Intensity-modulated Radiotherapy In Patients Research Articles

Updated Analysis of Comparative Toxicity of Proton and Photon Radiation for Prostate Cancer.

Previous comparative effectiveness studies have not demonstrated a benefit of proton beam therapy (PBT) compared with intensity-modulated radiation therapy (IMRT) for prostate cancer. An updated comparison of GI and genitourinary (GU) toxicity is needed. We investigated the SEER-Medicare linked database, identifying patients with localized prostate cancer diagnosed from 2010 to 2017. Procedure and diagnosis codes indicative of treatment-related toxicity were identified. As a sensitivity analysis, we also identified toxicity based only on procedure codes. Patients who underwent IMRT and PBT were matched 2:1 on the basis of clinical and sociodemographic characteristics. We then compared GI and GU toxicity at 6, 12, and 24 months after treatment. The final sample included 772 PBT patients matched to 1,544 IMRT patients. The frequency of GI toxicity for IMRT versus PBT was 3.5% versus 2.5% at 6 months (P = .18), 9.5% versus 10.2% at 12 months (P = .18), and 20.5% versus 23.4% at 24 months (P = .11). The frequency of only procedure codes indicative of GI toxicity for IMRT versus PBT was too low to be reported and not significantly different. The frequency of GU toxicity for IMRT versus PBT was 6.8% versus 5.7% (P = .30), 14.3% versus 12.2% (P = .13), and 28.2% versus 25.8% (P = .21) at 6, 12, and 24 months, respectively. When looking only at procedure codes, the frequency of GU toxicity for IMRT was 1.0% at 6 months, whereas it was too infrequent to report for PBT (P = .64). GU toxicity for IMRT versus PBT was 3.3% versus 2.1% (P = .10), and 8.7% versus 6.7% (P = .10) at 12 and 24 months, respectively. In this observational study, there were no statistically significant differences between PBT and IMRT in terms of GI or GU toxicity.

The potential overdose of heart and left anterior descending coronary artery region during intensity-modulated radiation therapy in patients with esophageal cancer.

This study aimed to investigate the changes in dose distribution in the heart and left anterior descending coronary artery region (LADR) during intensity-modulated radiation therapy (IMRT) in patients with esophageal cancer (EC) treated at our institution. The heart and LADR were delineated on the initial and off-cord boost planning computed tomography (CT) images. Cardiac volume reduction (CVR) was defined as the reduction in cardiac volume between the initial CT and off-cord boost CT at the dose of 36Gy irradiated. The involved field IMRT plan was created based on each initial and off-cord boost CT image and was analyzed based on the relationship between CVR and heart and LADR dose-volume parameters (Heart-Dmax, Heart-Dmean, Heart-V20, Heart-V30, Heart-V40, LADR-Dmax, LADR-Dmean, LADR-V15 and LADR-V30). Forty patients with EC were investigated between January 2016 and January 2022. The median CVR ratio during radiation therapy (RT) was 5.57% (range, -7.79 to 18.26%). Simple linear regression analysis revealed significant correlations between CVR during RT and changes in the heart and LADR dose-volume parameters. Some patients (>10%) experienced severe changes in the heart and LADR dose distribution. In three cases with reduced heart volume and primary tumor mass, the changes in LADR-V15 and LADR-V30 showed outliers. In conclusion, CVR during RT correlated with an increase in the heart and LADR dose. When both CVR and tumor volume reduction are large, a potential overdose of LADR during RT should be noted in the IMRT era.

Dosiomics for intensity-modulated radiotherapy in patients with prostate cancer: survival analysis stratified by baseline prostate-specific antigen and Gleason grade group in a 2-institutional retrospective study.

This study evaluated the prognostic impact of the quality of dose distribution using dosiomics in patients with prostate cancer, stratified by pretreatment prostate-specific antigen (PSA) levels and Gleason grade (GG) group. A total of 721 patients (Japanese Foundation for Cancer Research [JFCR] cohort: N = 489 and Tokyo Radiation Oncology Clinic [TROC] cohort: N = 232) with localized prostate cancer treated by intensity-modulated radiation therapy were enrolled. Two predictive dosiomic features for biochemical recurrence (BCR) were selected and patients were divided into certain groups stratified by pretreatment PSA levels and GG. Freedom from biochemical failure (FFBF) was estimated using the Kaplan-Meier method based on each dosiomic feature and univariate discrimination was evaluated using the log-rank test. As an exploratory analysis, a dosiomics hazard (DH) score was developed and its prognostic power for BCR was examined. The dosiomic feature extracted from planning target volume (PTV) significantly distinguished the high- and low-risk groups in patients with PSA levels >10 ng/mL (7-year FFBF: 86.7% vs 76.1%, P < .01), GG 4 (92.2% vs 76.9%, P < .01), and GG 5 (83.1% vs 77.8%, P = .04). The DH score showed significant association with BCR (hazard score: 2.04; 95% confidence interval: 1.38-3.01; P < .001). The quality of planned dose distribution on PTV may affect the prognosis of patients with poor prognostic factors, such as PSA levels >10 ng/mL and higher GGs. The effects of planned dose distribution on prognosis differ depending on the patient's clinical background.

A Comparison of 3D Conformal and Deep Inspiratory Breath Holding vs. 4D-CT Intensity-Modulated Radiation Therapy for Patients with Left Breast Cancer.

