Impact of image-guided radiotherapy to reduce laryngeal edema following treatment for non-laryngeal and non-hypopharyngeal head and neck cancers

We would like to determine the effectiveness of image-guided radiotherapy (IGRT) to reduce laryngeal edema following treatment for head and neck cancer and to assess patient perception of voice and speech after treatment. We conducted a retrospective review of 44 patients undergoing radiation for non-laryngeal and non-hypopharyngeal head and neck cancers. Endoscopic and/or mirror examinations of the larynx were performed following radiotherapy at each follow-up visit. Laryngeal edema was assessed based on the Radiation Therapy Oncology Group grading scale. Patients were also asked to rate about the voice and speech quality relative to their pre-radiotherapy status. The mean laryngeal dose was 16.3 Gy (range: 11.7–45.5 Gy). At a median follow-up of 14 months (range: 2–31 months), three patients (7%) developed laryngeal edema (one grade 1, two grade 2). The mean laryngeal dose was respectively 20.3 Gy in two patients and 20.7 Gy in the third patient developing laryngeal edema. Except for one patient who continued to smoke and drink after radiotherapy, no patient reported any significant change in voice and speech quality after treatment. IGRT results in low rates and low severity of laryngeal edema following treatment for non-laryngeal and non-hypopharyngeal head and neck cancers and may preserve voice quality.     

Three-dimensional conformal radiotherapy for locally advanced (Stage II and worse) head-and-neck cancer: dosimetric and clinical evaluation

PURPOSE: To evaluate the dosimetric parameters of three-dimensional conformal radiotherapy (3D-CRT) in locally advanced head-and-neck tumors (Stage II and above) and the effects on xerostomia. METHODS AND MATERIALS: A total of 49 patients with histologically proven squamous cell cancer of the head and neck were consecutively treated with 3D-CRT using a one-point setup technique; 17 had larynx cancer, 12 oropharynx, 12 oral cavity, and 6 nasopharynx cancer; 2 had other sites of cancer. Of the 49 patients, 41 received postoperative RT and 8 definitive treatment. Also, 13 were treated with cisplatin-based chemotherapy before and during RT; in 6 cases, 5-fluorouracil was added. The follow-up time was 484-567 days (median, 530 days). RESULTS: One-point setup can deliver 96% of the prescribed dose to the isocenter, to the whole planning target volume, including all node levels of the neck and without overdosages. The mean dose to the primary planning target volume was 49.54 +/- 4.82 Gy (51.53 +/- 5.47 Gy for larynx cases). The average dose to the contralateral parotid gland was approximately 38 Gy (30 Gy for larynx cases). The maximal dose to the spinal cord was 46 Gy. A Grade 0 Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer xerostomia score corresponded to a mean dose of 30 Gy to one parotid gland. A lower xerostomia score with a lower mean parotid dose and longer follow-up seemed to give rise to a sort of functional recovery phenomenon. CONCLUSION: Three dimensional-CRT in head-and-neck cancers permits good coverage of the planning target volume with about 10-11 segments and one isocenter. With a mean dose of approximately 30 Gy to the contralateral parotid, we observed no or mild xerostomia.     

Dosimetric and Clinical Predictors of Acute Esophagitis in Lung Cancer Patients in Turkey Treated with Radiotherapy

Background: The purpose of this study was to determine the clinical and dosimetric factors associated withacute esophagitis (AE) in lung cancer patients treated with conformal radiotherapy (RT) in Turkey. Materialsand Methods: In this retrospective review 104 lung cancer patients were examined. Esophagitis grades wereverified weekly during treatment, and at 1 week, and 1 and 2 months afterwards. The clinical parametersincluded patient age, gender, tumor pathology, number of chemotherapy treatments before RT, concurrentchemotherapy, radiation dose, tumor response to RT, tumor localization, interruption of RT, weight loss, tumorand nodal stage and tumor volume. The following dosimetric parameters were analyzed for correlation of AE:The maximum (Dmax) and mean (Dmean) doses delivered to the esophagus, the percentage of esophagus volumereceiving ≥10 Gy (V10), ≥20 Gy (V20), ≥30 Gy (V30), ≥35 Gy (V35), ≥40 Gy (V40), ≥45 Gy (V45), ≥50 Gy (V50) and ≥60Gy (V60). Results: Fifty-five patients (52.9%) developed AE. Maximum grades of AE were recorded: Grade 1 in51 patients (49%), and Grade 2 in 4 patients (3.8%). Clinical factors had no statistically significant influence onthe incidence of AE. In terms of dosimetric findings, correlation analyses demonstrated a significant associationbetween AE and Dmax (>5117 cGy), Dmean (>1487 cGy) and V10-60 (percentage of volume receiving >10 to 60 Gy).The most significant relationship between RT and esophagitis were in Dmax (>5117 cGy) (p=0.002) and percentageof esophageal volume receiving >30 Gy (V30>31%) (p=0.008) in the logistic regression analysis. Conclusions: Themaximum dose esophagus greater than 5117 cGy and approximately one third (31%) of the esophageal volumereceiving >30 Gy was the most statistically significant predictive factor associated with esophagitis due to RT.     

