Subjective, Objective, Management, Analytic Research Articles

EQD2 Analyses of Vaginal Complications in Exclusive Brachytherapy for Postoperative Endometrial Carcinoma.

Simple SummaryVaginal complications in exclusive vaginal-cuff brachytherapy (EVCBT) have not been analyzed in terms of the dose received by a vaginal volume of 2 cm3. The aim of this work was to analyze the vaginal dose and complications in EVCBT. In the present analysis, we found that all the patients receiving < 68Gy equivalent dose 2Gy/day at 2 cm3 of the most exposed area to the dose of the vagina only developed G0–G1 and 1G2 without vaginal stenosis complications and without relapses. This dose limit could eliminate G2 vaginal stenosis and is the hypothesis of a new analysis in our center.Background: To evaluate whether EQD2(α/β = 3Gy) at 2 cm3 of the most exposed area of the vagina is related to late vaginal toxicity in postoperative endometrial cancer (PEC) patients (p) treated with exclusive brachytherapy (BT). Methods: From 2014 to 2017, 43p were included in this study. BT was administered: 3-fractions of 6Gy in 37p and 2-fractions of 7.5Gy in 6p. The dose was prescribed at a depth of 5 mm from the applicator surface with dose-point optimization based on distance. The active treatment length was 2.5 cm. CTV-D90 and the dose to the most exposed 2 cm3 of the vagina was calculated for each patient. Late toxicity of the bladder and rectum was assessed using Radiation Therapy Oncology Group (RTOG) criteria, and vaginal toxicity by objective Late Effects Normal Tissue Task Force (LENT)-Subjective, Objective, Management, Analytic (SOMA) (LENT-SOMA) criteria. Statistics: frequency tables, mean, median, range, standard deviation, and box plot. Results: The median follow-up was 51 months (12–68). 20 p (46.5%) and 2 p (4.7%) developed G1 and G2 vaginal complications, respectively. Only 1/2 p-G2 receiving EQD2(α/β = 3Gy) at 2 cm3 >68Gy presented vaginal shortening and 18/20 p-G1 received doses < 68Gy. Conclusions: PECp receiving exclusive brachytherapy with doses < 68Gy EQD2(α/β = 3Gy) at 2 cm2 of the vagina presented only G0–G1 vaginal toxicity, except for one with bleeding telangiectasias. Larger prospective studies are necessary to confirm the present results.

Effect of Tumor Size and Tumor Location in the Breast on Late Cosmetic Outcomes in Patients with Early-Stage Breast Cancer Who Underwent Breast-Conserving Surgery and Intraoperative Boost Radiotherapy

This study aimed to investigate whether tumor size and tumor location in the breast affected cosmetic outcomes and late radiation toxicity in early-stage breast cancer patients who underwent breast conserving surgery and intraoperative radiotherapy as boost. This case series analysis study was based on records in the patient files and included 103 patients with breast cancer. Patients were scored using the Late Effects Normal Tissue Task Force (LENT)-Subjective, Objective, Management, Analytic (SOMA) scale. The effect of tumor size and tumor location on cosmetic outcomes was analyzed using one-way analysis of variance. The median duration of follow-up was 51 (24–78) months. Based on the LENT-SOMA scale, 40 (38.8%) women were grade 0, 42 (40.7%) grade 1, 18 (17.5%) grade 2, and 3 (2.9%) grade 3. The median tumor diameter of the patients was 16 for grade 0, 19 for grade 1, 23, for grade 2, and 25 for grade 3, respectively. Tumor locations in patients scored as grades 2 and 3 were mostly in inner quadrants, whereas those scored as grades 0 and 1 were similar in all quadrants. The effect of tumor size on cosmetic outcomes was statistically significant (p = 0.0001), whereas that of tumor location was no effect on result (p > 0.05). Radiotoxicity and cosmetic outcome in the late period may be related to tumor size and applicator diameter. Although patients with tumors located in the upper outer quadrant had better cosmetic outcomes, tumor location in the breast on the cosmesis was insignificant.