Multimodality is required for the treatment of breast cancer. Surgery, radiation (RT), and systemic therapy were traditionally used. Pharmacotherapy includes different drug mechanisms, such as chemotherapy, hormone therapy, and targeted therapies, alone or in combination with radiotherapy. While radiation offers numerous benefits, it also has certain harmful risks. such as cardiac and pulmonary toxicity, lymphedema, and secondary cancer. Modern radiation techniques have been developed to reduce organs at risk (OAR) doses. This study is a prospective feasibility trial conducted at the Fayium Oncology Center on patients with left breast cancer receiving adjuvant locoregional radiotherapy after either breast conservative surgery (BCS) or modified radical mastectomy (MRM). This study aimed to assess the proportion of patients who are fit both physically and intellectually to undergo breast radiotherapy using the deep inspiratory breath-holding (DIBH) technique, comparing different dosimetric outcomes between the 3D dimensional conformal with DIBH and 4D-CT IMRT plans of the same patient. D95 of the clinical target volume (CTV) of the target is significantly higher in the 3D DIBH plan than in the IMRT plan, with an average of 90.812% vs. 86.944%. The dosimetry of the mean heart dose (MHD) in the 4D-CT IMRT plan was significantly lower than in the 3D conformal with the DIBH plan (2.6224 vs. 4.056 Gy, p < 0.0064), and no significant difference between the two plans regarding mean left anterior descending artery (LAD) (14.696 vs. 13.492 Gy, p < 0.58), maximum LAD (39.9 vs. 43.5 Gy, p < 0.35), and V20 of the ipsilateral lung (18.66% vs. 16.306%, p < 0.88) was observed. Internal mammary chain (IMC) irradiation was better in the 4D-CT IMRT plan. Radiotherapy of the breast and chest wall with the 4D-CT IMRT technique appears not to be inferior to the 3D conformal with the DIBH technique and can be used as an alternative to the 3D conformal with the DIBH technique in patients meeting the exclusion criteria for performing the DIBH maneuver concerning coverage to target volumes or unacceptably high doses to OAR.

The feasibility of level Ib-sparing intensity-modulated radiation therapy in patients with nasopharyngeal carcinoma and high-risk factors classified based on the International Guideline

Background and PurposeTo examine the feasibility of level Ib-sparing intensity-modulated radiation therapy (IMRT) in patients with nasopharyngeal carcinoma (NPC) who had high-risk factors classified based on the International Guideline (IG). Materials and MethodsWe evaluated 961 non-metastatic NPC cases based on IG recommendations for prophylactic Ib irradiation. Four high-risk factors were used to categorise patients into three cohorts: A, B, and C. Propensity score matching was used to balance baseline characteristics in Cohort C, resulting in a matched Cohort C. Recurrence rates at level Ib and regional relapse-free survival (RRFS) rates were evaluated. ResultsAmong patients with negative Ib lymph nodes (LNs), 18, 54, 420, and 444 exhibited involvement of structures that drain to level Ib as the first echelon (FES), involvement of the submandibular gland (SMG), level II LNs with radiologic extranodal extension (rENE), and level II nodes with a maximal axial diameter (MAD) ≥ 2 cm, respectively. The recurrence rate was highest in Cohort A (11.1 %). Cohort B had no level Ib recurrence. In matched Cohort C, recurrence rates were low in both groups (Ib-sparing group: 0.6 % vs. Ib-covering group: 0.6 %, P > 0.999). No significant differences were observed in 5-year RRFS rates between the two groups in cohort A (p = 0.208), cohort B (p = 0.905), and matched cohort C (p = 0.423). ConclusionsLevel Ib-sparing IMRT could be performed safely for NPC patients with level II LNs who had rENE and/or MAD ≥ 2 cm. Further research should determine the necessity of level Ib prophylactic irradiation for patients with FES or SMG involvement.

Long-term outcomes of stimulated salivary flow and xerostomia after definitive intensity-modulated radiation therapy for patients with head and neck cancer†.

This retrospective study aimed to evaluate the time to recovery from xerostomia and analyze its predictors, along with long-term outcomes of stimulated salivary flow after intensity-modulated radiation therapy (IMRT) for head and neck cancer (HNC). We evaluated patients with HNC who had received IMRT with curative intent between 2012 and 2018 at our institution. The salivary recovery ratio (SRR) was defined as '(the stimulated salivary flow)/(pre-treatment salivary flow)'. The cutoff value of SRR in salivary recovery was estimated via the relationship between SRR and xerostomia grades. The salivary recovery time was defined as the time for SRR to exceed cutoff values from the end of radiotherapy. Fifty-seven patients were analyzed, with a 48-month median follow-up period of stimulated salivary flow. The cutoff value for SRR was 44.8%, and patients with a higher grade of xerostomia had a lower SRR (P < 0.001). The median salivary recovery time was 12months. The cumulative incidence rates of salivary recovery at two and four years were 84 (95% confidence interval [CI]: 53-79) and 92% (95% CI: 82-97), respectively, and these were significantly lower in patients with a higher mean parotid gland dose, mean oral cavity dose and stimulated salivary flow per parotid gland volume. Stimulated salivary flow and xerostomia recover over a long period after radiotherapy.