Radiotherapy of carcinoma of the larynx--dose and function preservation

Relationship between irradiated dose and function preservation of the larynx in patients of laryngeal carcinoma (T1-T3) treated with radiotherapy were analysed and discussed. Local control rate for T1 and T2 lesion was highest in the dose range of 65-70 Gy. But in T3 lesion, especially of supraglottic cancer, the dose range to obtain highest local tumor control rate is above 76 Gy and higher than in case of T1 and T2 lesions. Laryngeal edema was seen in patients who were delivered the dose of 80 Gy. But total laryngectomy could be avoided by conservative therapy. Necessity of induction chemotherapy for advanced cases was also discussed.     

Dosimetric Predictors of Dysphonia after Intensity-modulated Radiotherapy for Oropharyngeal Carcinoma

AimsTo investigate dosimetric predictors of voice changes after whole-field intensity-modulated radiotherapy (IMRT).Materials and methodsPatients treated with whole-field IMRT for oropharyngeal/unknown primary tumours were selected for the present retrospective study having grossly uninvolved larynx at the time of radiotherapy and at least one follow-up visit. Voice changes were prospectively scored at each follow-up examination according to the Common Terminology Criteria for Adverse Events (CTCAE) v3.0 scale and self-reported by two items (HN4 and HN10) of the Functional Assessment of Cancer Therapy-Head and Neck Scale (FACT-HN) questionnaire. Predictors of toxicity were investigated at logistic regression, including various patient and tumour characteristics, as well as individual dosimetric data.ResultsWith a median follow-up of 18 months (range 3–46 months), peak CTCAE dysphonia was graded as 2 in 13 patients (10.5%), whereas 45 patients (36.3%) reported peak grade 0–1 voice changes according to FACT-HN4. Communication (FACT-HN10) was barely affected. At multivariate analysis, the mean laryngeal dose was an independent predictor of both grade 2 CTCAE dysphonia (odds ratio = 1.10, 95% confidence interval 1.01–1.20, P = 0.025) and grade 0–1 FACT-HN4 voice changes (odds ratio = 1.11, 95% confidence interval 1.04–1.18, P = 0.001). Further stratification optimised by a receiver operating characteristic (ROC) analysis showed that, to minimise the risk of grade 0–1 FACT-HN4 voice changes, the mean dose to the larynx has to be kept ≤49.4 Gy.ConclusionVoice changes after whole-field IMRT are common, but mild, and are strictly correlated to the dose received by the uninvolved larynx; in order to minimise the risk of side-effects, the mean dose to the larynx should be kept ≤50 Gy.     

Lack of osteoradionecrosis of the mandible after intensity-modulated radiotherapy for head and neck cancer: likely contributions of both dental care and improved dose distributions

PURPOSE: To assess the prevalence and dosimetric and clinical predictors of mandibular osteoradionecrosis (ORN) in patients with head and neck cancer who underwent a pretherapy dental evaluation and prophylactic treatment according to a uniform policy and were treated with intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: Between 1996 and 2005, all patients with head-and-neck cancer treated with parotid gland-sparing IMRT in prospective studies underwent a dental examination and prophylactic treatment according to a uniform policy that included extractions of high-risk, periodontally involved, and nonrestorable teeth in parts of the mandible expected to receive high radiation doses, fluoride supplements, and the placement of guards aiming to reduce electron backscatter off metal teeth restorations. The IMRT plans included dose constraints for the maximal mandibular doses and reduced mean parotid gland and noninvolved oral cavity doses. A retrospective analysis of Grade 2 or worse (clinical) ORN was performed. RESULTS: A total of 176 patients had a minimal follow-up of 6 months. Of these, 31 (17%) had undergone teeth extractions before RT and 13 (7%) after RT. Of the 176 patients, 75% and 50% had received >or=65 Gy and >or=70 Gy to >or=1% of the mandibular volume, respectively. Falloff across the mandible characterized the dose distributions: the average gradient (in the axial plane containing the maximal mandibular dose) was 11 Gy (range, 1-27 Gy; median, 8 Gy). At a median follow-up of 34 months, no cases of ORN had developed (95% confidence interval, 0-2%). CONCLUSION: The use of a strict prophylactic dental care policy and IMRT resulted in no case of clinical ORN. In addition to the dosimetric advantages offered by IMRT, meticulous dental prophylactic care is likely an essential factor in reducing ORN risk.     