Randomized, Placebo-Controlled Clinical Trial Combining Pentoxifylline-Tocopherol and Clodronate in the Treatment of Radiation-Induced Plexopathy

Radiation-induced (RI) plexopathy is a rare peripheral nerve injury after radiation therapy for cancer. No treatment has been shown to slow its progression. A pentoxifylline-vitamin E combination significantly reduced RI fibrosis, and its association with clodronate (PENTOCLO) allowed healing of osteoradionecrosis and reduction of neurologic symptoms in phase 2 trials. A placebo-controlled, double-blind trial conducted in adults with RI limb plexopathy without cancer recurrence, randomized in 2 arms to PENTOCLO (pentoxifylline 800 mg, tocopherol 1000 mg, clodronate 1600 mg 5 days per week) or triple placebo. The primary outcome measure after 18 months of treatment was the neurologic Subjective Objective Management Analytic (SOMA) score evaluating pain, paresthesia, and motor disability. Between 2011 and 2015, 59 patients were included: 1 false inclusion (neoplastic plexopathy), 29 treated with placebo (group P), and 29 treated with the active drugs (group A); 46 patients presented an upper-limb and 12 a lower-limb plexopathy. The mean delay after irradiation was 26 ± 8 years, for patients with neurologic symptoms for 5 ± 5 years. The median global SOMA scores in the P and A groups, respectively, were 9 (range, 6-11) versus 9 (range, 8-11) at M0 and 9 (range, 5-12) versus 10 (range, 6-11) at M18 without any significant difference. Analysis of thesecondary outcomes showed that SOMA score subdomains for pain and paresthesia were more affected in group A (not significant). The frequency of adverse events was similar in the 2 groups (81% of patients): slight expected vascular-gastrointestinal symptoms in A, but a large excess of RI complications (arterial stenosis). This first randomized drug trial in RI plexopathy failed to show a beneficial effect. More studies are needed in patients with less advanced disease and fewer confounding comorbidities and with a more sensitive measure to detect a therapeutic effect.

Comparison between high-dose and low-dose intravenous methylprednisolone therapy in patients with brain necrosis after radiotherapy for nasopharyngeal carcinoma

BackgroundRadiotherapy is the standard radical treatment for nasopharyngeal carcinoma (NPC) and may cause radiation-induced brain necrosis (RN). Intravenous steroids have been considered as an effective treatment for RN. However, evidence concerning the efficacy of different doses of intravenous steroid therapy remains insufficient to establish the optimal regimen for NPC patients with RN. MethodsWe retrospectively reviewed charts of 169 patients who were diagnosed with RN after radiotherapy for NPC, treated with low-dose or high-dose intravenous methylprednisolone (IVMP) and followed up for 12 months. We collected the clinical data, including the Late Effects of Normal Tissue (LENT)/Subjective, Objective, Management, Analytic (SOMA) scales score and Montreal Cognitive Assessment (MoCA) score. Magnetic resonance imaging (MRI) was performed pre- and post-treatment to define the radiographic response. ResultsThere were no significant differences in the treatment response based on MRI, or changes in clinical symptoms and cognitive function between low and high-dose groups. Thirty of 93 low-dose patients (32.3%) and 21 of 76 high-dose patients (27.6%) presented effective response in MRI, with no significant differences between groups (P = 0.515). Neither group showed a significant difference in the effective rate based on the MoCA total score and LENT/SOMA score. The most commonly reported grade 3 adverse events in the high-dose group (n = 76) were infections and infestations (3 [3.9%] vs. none for low-dose group). ConclusionsWe found low-dose IVMP was not inferior to high-dose IVMP for NPC patients with RN. In addition, treatment-related infections and infestations were likewise more common with high-dose steroid than low-dose steroid.

Dosimetric Inhomogeneity Predicts for Long-Term Breast Pain Following Breast-Conserving Therapy