Clinical Efficacy and Complications of Intensity-modulated Radiation Therapy in Patients With Oropharyngeal Carcinoma: Especially Focus On Osteoradionecrosis

We explored the relative clinical efficacy of intensity-modulated radiation therapy (IMRT) in patients with oropharyngeal cancer (OPC) compared with three-dimensional conformal radiation therapy (3D-CRT). Seventy-four OPC patients treated with definitive IMRT or 3D-CRT between May 2010 and December 2018 were analyzed. Of these, 42 patients were treated with IMRT and 32 with 3D-CRT. We compared clinical benefits and complications. Particular attention was focused on osteoradionecrosis (ORN), which is the most problematic radiation late adverse event, and evaluated the irradiated mandibular volumes. There was no significant difference in the 3-year overall survival (OS), progression free survival (PFS) and locoregional control (LRC) rates between the two groups. However, late Grade 2 xerostomia was lower in the IMRT groups. Four patients (19.0%) developed Grade 3, while no patients developed ORN in the IMRT group (P = 0.003). A comparison of the mandible volumes between the two groups showed that the IMRT group had lower mandibular volumes than the 3D-CRT group in the high-dose range of V40, V50, V60 and V70. In addition, a comparison of the mandibular volumes between ORN and non-ORN showed a significant difference in the V60 and V70. ORN incidence was higher in V60 ≥ 25% and V70 ≥ 15%. A comparison of IMRT and 3D-CRT showed no significant difference in outcomes, however, IMRT led to a significant reduction in late xerostomia and ORN in OPC patients. Reducing of the mandibular V60 and V70 by IMRT seemed to reduce the risk of ORN.

Standardizing LT Chest Wall Radiotherapy Treatment Planning in a Low- or Middle- Income Country Radiotherapy Clinic Using Knowledge Based Planning

Radiotherapy departments in low- or middle-income countries (LMICs) tend to lag behind introducing emerging technologies like intensity-modulated radiotherapy (IMRT). IMRT has become the standard of care in high-income countries (HIC) due to reduced toxicity and improved outcomes in a wide variety of cancers. The purpose of this work is showing the results of left Chest-Wall knowledge-based planning (KBP) standardization and implementation in a LMIC setting. A Halcyon Linac was installed at our clinic in Guatemala in 2019 and currently used to treat ∼90 IMRT patients daily. The standardization of IMRT procedures has been difficult for complex sites like chest-wall. The steps for standardization included: AAPM TG-263 nomenclature implementation, and planning workflows within the TPS, creation of optimization structures, and plan quality evaluation following RTOG1005 protocol hypofractionation arm. 25 plans were created manually achieving all RTOG1005 protocol constraints. The statistics were analyzed trough the model analytics tool provided by KPB manufacturer. The results show that more plans are needed to improve the KBP model. This initial model was used to create a standardized clinical protocol in the TPS in order to continue adding plans to the KBP model database. This approach ensures that we obtain consistent plan quality and standardize our planning. The manual planning objectives achieved: CONCLUSION: The experience using the TPS to standardize our treatment planning process achieved good consistency in our planning objectives. This approach will help create KBP models according to our own clinic-specific requirements. Future work will be made to compare our LMIC KBP models with those made at a HIC academic radiotherapy center.

Dysphagia-optimised intensity-modulated radiotherapy versus standard intensity-modulated radiotherapy in patients with head and neck cancer (DARS): a phase 3, multicentre, randomised, controlled trial

Most newly diagnosed oropharyngeal and hypopharyngeal cancers are treated with chemoradiotherapy with curative intent but at the consequence of adverse effects on quality of life. We aimed to investigate if dysphagia-optimised intensity-modulated radiotherapy (DO-IMRT) reduced radiation dose to the dysphagia and aspiration related structures and improved swallowing function compared with standard IMRT. DARS was a parallel-group, phase 3, multicentre, randomised, controlled trial done in 22 radiotherapy centres in Ireland and the UK. Participants were aged 18 years and older, had T1-4, N0-3, M0 oropharyngeal or hypopharyngeal cancer, a WHO performance status of 0 or 1, and no pre-existing swallowing dysfunction. Participants were centrally randomly assigned (1:1) using a minimisation algorithm (balancing factors: centre, chemotherapy use, tumour type, American Joint Committee on Cancer tumour stage) to receive DO-IMRT or standard IMRT. Participants and speech language therapists were masked to treatment allocation. Radiotherapy was given in 30 fractions over 6 weeks. Dose was 65 Gy to primary and nodal tumour and 54 Gy to remaining pharyngeal subsite and nodal areas at risk of microscopic disease. For DO-IMRT, the volume of the superior and middle pharyngeal constrictor muscle or inferior pharyngeal constrictor muscle lying outside the high-dose target volume had a mandatory 50 Gy mean dose constraint. The primary endpoint was MD Anderson Dysphagia Inventory (MDADI) composite score 12 months after radiotherapy, analysed in the modified intention-to-treat population that included only patients who completed a 12-month assessment; safety was assessed in all randomly assigned patients who received at least one fraction of radiotherapy. The study is registered with the ISRCTN registry, ISRCTN25458988, and is complete. From June 24, 2016, to April 27, 2018, 118 patients were registered, 112 of whom were randomly assigned (56 to each treatment group). 22 (20%) participants were female and 90 (80%) were male; median age was 57 years (IQR 52-62). Median follow-up was 39·5 months (IQR 37·8-50·0). Patients in the DO-IMRT group had significantly higher MDADI composite scores at 12 months than patients in the standard IMRT group (mean score 77·7 [SD 16·1] vs 70·6 [17·3]; mean difference 7·2 [95% CI 0·4-13·9]; p=0·037). 25 serious adverse events (16 serious adverse events assessed as unrelated to study treatment [nine in the DO-IMRT group and seven in the standard IMRT group] and nine serious adverse reactions [two vs seven]) were reported in 23 patients. The most common grade 3-4 late adverse events were hearing impairment (nine [16%] of 55 in the DO-IMRT group vs seven [13%] of 55 in the standard IMRT group), dry mouth (three [5%] vs eight [15%]), and dysphagia (three [5%] vs eight [15%]). There were no treatment-related deaths. Our findings suggest that DO-IMRT improves patient-reported swallowing function compared with standard IMRT. DO-IMRT should be considered a new standard of care for patients receiving radiotherapy for pharyngeal cancers. Cancer Research UK.