Dysphagia and aspiration after chemoradiotherapy for head-and-neck cancer: which anatomic structures are affected and can they be spared by IMRT?

PURPOSE: To identify the anatomic structures whose damage or malfunction cause late dysphagia and aspiration after intensive chemotherapy and radiotherapy (RT) for head-and-neck cancer, and to explore whether they can be spared by intensity-modulated RT (IMRT) without compromising target RT. METHODS AND MATERIALS: A total of 26 patients receiving RT concurrent with gemcitabine, a regimen associated with a high rate of late dysphagia and aspiration, underwent prospective evaluation of swallowing with videofluoroscopy (VF), direct endoscopy, and CT. To assess whether the VF abnormalities were regimen specific, they were compared with the VF findings of 6 patients presenting with dysphagia after RT concurrent with high-dose intra-arterial cisplatin. The anatomic structures whose malfunction was likely to cause each of the VF abnormalities common to both regimens were determined by literature review. Pre- and posttherapy CT scans were reviewed for evidence of posttherapy damage to each of these structures, and those demonstrating posttherapy changes were deemed dysphagia/aspiration-related structures (DARS). Standard three-dimensional (3D) RT, standard IMRT (stIMRT), and dysphagia-optimized IMRT (doIMRT) plans in which sparing of the DARS was included in the optimization cost function, were produced for each of 20 consecutive patients with advanced head-and-neck cancer. RESULTS: The posttherapy VF abnormalities common to both regimens included weakness of the posterior motion of the base of tongue, prolonged pharyngeal transit time, lack of coordination between the swallowing phases, reduced elevation of the larynx, and reduced laryngeal closure and epiglottic inversion, contributing to a high rate of aspiration. The anatomic structures whose malfunction was the likely cause of each of these abnormalities, and that also demonstrated anatomic changes after RT concurrent with gemcitabine doses associated with dysphagia and aspiration, were the pharyngeal constrictor muscles (median thickness near midline 2.5 mm before therapy vs. 7 mm after therapy; p = 0.001), the supraglottic larynx (median thickness, 2 mm before therapy vs. 4 mm after therapy; p < 0.001), and, similarly, the glottic larynx. The constrictors and the glottic and supraglottic larynx were, therefore, deemed the DARS. The lowest maximal dose delivered to a stricture volume was 50 Gy. Reducing the volumes of the DARS receiving > or =50 Gy (V(50)) was, therefore, a planning and evaluation goal. Compared with the 3D plans, stIMRT reduced the V(50) of the pharyngeal constrictors by 10% on average (range, 0-36%, p < 0.001), and doIMRT reduced these volumes further, by an additional 10% on average (range, 0-38%; p <0.001). The V(50) of the larynx (glottic + supraglottic) was reduced marginally by stIMRT compared with 3D (by 7% on average, range, 0-56%; p = 0.054), and doIMRT reduced these volumes by an additional 11%, on average (range, 0-41%; p = 0.002). doIMRT reduced laryngeal V(50) compared with 3D, by 18% on average (range 0-61%; p = 0.001). Certain target delineation rules facilitated sparing of the DARS by IMRT. The maximal DARS doses were not reduced by IMRT because of their partial overlap with the targets. stIMRT and doIMRT did not differ in target doses, parotid gland mean dose, spinal cord, or nonspecified tissue maximal dose. CONCLUSIONS: The structures whose damage may cause dysphagia and aspiration after intensive chemotherapy and RT are the pharyngeal constrictors and the glottic and supraglottic larynx. Compared with 3D-RT, moderate sparing of these structures was achieved by stIMRT, and an additional benefit, whose extent varied among the patients, was gained by doIMRT, without compromising target doses. Clinical validation is required to determine whether the dosimetric gains are translated into clinical ones.     