The objective of this cross-sectional questionnaire study was to characterize long-term breast pain in patients undergoing breast conserving surgery and radiation (BCT) and to identify predictors of this pain. We identified 355 eligible patients with Tis-T2, N0, M0 breast cancer who underwent BCT in 2007-2011, without recurrent disease. Patients with invasive disease were required to have a negative sentinel lymph node biopsy with ≤5 nodes removed. Patients who received radiation therapy (RT) with a separate nodal field, high tangents, partial breast plan, or prone positioning and those who received chemotherapy were excluded. A questionnaire with 10 items derived from the Late Effects Normal Tissue Task Force (LENT)-Subjective, Objective, Management, Analytic (SOMA) scale detailing the severity, frequency, duration, and impact of pain or discomfort in the treated breast over the previous 2 weeks was mailed to all eligible women. A logistic regression model was built to identify predictors of long-term breast pain based on survey results and patient, disease, and treatment data. Questionnaire response rate was 80% (N = 285). Median time from RT was 50.3 months. A total of 135 patients (47%) reported pain in the treated breast; 19 (14%) had pain constantly or at least daily, and 15 (11%) had intense pain. Pain interfered with daily activities in 11 patients (8%), with 6 (4%) taking analgesics for this pain. Fourteen (10%) reported that the pain affected their quality of life. Ninety-three (69%) noted their pain had been present for at least 1 year. Sixty-eight (50%) reported that the pain was not changing with time, while 16 (12%) stated that the pain was getting worse. On univariable analysis, volume of breast tissue treated to ≥105% of the prescribed dose (OR = 1.001 per cc, 95% CI = 1.000-1.002; p = 0.045), volume of breast tissue treated to ≥110% of the prescribed dose (OR = 1.009 per cc, 95% CI = 1.002-1.016; p = 0.012) and hormone therapy (OR = 1.98, 95% CI = 1.13-3.48; p = 0.02) predicted for long-term breast pain. There was no impact of hypofractionation (n = 41). On multivariable analysis, volume ≥110% (OR = 1.01 per cc, 95% CI = 1.003-1.017; p = 0.007), shorter time since treatment (OR = 0.98, 95% CI = 0.96-0.997; p = 0.03) and hormone therapy (OR = 1.91, 95% CI = 1.08-3.40; p = 0.03) were independent predictors of pain. Volume ≥105% was not included in the multivariable model with volume >110% due to a high degree of collinearity, but was also independently associated with breast pain in a model with time since treatment and hormone therapy. Long-term breast pain was common after BCT. While nearly half of patients had pain, most considered it tolerable. Dosimetric inhomogeneity independently predicted for pain and should be minimized to the greatest extent possible.

Dosimetric Inhomogeneity Predicts for Long-Term Breast Pain After Breast-Conserving Therapy

The objective of this cross-sectional study was to characterize long-term breast pain in patients undergoing breast-conserving surgery and radiation (BCT) and to identify predictors of this pain. We identified 355 eligible patients with Tis-T2N0M0 breast cancer who underwent BCT in 2007 to 2011, without recurrent disease. A questionnaire derived from the Late Effects Normal Tissue Task Force (LENT) Subjective, Objective, Management, Analytic (SOMA) scale was mailed with 7 items detailing the severity, frequency, duration, and impact of ipsilateral breast pain over the previous 2 weeks. A logistic regression model identified predictors of long-term breast pain based on questionnaire responses and patient, disease, and treatment characteristics. The questionnaire response rate was 80% (n=285). One hundred thirty-five patients (47%) reported pain in the treated breast, with 19 (14%) having pain constantly or at least daily; 15 (11%) had intense pain. The pain interfered with daily activities in 11 patients (8%). Six patients (4%) took analgesics for breast pain. Fourteen (10%) thought that the pain affected their quality of life. On univariable analysis, volume of breast tissue treated to ≥105% of the prescribed dose (odds ratio [OR] 1.001 per cc, 95% confidence interval [CI] 1.000-1.002; P=.045), volume treated to ≥110% (OR 1.009 per cc, 95% CI 1.002-1.016; P=.012), hormone therapy use (OR 1.95, 95% CI 1.12-3.39; P=.02), and other sites of pain (OR 1.79, 95% CI 1.05-3.07; P=.03) predicted for long-term breast pain. On multivariable analysis, volume ≥110% (OR 1.01 per cc, 95% CI 1.003-1.017; P=.007), shorter time since treatment (OR 0.98 per month, 95% CI 0.96-0.998; P=.03), and hormone therapy (OR 1.84, 95% CI 1.05-3.25; P=.03) were independent predictors of pain. Long-term breast pain was common after BCT. Although nearly half of patients had pain, most considered it tolerable. Dosimetric inhomogeneity independently predicted for pain and should be minimized to the greatest extent possible.