Ninety-degree angled collimator: a dosimetric study related to dynamic intensity-modulated radiotherapy in patients with endometrial carcinoma

BackgroundOur purpose was to ensure that the dose constraints of the organs at risk (OARs) were not exceeded while increasing the prescription dose to the planning target volume (PTV) from 45 to 50.4 Gray (Gy) with the dynamic intensity-modulated radiotherapy (IMRT) technique. While trying for this purpose, a new dynamic IMRT technique named 90° angled collimated dynamic IMRT (A-IMRT) planning was developed by us.MethodsThis study was based on the computed tomography data sets of 20 patients with postoperatively diagnosed International Federation of Gynecology and Obstetrics stage 2 endometrial carcinoma. For each patient, conventional dynamic IMRT (C-IMRT, collimator angle of 0° at all gantry angles), A-IMRT (collimator angle of 90° at gantry angles of 110°, 180°, 215°, and 285°), and volumetric modulated arc therapy (VMAT) were planned. Planning techniques were compared with parameters used to evaluate PTV and OARs via dose-volume-histogram analysis using the paired two-tailed Wilcoxon’s signed-rank test; p < 0.05 was considered indicative of statistical significance.ResultsAll plans achieved adequate dose coverage for PTV. Although the technique with the lowest mean conformality index was A-IMRT (0.76 ± 0.05) compared to both C-IMRT (0.79 ± 0.04, p = 0.000) and VMAT (0.83 ± 0.03, p = 0.000), it protected the OARs especially the bladder (V45 = 32.84 ± 2.03 vs. 44.21 ± 6.67, p = 0.000), rectum (V30 = 56.18 ± 2.05 vs. 73.80 ± 4.75, p = 0.000) and both femoral heads (V30 for right = 12.19 ± 1.34 vs. 21.42 ± 4.03, p = 0.000 and V30 for left = 12.58 ± 1.48 vs. 21.35 ± 4.16, p = 0.000) better than C-IMRT. While the dose constraints of the bladder, rectum and bilateral femoral heads were not exceeded in any patient with A-IMRT or VMAT, they were exceeded in 19 (95%), 20 (100%) and 20 (100%) patients with C-IMRT, respectively.ConclusionsOARs are better protected when external beam radiotherapy is applied to the pelvis at a dose of 50.4 Gy by turning the collimator angle to 90° at some gantry angles with the dynamic IMRT technique in the absence of VMAT.

Uncertainty and influencing factors of the placement error of three-dimensional conformal intensity-modulated radiotherapy for thoracic tumors.

Radiation therapy is an important method for the treatment of chest tumors. This study discussed the placement error of three-dimensional (3D) conformal intensity-modulated radiotherapy in patients with different types of chest tumors and analyzed the relevant influencing factors. 100 patients with chest tumors diagnosed and treated in our hospital from March 2016 to March 2018 were randomly selected as research subjects, including 42 cases of esophageal cancer, 44 cases of breast cancer, and 14 cases of lung cancer. All patients underwent 3D conformal radiotherapy. The setup errors of patients with esophageal cancer, breast cancer, and lung cancer were detected after 3D conformal radiotherapy. Besides, the influencing factors of 3D conformal for thoracic tumors were analyzed by multiple linear regression analysis. After 3D conformal radiotherapy, the systematic errors of patients with esophageal cancer in X-axis, Y-axis, and Z-axis were -0.10, 1.26 and 0.07, respectively, while the random errors in X-axis, Y-axis, and Z-axis were 1.18, -1.14, and 0.97 respectively. The times for the absolute values of the positioning error with a range of ≤5 mm in X-axis, Y-axis, and Z-axis were 40 (95.24%), 2 (4.76%) and 36 (85.71%), while these with a range of >5 mm in X-axis, Y-axis, and Z-axis were 6 (14.29%), 41 (97.62%) and 1 (2.38%), respectively. For patients with breast cancer, the systematic errors and random errors in X-axis, Y-axis, and Z-axis are -0.19, 1.19, and 0.15, as well as 0.97, 0.02 and 1.29, respectively. The times for the absolute values of the positioning error with a range of ≤5 mm and >5 mm were 41 (93.18%), 3 (6.82%), and 36 (81.82%), as well as 8 (18.18%), 42 (95.45%) and 2 (4.55%), severally. For patients with lung cancer, the systematic errors and random errors in X-axis, Y-axis, and Z-axis were 0.14, 1.42, and 0.15, as well as 1.35, -0.23 and 1.12, respectively. The times for the absolute values of the positioning error with the range of ≤5 mm and >5 mm were 14 (93.33%), 1 (6.67%), and 11 (73.33%), as well as 4 (26.67%), 14 (93.33%) and 1 (6.67%) after 3D conformal radiotherapy. After multiple linear regression analyses, gender and lung volume were the influencing factors of Z-axis setup error, and the lesion location was the influence factor of Y-axis setup error (p<0.05). There are certain positioning errors in the X-axis, Y-axis, and Z-axis directions of thoracic tumors receiving 3D conformal radiotherapy. Gender, lung volume, and lesion location are all important factors that affect the placement error. The results of this study provide a certain reference for the positioning error of radiation therapy for thoracic tumors, which is conducive to improving the accuracy of radiotherapy and better protecting the surrounding tissues.

