio(chemo)therapy is thought to mainly be based on repopulation of surviving tumor cells between irradiation fractions. It remains to be elucidated if such an effect also occurs when patients with NSCLC are treated with postoperative radiotherapy after surgery (and chemotherapy). Our own retrospective data suggest an advantage of shorter OTT also for postoperative radiotherapy in this patient group.Methods/designThis is a multicenter, prospective randomized trial investigating whether an accelerated course of postoperative radiotherapy with photons or protons (7 fractions per week, 2 Gy fractions) improves locoregional tumor control in NSCLC patients in comparison to conventional fractionation (5 fractions per week, 2 Gy fractions). Target volumes and total radiation doses will be stratified in both treatment arms based on individual risk factors.DiscussionFor the primary endpoint of the study we postulate an increase in local tumor control from 70% to 85% after 36 months. Secondary endpoints are overall survival of patients; local recurrence-free and distant metastases-free survival after 36 months; acute and late toxicity and quality of life for both treatment methods.Trial registrationClinicalTrials.gov, NCT02189967. Registered on 22 May 2014.

Clinical outcomes using image-guided interstitial brachytherapy for definitive cervical cancer patients with high-risk clinical target volumes greater than 30 cc

PurposeGiven the limited data using an interstitial approach with 3D-based planning for definitive cervical cancer utilizing the GEC-ESTRO defined high-risk clinical target volume (HR-CTV), we reviewed our institutional experience of cervical cancer patients with HR-CTVs ≥ 30 cc to determine whether our clinical and toxicity outcomes are acceptable. MethodsA retrospective review of 37 cervical cancer patients with high-risk clinical target volumes (HR-CTVs) ≥30 cc treated with interstitial image-guided brachytherapy (IS IGBT) was performed. All patients received external beam radiotherapy to a median dose of 45 Gy, followed by IS IGBT delivered in a single implant to a median dose of 6 Gy × 5 fractions. Median HR-CTV was 59 cc. A median HR-CTV D90 of 87.44 Gy was achieved. Kaplan–Meier method was used to evaluate local control (LC), distant control, and overall survival (OS), with stratification by overall treatment time (OTT) ≤ 7 or >7 weeks. ResultsMedian followup was 17 months. The estimated 2-year LC, distant control, and OS were 77.6% (confidence interval [CI]: 63.8–94.5%), 56.8% (CI: 41.3–78.1%), and 54.4% (CI: 39.4–75%), respectively. The 2-year LC for OTT ≤7 weeks and >7 weeks were 100% and 58.3%, respectively (p = 0.026). The 2-year OS for OTT ≤7 weeks and >7 weeks were 77.8% and 38%, respectively (p = 0.021). DiscussionsIS IGBT can achieve a high D90 to the HR-CTV even in the setting of large-volume disease and results in a favorable LC and toxicity profile. OTT > 7 weeks is associated with significant decrease in LC and OS. ConclusionsEfforts should be made to complete whole treatment within 7 weeks as this is associated with improved clinical outcomes.

The prognostic impact of overall treatment time on disease outcome in uterine cervical cancer patients treated primarily with concomitant chemoradiotherapy: a nationwide Taiwanese cohort study

The importance of the overall treatment time (OTT) has a paradoxical status in the current era of concomitant chemoradiotherapy. The main objective of this nationwide study was to evaluate the correlation between overall treatment duration and clinical outcome in cervical cancer patients treated primarily with curative concurrent chemoradiotherapy (CCRT). In this population-based cohort study, 2,594 patients diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage I-IVA uterine cervical cancer were studied. Univariate and multivariate analyses of prognostic factors were analyzed using Cox’s proportional hazards models. The median irradiation duration was 59 days. Significant prognostic factors related to poor cancer-specific survival (CSS) and overall survival (OS) included old age, non-squamous cell cancer type, high-grade histology, increased tumor size, advanced FIGO stage, and prolonged OTT. After multivariate analysis, prolonged treatment time remained as a significant factor for poor CSS (hazard ratio, HR = 1.33; p < 0.001) and OS (HR = 1.15; p = 0.05). Further subgroup analysis showed that the 5-year OS rates after a treatment time of ≤ 56 days compared with > 56 days in patients with FIGO stages I-IIB and III-IVA were 70% and 65% (p = 0.002) compared with 43% and 42% (p = 0.67), respectively. Inconclusion, completion of CCRT within 8 weeks is recommended, particularly for patients with FIGO stage I-IIB disease.