Dosimetric predictors of radiation esophagitis in patients treated for non-small-cell lung cancer with carboplatin/paclitaxel/radiotherapy

PURPOSE: To establish dosimetric predictors of radiation esophagitis (RE) in patients treated with a combination of carboplatin, paclitaxel, and radiotherapy. METHODS AND MATERIALS: Three-dimensional radiotherapy plans of 26 patients with non-small-cell lung cancer who received 50-60 Gy of radiotherapy concurrently with weekly administration of carboplatin (AUC 2) and paclitaxel (40-45 mg/m(2)) were reviewed in conjunction with RE. The factors analyzed included the following: percentages of organ volumes receiving >40 Gy (V40), >45 Gy (V45), >50 Gy (V50), and >55 Gy (V55); the length of esophagus (total circumference) treated with >40 Gy (LETT40), >45 Gy (LETT45), >50 Gy (LETT50), and >55 Gy (LETT55); the maximum dose in the esophagus (Dmax); and the mean dose in the esophagus (Dmean). Data were obtained on the basis of superposition algorithm. RESULTS: All factors except Dmax showed statistical correlation with RE. Good correlations were shown between RE and LETT45 (rho = 0.714) and V45 (rho = 0.686). CONCLUSIONS: LETT45 and V45 appear to be useful dosimetric predictors of RE. It is also suggested that Dmax does not predict RE.     

Evaluation of larynx-sparing techniques with IMRT when treating the head and neck

PURPOSE: Concern exists that widespread implementation of whole-field intensity-modulated radiotherapy (IMRT) for the treatment of head-and-neck cancer has resulted in increased levels of dysphagia relative to those seen with conventional planning. Other investigators have suggested an alternative junctioned-IMRT (J-IMRT) method, which matches an IMRT plan to a centrally blocked neck field to restrict the laryngeal dose and reduce dysphagia. The effect on target coverage and sparing of organs at risk, including laryngeal sparing, in the optimization was evaluated and compared with that achieved using a J-IMRT technique. METHODS AND MATERIALS: A total of 13 oropharyngeal cancer whole-field IMRT plans were planned with and without including laryngeal sparing in the optimization. A comparison of the target coverage and sparing of organs at risk was made using the resulting dose-volume histograms and dose distribution. The nine plans with disease located superior to the level of the larynx were replanned using a series of J-IMRT techniques to compare the two laryngeal-sparing techniques. RESULTS: An average mean larynx dose of 29.1 Gy was achieved if disease did not extend to the level of the larynx, with 38.8 Gy for disease extending inferiorly and close to the larynx (reduced from 46.2 and 47.7 Gy, respectively, without laryngeal sparing). Additional laryngeal sparing could be achieved with J-IMRT (mean dose 24.4 Gy), although often at the expense of significantly reduced coverage of the target volume and with no improvement to other areas of the IMRT plan. CONCLUSION: The benefits of J-IMRT can be achieved with whole-field IMRT if laryngeal sparing is incorporated into the class solution. Inclusion of laryngeal sparing had no effect on other parameters in the plan.     

Dose de tolérance à l’irradiation des tissus sains : larynx et pharynx

For head and neck cancers, the radiation dose usually needed to sterilize a macroscopic tumour is at least 70 Gy in conventional fractionation. In the larynx, this dose level enables optimal tumour control while exposing the patient to a limited risk of severe complications. For oropharynx and nasopharynx tumors, it is sometimes possible to limit the dose received by the larynx according to the extent of the primary lesion. Thus, if the tumour constraints permit, the maximum dose to the larynx must be less than 63 to 66 Gy. To reduce the risk of laryngeal edema, it is recommended if possible to limit the mean non-involved larynx dose to 40 to 45 Gy. In the pharynx, literature's data suggested to minimize the volume of the pharyngeal constrictor muscles receiving a dose greater than or equal to 60 Gy. Limiting the volume receiving a dose greater than or equal to 50 Gy reduces the risk of dysphagia. These dose constraints should be tailored to each patient taking into account the extent of the initial primary lesion, the possible addition of chemotherapy or a modified fractionation radiotherapy.     

Rectal bleeding after hypofractionated radiotherapy for prostate cancer: correlation between clinical and dosimetric parameters and the incidence of grade 2 or worse rectal bleeding