Hyperfractionation compared with standard fractionation in intensity-modulated radiotherapy for patients with locally advanced recurrent nasopharyngeal carcinoma: a multicentre, randomised, open-label, phase 3 trial

Reirradiation in standard fractionation for locally advanced recurrent nasopharyngeal carcinoma after a previous course of high-dose radiotherapy is often associated with substantial late toxicity, negating its overall benefit. We therefore aimed to investigate the efficacy and safety of hyperfractionation compared with standard fractionation in intensity-modulated radiotherapy. This multicentre, randomised, open-label, phase 3 trial was done in three centres in Guangzhou, China. Eligible patients were aged 18-65 years with histopathologically confirmed undifferentiated or differentiated, non-keratinising, advanced locally recurrent nasopharyngeal carcinoma. Participants were randomly assigned (1:1) to either receive hyperfractionation (65 Gy in 54 fractions, given twice daily with an interfractional time interval of at least 6 h) or standard fractionation (60 Gy in 27 fractions, given once a day). Intensity-modulated radiotherapy was used in both groups. A computer program generated the assignment sequence and randomisation was stratified by treatment centre, recurrent tumour stage (T2-T3 vs T4), and recurrent nodal stage (N0 vs N1-N2), determined at the time of randomisation. The two primary endpoints were the incidence of severe late complications defined as the incidence of grade 3 or worse late radiation-induced complications occurring 3 months after the completion of radiotherapy until the latest follow-up in the safety population, and overall survival defined as the time interval from randomisation to death due to any cause in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02456506. Between July 10, 2015, and Dec 23, 2019, 178 patients were screened for eligibility, 144 of whom were enrolled and randomly assigned to hyperfractionation or standard fractionation (n=72 in each group). 35 (24%) participants were women and 109 (76%) were men. After a median follow-up of 45·0 months (IQR 37·3-53·3), there was a significantly lower incidence of grade 3 or worse late radiation-induced toxicity in the hyperfractionation group (23 [34%] of 68 patients) versus the standard fractionation group (39 [57%] of 68 patients; between-group difference -23% [95% CI -39 to -7]; p=0·023). Patients in the hyperfractionation group had better 3-year overall survival than those in the standard fractionation group (74·6% [95% CI 64·4 to 84·8] vs 55·0% [43·4 to 66·6]; hazard ratio for death 0·54 [95% CI 0·33 to 0·88]; p=0·014). There were fewer grade 5 late complications in the hyperfractionation group (five [7%] nasal haemorrhage) than in the standard fractionation group (16 [24%], including two [3%] nasopharyngeal necrosis, 11 [16%] nasal haemorrhage, and three [4%] temporal lobe necrosis). Hyperfractionated intensity-modulated radiotherapy could significantly decrease the rate of severe late complications and improve overall survival among patients with locally advanced recurrent nasopharyngeal carcinoma. Our findings suggest that hyperfractionated intensity-modulated radiotherapy could be used as the standard of care for these patients. Key-Area Research and Development of Guangdong Province, the National Natural Science Foundation of China, the Special Support Program for High-level Talents in Sun Yat-sen University Cancer Center, the Guangzhou Science and Technology Plan Project, and the National Ten Thousand Talents Program Science and Technology Innovation Leading Talents, Sun Yat-Sen University Clinical Research 5010 Program.

Toxicity and efficacy of stereotactic body radiation therapy vs. intensity-modulated radiation therapy for the treatment of locally advanced pancreatic cancer in a phase 3 trial.

713 Background: Locally advanced pancreatic cancer (LAPC) remains one of the deadliest cancers. Radiation is listed as a first line therapy option in treatment guidelines and remains a common treatment for this patient population primarily for local disease control and symptoms. Herein, we performed an exploratory analysis to compare the toxicity and efficacy between patients receiving either stereotactic body radiation therapy (SBRT) or intensity-modulated radiation therapy (IMRT) during the induction phase (prior to randomization) of a Phase 3 trial for localized intra-arterial gemcitabine therapy. Methods: As part of the TIGeR-PaC Phase 3 trial, patients with LAPC and an ECOG of 0-1 underwent an induction phase and were treated with 2 cycles of gemcitabine and nab-paclitaxel prior to receiving SBRT (n=59; 33Gy in 5 Fractions) or IMRT (n=75; 50Gy in 25 fractions) with concurrent PO capecitabine BID Monday-Friday. We performed Mann-Whitney analyses to compare mean percent changes in tumor size (imaging performed prior and 1-month after radiation) and CA 19-9 tumor markers. Adverse event (AE) incidence data during and 2 weeks after completion of the last fraction of radiation was used to compare toxicity via a contingency table. Results: A total of 134 patients across 22 sites (63 male/71 female; median age: 68.5 years) underwent radiation with no significant difference in baseline demographics between SBRT and IMRT patients. The decision for SBRT vs. IMRT was site-driven and not pre-specified by the protocol. Of these, 104 had analyzable imaging data, 50 SBRT and 54 IMRT, with a mean baseline tumor size of 4.3 cm and 4.0 cm (p=0.17), respectively. Pancreatic tumor location included head (n=63), body (n=36), or other (n=5). There was no statistical significance between the mean percent change of tumor size between SBRT (-13.3%) and IMRT (-10.8%; p=0.834). Both arms had similar RECIST partial response (approximately 18% of patients) after treatment. Patients with analyzable CA 19-9 tumor marker data (14 SBRT, 17 IMRT) showed no significant difference in percent change (mean, 9.8%±111%, -40.7%±40%; p=0.262). The SBRT subgroup had significantly less patients drop-out due to clinical deterioration (1 SBRT, 9 IMRT; p=0.025) and experience any AE (26 SBRT, 49 IMRT; p=0.014), gastrointestinal AE (10 SBRT, 33 IMRT; p&lt;0.001), grade 3 or higher AE (6 SBRT, 20 IMRT; p=0.017), and serious AE (2 SBRT, 10 IMRT; p=0.045) p=0.014, 0.017, 0.045, respectively). The main AEs and serious AEs were gastrointestinal events. Conclusions: When compared to IMRT, SBRT demonstrates improved tolerability for treatment of patients with LAPC with comparable clinical efficacy. Clinical trial information: NCT03257033 .