The Efficacy of the Combination Therapy with Oral and Topical Mesalazine for Patients with the First Episode of Radiation Proctitis

Radiation proctitis is a common complication of pelvic radiation for which an optimal treatment remains undetermined. We assessed the efficacy of oral and topical mesalazine combination therapy for patients with naive radiation proctitis. A total of 23 patients with radiation proctitis were enrolled in the study over a period of 2 years. Three of these patients were excluded due to severe bleeding during the study. Twenty patients (mean age 60.3 years; two males, 18 females) were treated with oral mesalazine (3 × 1 g per day) plus a daily mesalazine suppository (1 g per day at bedtime) for 4 weeks. The efficacy of treatment was assessed according to the Subjective Objective Management Analytic (SOMA) scale for alleviation of clinical symptoms of rectal toxicity and sigmoidoscopic findings. The mean bleeding score improved significantly from 2.10 to 1.70 (p = 0.002) with mesalazine treatment. However, scores were not improved for pain (0.30-0.20, p = 0.163), tenesmus (0.50-0.45, p = 0.577), or stool frequency (0.35-0.30, p = 0.577). The improvements in the mean telangiectasia score (1.80-1.45, p = 0.005), bleeding point score (1.60-1.05, p < 0.001), and friable mucosa score (1.35-1.00, p = 0.005) were all statistically significant. No side-effects were noted in any of the patients. The combination of oral and topical mesalazine therapy for radiation proctitis may be a safe and effective treatment for naive radiation proctitis, especially for hemorrhagic proctitis. A large, randomized controlled trial is required to confirm the results of this pilot study.

Subjective and objective measures of late genitourinary morbidity following hypofractionated radiotherapy in men with prostate cancer

To value the late genitourinary (GU) morbidity in men treated with a hypofractionated radiotherapy regimen for prostate cancer. Patients with intermediate risk factors according to D'Amico's criteria were selected. The hypofractionated schedule consisted of 15 fractions of 3.63 Gy delivered three times per week for a total dose of 54.3 Gy. Significant changes in storage-symptoms were not found. A significant transient worsening in the score of late effects of normal tissue late effects normal tissue task force (LENT)-subjective, objective, management, analytic (SOMA) urinary-function domain was observed at 12 months with subsequent improvement at 28 months. The assessment of voiding-symptoms and maximum urinary flow rate (Qmax) showed that no significant difference was measurable at 12 and 28 months. For PVR, a transient increase at 12 months with a subsequent decrease at 28 months was measured. No significant increase in alpha-blockers usage and in the percentage of men with pathological nonintubated uroflowmetry (NIF) was observed at 12 and 28 months. Finally, patients did not perceive any clinical worsening in their quality of life (QoL) as attested by the International Prostate Symptom Score (IPSS)-QoL. Our study seems to suggest that our hypofractionated radiotherapy schedule for the treatment of prostate cancer is safe in terms of late urinary morbidity. Further study will be required to confirm our results.

Dose–volume modeling of salivary function in patients with head-and-neck cancer receiving radiotherapy

We investigated the factors that affect salivary function after head-and-neck radiotherapy (RT), including parotid gland dose-volume effects, potential compensation by less-irradiated gland tissue, and functional recovery over time. Sixty-five patients with head-and-neck tumors were enrolled in a prospective salivary function study. RT was delivered using intensity-modulated RT (n = 45), forward-planning three-dimensional conformal RT (n = 14), or three-dimensional conformal RT with an intensity-modulated RT boost (n = 6). Whole salivary flow was measured before therapy and at 6 months (n = 61) and 12 months (n = 31) after RT. A wide variety of dose-volume models to predict post-RT salivary function were tested. Xerostomia was defined according to the subjective, objective, management, analytic (SOMA) criteria as occurring when posttreatment salivary function was < 25% of the pretreatment function. Multivariate logistic regression analysis was used to assess the combined effect of dose-volume, patient-, and treatment-related factors. A significant correlation was observed between the relative quality-of-life scores and relative stimulated saliva values at 6 months after RT (Spearman's correlation coefficient [R(s)] = 0.46, p < 0.001). The dose-volume factors were by far the strongest correlates with stimulated saliva flow, although other factors showed modest significance in multimetric models (chemotherapy, gender, and Karnofsky performance status). Several fitted dose-volume models provided a good mathematical description of the data. Significant noise in the salivary measurements (repeated measurement coefficient of variation was 27% in normal subjects) precluded selection of any one of the models presented solely on the basis of the objective fit criteria. Nevertheless, the mean dose-exponential model, in which each parotid gland's relative salivary gland function equaled exp(-A x mean gland dose), with A equal to 0.054/Gy (68% confidence interval 0.052-0.059), provided a good representation of the data and was incorporated into our multimetric analysis. Using that model, we estimated that a mean parotid dose of 25.8 Gy, on average, was likely to reduce a single parotid gland's flow to 25% of its pretreatment value, regardless of the treatment delivery method. Significant correlations were observed between a logistic multivariate model (incorporating the mean dose-exponential equation, gender, and Karnofsky performance status) and stimulated saliva flow at 6 months (R(s) = 0.73), stimulated saliva flow at 12 months (R(s) = 0.54), and quality-of-life score at 6 months (R(s) = 0.35) after RT. Stimulated parotid salivary gland dose-volume models strongly correlated with both stimulated salivary function and quality-of-life scores at 6 months after RT. The mean stimulated saliva flow rates improved from 6 to 12 months after RT. Salivary function, in each gland, appeared to be lost exponentially at a rate of approximately 5%/1 Gy of mean dose. Additional research is necessary to distinguish among the models for use in treatment planning. The incidence of xerostomia was significantly decreased when the mean dose of at least one parotid gland was kept to < 25.8 Gy with conventional fractionation. However, even lower mean doses imply increased late salivary function.