The influence of overall treatment time to the efficiency of chemo-radiotherapy for locally advanced cervical cancer

AbstractPurposeThis study aims to clarify the influence of overall treatment time (OTT) on the efficiency of combined chemo-radiotherapy in cervical cancer.Material and methodsThis retrospective study enrolled 122 cervical cancer patients who had squamous cell carcinoma and had undergone definitive chemo-radiotherapy from 2009 to 2013. All patients received whole pelvic radiotherapy (WPRT) with the dose of 50 Gy in 25 fractions (with central shielding after 44 Gy) plus intracavitary brachytherapy with the dose of 28 Gy in four fractions. During WPRT, all patients received concurrent chemotherapy with weekly platinum-based regimen. The data of patient characteristics, OTT, treatment results and toxicities were collected and evaluated.ResultsThe mean follow-up time was 36 months. The mean age of patients was 52 years old; 68% of patients were stage IIB related to International Federation of Gynaecology and Obstetrics staging. Pelvic control (PC), distant metastasis-free survival (DMFS), disease-free survival (DFS) and overall survival (OS) rates did not differ significantly in the data-derived cut points of 55·8 and 53 days. No statistically significant difference in treatment results between the two groups of OTT&lt;49 and OTT≥62 days was observed.ConclusionsIn our data-derived cut point, OTT did not influence to PC, DMFS, DFS and OS. The influence of OTT on treatment results may be found in longer periods.

Prolonged Overall Treatment Time and Lack of Skin Rash Negatively Impact Overall Survival in Locally Advanced Head and Neck Cancer Patients Treated with Radiotherapy and Concomitant Cetuximab.

Cetuximab, a chimeric monoclonal antibody against EGFR sensitizes tumors to radiotherapy (RT), but is associated with skin and mucosal toxicity. We report outcomes and tolerance of definitive RT in association with cetuximab in patients with locally advanced squamous cell carcinoma (LASCC) of the head and neck. Between 2006 and 2011, 92 consecutive patients with LASCC of the head and neck were treated with RT and concomitant weekly cetuximab. Median age was 61.7years. Most patients presented with oropharyngeal tumors (52.2%) and stage IV disease (77.2%). Sixty-nine patients received at least 7cycles of cetuximab. Cetuximab was stopped at the first infusion following allergic reactions in four patients. During RT, 37% of patients developed grade≥3 dermatitis; grade≥2 cetuximab-induced rash occurred in 43 patients (46.7%). Severe mucositis (grade≥3) affected 57.6% of patients. Ten percent of patients did not receive the full course of RT, and temporary discontinuation due to acute toxicity was frequent and affected 37 patients (53%). The median RT overall treatment time (OTT) in patients with interrupted RT was 56days (47-75) compared to 51days (47-65) in patients who did not require toxicity-related radiation interruptions (p<0.05). After a median follow-up of 17.5months (1.3-107.6) for all patients, median overall survival was 17.9months (95% CI: 12.7-23.2), and loco-regional control (LRC) was 9.2months (95% CI: 3.9-14.4). On multivariate analysis, hemoglobin concentration and occurrence of rash grade≥2 were independent prognostic factors for LRC (p=0.023 and p=0.006, respectively). Lack of rash and extended OTT negatively impacted overall survival (p=0.048 and 0.052, respectively). Skin and mucosal toxicity remains an issue in patients with LASCC of the head and neck treated with concomitant cetuximab and RT. Severe toxicity leads to treatment interruptions and prolonged overall treatment time, with consequent decreased overall survival in these patients.