Cox Regression Analysis of Prognostic Factors of Intensity-Modulated Radiotherapy in Patients with Bladder Cancer.

This paper aims to explore the prognostic factors of intensity-modulated radiotherapy (IMRT) in patients with bladder cancer by Cox regression analysis and to provide evidence for prolonging the survival of patients and improving the treatment status. A total of 153 cases of patients with bladder cancer who received IMRT were selected as research objects, and their clinical data were retrospectively analyzed and followed up. Kaplan-Meier survival analysis was conducted to calculate the median survival period, univariate and multivariate Cox regression were used to analyze the prognostic factors of IMRT in patients with bladder cancer, and receiver operating characteristic curve was adopted to evaluate the prediction efficiency of influencing factors. Patients were followed up for 9-40 months, and 55 patients died by the end of the follow-up. The median survival time was 30 months, and the 3-year survival rate was 64.05% (98/153). Univariate analysis showed that T stage, total cystectomy, lymph node, pathological type and hydronephrosis influenced the prognosis of IMRT for patients with bladder cancer (p < 0.05). Multivariate Cox regression analysis showed T3 stage (odds ratio (OR) = 0.149, 0.068-0.327), T4 stage (OR = 27.639, 3.677-207.758), lymph node presence (OR = 0.152, 0.050-0.467), pathological type (OR = 0.086, 0.025-0.296) and hydronephrosis (OR = 7.402, 1.161-47.192) were independent factors affecting the prognosis of IMRT in patients with bladder cancer (p < 0.05), while total cystectomy (OR = 1.037, 0.171-6.301) was not an independent factor affecting the prognosis of IMRT in patients with bladder cancer (p > 0.05). T stage, lymph nodes, nontransitional cell carcinoma with pathological type and hydronephrosis can influence the prognostic effect of IMRT in patients with bladder cancer.

Image-guided intensity-modulated radiotherapy in patients with FIGO IIIC1 cervical cancer: efficacy, toxicity and prognosis.

Background: To investigate the efficacy, toxicity and prognosis of image-guided intensity-modulated radiotherapy (IG-IMRT) in patients with FIGO IIIC1 cervical cancer. Methods: We retrospectively reviewed clinical records of patients with FIGO IIIC1 cervical cancer treated with definitive IG-IMRT in our institute from January 2008 to December 2017. A dose of 50.4Gy in 28 fractions was prescribed to at least 95% of PCTV, the positive pelvic lymph nodes received a dose of 56-61.6Gy in 28 fractions with simultaneous integrated boost (SIB). Weekly cone beam compute tomography (CBCT) and daily megavoltage CT (MVCT) was performed before treatment. Both 2D brachytherapy and 3D brachytherapy were allowed in our study. Weekly Cisplatin (30-40mg/m2) was the first line regimen for concurrent chemotherapy. Overall survival (OS), disease free survival (DFS), local control (LC) and local regional control (LRC) was calculated with Kaplan-Meier method. Cox proportional hazard model was used to perform univariate and multivariate analyses. Results: A total of 502 patients were enrolled in this study. The median follow-up duration was 42.1 months (range: 2.3-137.3 months). The 3-year and 5-year estimated OS, DFS, LC, LRC were 81.7% and 75.5%, 71.4% and 68.6%, 89.9% and 89.9%, 86.1% and 84.3%, respectively. The incidences of chronic grade 3 or greater gastrointestinal and genitourinary toxicities were 2.7 % and 0.8%, respectively. Pelvic lymph nodes recurrence occurred in 21 patients (4.2%). Advanced T stage was identified as adverse factor for OS and LC. More positive lymph nodes (≥2) were associated with worse OS, DFS and LRC. The cycles of concurrent chemotherapy significantly affected OS, DFS and LRC. Conclusion: For patients with FIGO IIIC1 cervical cancer, IG-IMRT was well tolerated with excellent survivals. T stage and number of positive lymph nodes significantly influenced the survivals indicating the heterogeneity of stage IIIC1 cervical cancer patients. Adequate cycles of chemotherapy (≥4 cycles) was of great value for this group of patients.

Comparison of intensity-modulated radiation therapy (IMRT), 3D conformal proton therapy and intensity-modulated proton therapy (IMPT) for the treatment of metastatic brain cancer.