Assessment of morbidity in carcinoma of the cervix: a comparison of the LENT SOMA scales and the Franco-Italian glossary

Background and purpose: To assess the correlation between the LENT (late effects on normal tissue) SOMA (subjective objective management analytic) system and the Franco-Italian glossary scores of late morbidity in cervical cancer patients treated with radiation, and to compare the ability of the scoring systems to detect differences between radiation treatment groups. Materials and methods: The study was retrospective. Patients, invited to take part in the study, had radiotherapy for cervical cancer and had a minimum of 3 years follow-up with no evidence of recurrence. One hundred patients agreed to take part. LENT subjective data were obtained using a patient questionnaire approach in order to complete the scales as published. The LENT objective, management and Franco-Italian glossary scores were obtained by a physician. Correlations between scores and differences between treatment groups were examined using non-parametric tests. Results: The average LENT SOMA scores had a greater resolution than the maximum scores, and using the maximum score alone underestimated treatment morbidity. The Franco-Italian glossary scores correlated strongly with the LENT objective scores ( ρ=0.61, P<0.0005), and less strongly with the LENT subjective scores ( ρ=0.45, P<0.0005). Significant differences in morbidity between the radiation treatment groups were measured using both the LENT SOMA system and the Franco-Italian glossary. Conclusions: The maximum and average LENT scores should be reported for each subsite. The LENT objective scores correlated well with the scores obtained using the established Franco-Italian glossary, but the LENT system provided additional information on subjective treatment effects. Both systems were able to measure significant differences in morbidity between radiation treatment groups. In conclusion, the LENT SOMA system is a valid and comprehensive approach for scoring the late normal tissue effects of radiotherapy.

Evaluation of the LENT-SOMA scales for the prospective assessment of treatment morbidity in cervical carcinoma

Purpose To examine the Late Effects Normal Tissue Task Force (LENT)-Subjective, Objective, Management, Analytic (SOMA) scales prospectively in carcinoma of the cervix treated curatively with radiotherapy (RT) using interviews and postal questionnaires and to test the sensitivity of the scales in assessing the radiation effects. Methods and materials A consecutive series of 100 patients completed questionnaires to score the subjective part of the published LENT-SOMA scales. Assessments were made before RT and at approximately 21, 70, 200, 400, 600, and 800 days after the start of treatment. The acceptability and feasibility of using the scales was examined using compliance in completion of the questionnaires. The scales were validated by evaluating the concordance of data obtained by two independent scorers and by examining the ability of the scales to measure radiation-related symptoms. Results Questionnaires were completed for 89 patients before RT. The level of noncompliance was 11%. The concordance between scores when two people completed the questionnaires independently was excellent. Subjective subsite scores were highest 21 days after treatment but generally fell by 70 days. The average baseline overall LENT-SOMA subjective scores increased with advancing stage ( p = 0.008) and were higher for patients treated with RT alone ( p = 0.044). Conclusion In cervical carcinoma, the LENT-SOMA scales were acceptable and feasible to administer in the clinic and appropriate in the measurement of early subjective morbidity from RT.