The purpose of this study has been to compare photon intensity modulated radiation therapy (IMRT) against both conformal and intensity modulated proton therapy (IMPT) plans for metastatic brain cancer. Ten IMRT patients with brain cancer were chosen retrospectively, with prescription doses in the range of 20 to 40 Gy, delivered in 3 to 5 fractions using Varian TrueBeam STx machine. Three proton plans with proton double scattering, single collimation static-IMPT, and energy layer by layer collimation dynamic-IMPT were then generated for the same patients using the Mevion S250 system for conformal plans and the S250i system for IMPT plans. Each plan had respective treatment planning systems that include Brainlab iPlan for IMRT, Varian Eclipse for proton double scattering, and RaySearch Raystation for IMPT. Dosimetric and radiobiologic comparisons were made through dose-volume histogram (DVH) analysis of the target and the organs at risk (OAR); and with parameters of equivalent uniform dose (EUD), tumor control probability (TCP), and normal tissue complication probability (NTCP), respectively. A set of variables α/β ratio, survival fraction, and clonogenic cell density were selected and varied to observe their effect on the abovementioned parameters. Doses were observed to be more homogeneous for patients with brain malignancies with photon IMRT treatments, while dose conformity is improved with proton PBS treatments. Normal tissue is, on average, spared more through both proton treatment options. The minimum doses, closely approximated by dose to 98% of the target volume, are similar across treatment modalities with slight variations.

Influence of radiation treatment technique (IMRT vs. 3D-RT) on acute toxicity and prognostic factors for survival for anal cancer

We compared our institutional experience with intensity-modulated radiotherapy (IMRT) and 3D-conformal radiotherapy (3D-RT) for definitive treatment of primary anal cancer. We performed a single-institution retrospective review of all patients with anal squamous cell carcinoma treated with definitive (chemo) radiotherapy with curative intent from 2004 through 2018. We assessed several prognostic factors in respect to relevant survival endpoints. In addition, acute toxicities were determined and compared between IMRT and 3D-RT patients. This study included 94 patients (58 IMRT, 36 3D-RT). Mean follow up for all patients, for IMRT and 3D-RT patients was 61 months (range 6–176), 46 months (range 6–118), and 85 months (range 6–176), respectively. 5-year overall survival (OS) was 86%, disease-free survival (DFS) was 72%, and colostomy-free survival (CFS) was 75% in the IMRT cohort. In the 3D-RT cohort, OS was 87%, DFS was 71%, and CFS was 81% (all p > 0.05). Male gender and Karnofsky Index (KI) were revealed as independent prognostic factors for 5-year OS (p = 0.017; p = 0.023). UICC stage was an independent prognostic factor for DFS and CFS (p = 0.023; p = 0.042). In addition, the pre-treatment leukocyte count was an independent prognostic factor for CFS (p = 0.042). Acute grade ≥ 3 toxicity was not significantly different between IMRT and 3D-RT patients, but the IMRT cohort had favorable outcomes. This study confirmed IMRT as the primary definitive treatment of anal cancer. With similar survival rates, IMRT had the potential to reduce acute toxicity by sparing organs at risk. Promising prognostic factors such as BMI, KI, and leucocyte and hemoglobin levels should be further investigated.

A Prospective Study of Mucosal Sparing Radiation Therapy in Resected Oropharyngeal Cancer Patients

Our objective was to report the prospective results of mucosal sparing radiation therapy in human papillomavirus-related oropharyngeal squamous cell carcinoma. From March 2016 through May 2019, patients were enrolled in this institutional review board-approved prospective cohort study at a multisite institution. Inclusion criteria included p16+ American Joint Committee on Cancer seventh edition pathologic T1 or T2, N1 to N3, and M0 oropharyngeal cancers. Proton therapy (PT) was delivered to at-risk nodal regions, excluding the primary mucosal site. Secondary to insurance denial for PT, intensity modulated radiation therapy (IMRT) was allowed. European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck Module and Patient-Reported Outcomes Measurement Information System surveys (quality of life [QOL]) and modified barium swallowing impairment profiles (MBSImP) were obtained at baseline before radiation therapy, then 3 and 12 months after radiation therapy. Kaplan-Meier estimates were calculated for time-to-event clinical outcomes, and repeated measures mixed models were used to explore changes in QOL over time. A comparison of QOL and swallowing outcomes with standard-of-care treatment was analyzed. There were 61 evaluable patients with a median follow-up of 38 months (range, 10-64); 44 (72%) were treated with PT and 17 (28%) were treated with IMRT. The 2-year local control, locoregional control, distant metastasis-free survival, and overall survival were 98%, 97%, 98%, and 100%, respectively. There were 6 grade ≥3 events related to treatment. Two IMRT patients required percutaneous endoscopic gastrostomy tube placement during treatment secondary to significant nausea due to dysgeusia. Patients noted significant QOL improvement over time in the pain, swallowing, speech, social eating, social contact, mouth opening, and use of pain medication domains (all P < .02). The MBSImP overall severity score as well as oral and pharyngeal impairment scores showed stability with no significant change over time. For the 44 patients treated with PT, the mean D95 to the primary target was 10.7 Gy (standard deviation=12.5 Gy). Mucosal sparing radiation is well tolerated in select resected human papillomavirus-related oropharyngeal squamous cell carcinoma with a low risk of recurrence at the mucosal primary site, a low rate of percutaneous endoscopic gastrostomy tube placement, and few radiation-related grade ≥3 adverse events.

Patient Reported Quality of Life after Moderately Hypofractionated Proton Beam Therapy or Intensity Modulated Radiation Therapy for Prostate Cancer

<h3>Purpose/Objective(s)</h3> We aim to quantify and compare changes in patient reported quality of life (PRQOL) after moderately hypofractionated (MHF) Proton Beam Therapy (PBT) or Intensity Modulated Radiation Therapy (IMRT) for prostate cancer (PC). <h3>Materials/Methods</h3> This multi-institutional analysis included patients with NCCN low or intermediate risk PC treated at 4 tertiary cancer centers with MHF PBT or IMRT with prospective PRQOL collection. Patients completed International Prostate Symptom Score (IPSS) and Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC) pre-treatment and at 3-to-6-month intervals starting at the end of treatment. EPIC is a questionnaire measuring health related quality of life (HRQOL) domains of genitourinary (GU), gastrointestinal (GI), sexual, and hormonal function. Questions are scored from 0 (no problem) to 4 (big problem). EPIC score of 3 or more was considered a meaningful QOL decrement. IPSS measures GU HRQOL; each question is measured from a score of 0 to 5 with a maximum score of 35. Baseline characteristics were compared with Chi squared and t test for IPSS. Models were limited to long term data, at 12 and 36 months. Generalized linear regression models testing effects of time, treatment, and their interaction were fit via Generalized Estimating Equations, controlling for age, race, and NCCN risk group. <h3>Results</h3> 287 IMRT and 485 PBT patients were included. Intermediate NCCN risk group (81.2 vs. 68.2%; p < 0.001), median age at diagnosis (70 vs 66.9 years; p < 0.001) were higher in the IMRT group. Mean IPSS was slightly worse at baseline in the PBT arm (+0.22; CI, -1.54 – 1.10; p=0.74) and slightly better at 3 years (-0.09; CI, -1.48 – 1.65; p=0.91). On Poisson regression controlling for age, race, and NCCN risk group, PBT IPSS trended worse at 12 months (OR, 1.19; CI, 0.98 - 1.44; p=0.077) without any difference at 36 months (OR, 1.08; CI, 0.80 - 1.26; p=0.94). Similarly, EPIC questionnaire for overall GI function trended worse with PBT at 12 months (CI, 0.83 - 16.27; p=0.085) without difference at 36 months (CI, 0.49 - 12.27, p=0.27). 4.9% and 4.8% patients in the PBT and IMRT arms, respectively, rated their overall GI function at 12 months as a severe problem. Among PBT and IMRT patients combined, severe GU concerns were unlikely at 12 months (GU frequency: 17.5; GU pain: 3.6; stream problem: 11.2%). <h3>Conclusion</h3> PRQOL showed a non-significant trend toward worse 1-year overall GI function and IPSS for PBT; this effect was not present at 3 years. In this multi-institutional, prospective study of PC, long-term GU and GI function was not significantly different between PBT or IMRT arms.

Physician Graded Toxicity Profiles and Survival Outcomes among Patients with Non-Metastatic Oropharyngeal Carcinoma Treated with Proton Therapy vs. Intensity-Modulated Radiation Therapy

<h3>Purpose/Objective(s)</h3> Proton therapy (PT) has a potential advantage over intensity-modulated radiation therapy (IMRT) in the treatment of oropharyngeal carcinoma (OPC) due to reduction of dose to the surrounding organs at risk. Our objective was to compare adverse effects and oncologic outcomes in patients with OPC treated with PT vs. IMRT <h3>Materials/Methods</h3> This retrospective cohort study included 292 consecutive patients with newly diagnosed non-metastatic OPC who received curative-intent radiation with PT or IMRT from 2018 to 2021. Clinical and demographic details were compared between the two groups. The main outcomes were the incidence of acute and chronic treatment-related adverse events (AEs), and oncologic outcomes, including locoregional recurrence (LRR), progression-free survival (PFS), and overall survival (OS). <h3>Results</h3> 58 PT and 234 IMRT patients were included. The median follow-up for all patients was 26 months (2-88mo). Median RT dose was 70 CGE (Gy) (range 66-78 CGE, 64-76 Gy). There were no imbalances in patient/tumor characteristics except for smoking pack-years (PY) (mean 7.4 PYs PT and 13.2Pys IMRT, p=.002), and N-stage (N0 17% PT versus 7% IMRT, N1 5% PT versus 15% IMRT, p=.04). There were no significant differences in T-stage or use of concurrent chemotherapy between PT and IMRT groups. 98% of patients in PT group were p16 or HPV+ versus 92% in the IMRT group. Statistically significant differences were not observed in 3 year overall-survival (91% IMRT, 97% PT, p=0.166), PFS (86% IMRT, 82% PT, p=.984) or LRR (3% IMRT, 5% PT, p=0.369).Using chi-square analysis, acute toxicities were statistically significantly higher for IMRT compared to PT for acute grade ≥2 oral pain (92.8% IMRT vs 72.4%PT p<.001), acute grade ≥2 xerostomia (29 % IMRT versus 21% PT, p<.001), acute grade ≥2 dysgeusia (57% IMRT versus 28% PT, p<.001), grade 3 dysphagia (12% (29) IMRT versus 7% (4) PT p<.001), grade ≥3 mucositis (70% IMRT versus 53% PT, p=.003), grade ≥2 nausea (7.7% IMRT versus 0% PT, p=.04), and grade ≥2 weight loss (59% IMRT, versus 37% PT, p<.001). When excluding patients with follow-up less than 6 months, 221 IMRT and 43 PT patients remain. There were no significant differences in grade ≥2 late toxicities between the two groups. When looking at the presence of any toxicity, at ≥ 6 months follow-up, there was a significant difference in the presence of xerostomia (77% IMRT versus 61% PT, p=.026). Four patients (1.7%) in the IMRT group, versus 1 patient (1.7%) in PT group had a PEG at a follow-up of at least 6 months. All late PEG tubes were due to recurrent/refractory disease <h3>Conclusion</h3> PT for non-metastatic OPC reduces acute toxicity burden in comparison with IMRT with similar oncologic outcomes. Prospective randomized comparisons of these two technologies in the treatment of OPC along with patient-reported outcomes are warranted to confirm our results.