PURPOSE: To investigate the incidence and severity of rectal bleeding after high-dose hypofractionated radiotherapy (RT) for prostate cancer, and to explore the factors affecting the incidence of Grade 2 or worse rectal bleeding. METHODS AND MATERIALS: The data of 52 patients who had been treated by external beam RT for localized prostate cancer between 1999 and 2002 were analyzed. All the patients had received hypofractionated external beam RT to a total dose of 69 Gy in 3-Gy fractions, three fractions weekly. The clinical and dosimetric factors affecting the incidence of Grade 2 or worse late rectal bleeding were analyzed by univariate and multivariate analyses. The effect of the percentage of the whole rectal volume receiving 30%, 50%, 80%, and 90% of the prescribed radiation dose (V(30), V(50), V(80), and V(90), respectively) on the incidence of rectal bleeding was evaluated. RESULTS: Of the 52 patients, 13 (25%) developed Grade 2 or worse rectal bleeding. One patient who needed laser coagulation and blood transfusion for the treatment of rectal bleeding was classified as having Grade 3 rectal bleeding. The median time to the development of Grade 2 or worse rectal bleeding was 11 months. The results of the univariate analysis revealed that the presence of a history of diabetes mellitus (p < 0.001), and V(30) >/= 60%, V(50) >/= 40% (p < 0.05), V(80) >/= 25%, and V(90) >/= 15% (p < 0.001) were statistically significant risk factors for the occurrence of Grade 2 or worse rectal bleeding. The results of the multivariate analysis revealed that a history of diabetes mellitus was the most statistically significant risk factor for the occurrence of rectal bleeding after hypofractionated RT for prostate cancer (p < 0.05). CONCLUSION: A history of diabetes mellitus was the most statistically significant risk factor for the occurrence of Grade 2 or worse rectal bleeding after high-dose hypofractionated RT, although dosimetric factors were also closely associated with the risk of rectal bleeding.     

Localized volume effects for late rectal and anal toxicity after radiotherapy for prostate cancer

PURPOSE: To identify dosimetric parameters derived from anorectal, rectal, and anal wall dose distributions that correlate with different late gastrointestinal (GI) complications after three-dimensional conformal radiotherapy for prostate cancer. METHODS AND MATERIALS: In this analysis, 641 patients from a randomized trial (68 Gy vs. 78 Gy) were included. Toxicity was scored with adapted Radiation Therapy Oncology Group/European Organization for the Research and Treatment of Cancer (RTOG/EORTC) criteria and five specific complications. The variables derived from dose-volume histogram of anorectal, rectal, and anal wall were as follows: % receiving > or =5-70 Gy (V5-V70), maximum dose (Dmax), and mean dose (D(mean)). The anus was defined as the most caudal 3 cm of the anorectum. Statistics were done with multivariate Cox regression models. Median follow-up was 44 months. RESULTS: Anal dosimetric variables were associated with RTOG/EORTC Grade > or =2 (V5-V40, D(mean)) and incontinence (V5-V70, D(mean)). Bleeding correlated most strongly with anorectal V55-V65, and stool frequency with anorectal V40 and D(mean). Use of steroids was weakly related to anal variables. No volume effect was seen for RTOG/EORTC Grade > or =3 and pain/cramps/tenesmus. CONCLUSION: Different volume effects were found for various late GI complications. Therefore, to evaluate the risk of late GI toxicity, not only intermediate and high doses to the anorectal wall volume should be taken into account, but also the dose to the anal wall.     

The dosimetric impact of supraclavicular nodal irradiation on the thyroid gland in patients with breast cancer

PurposeThe thyroid is not routinely considered an organ at risk in supraclavicular (SC) nodal radiation therapy (RT) for breast cancer. We compared the dosimetric impact of the following 2 RT planning techniques on the thyroid: (1) conventional single anterior field to encompass the SC nodal volume defined clinically; and (2) 3-dimensional conformal radiation therapy (3DCRT) planning to encompass the computed tomography (CT)-contoured SC nodal volume.Methods and MaterialsThe thyroid, SC nodal volumes, and organs at risk were contoured on the planning CT of 20 patients who received 50 Gy in 2-Gy daily fractions to the breast or chest wall, and SC nodes. Comparisons of dosimetric parameters between the techniques were performed: thyroid, mean and maximum dose, V5, V30, and V50 (percentage of thyroid receiving ≥ 5 Gy, ≥ 30 Gy, and ≥ 50 Gy, respectively); SC nodal volume, homogeneity index (HI, percentage volume receiving 95%-107% of prescribed dose); and maximum doses of spinal cord and brachial plexus. Anatomic characteristics that influenced the dose distributions were investigated.ResultsThe 3DCRT planning technique significantly increased all thyroid dosimetric measures (mean dose 17.2 Gy vs 26.7 Gy; maximum dose 48.5 Gy vs 51.9 Gy; V5 45.7% vs 64.9%; V30 33.7% vs 48%; and V50 0.6% vs 26.7%; P < .001). It improved HI for the SC nodal volumes (P < .001) but resulted in higher maximum doses to the spinal cord (6.1 Gy vs 30 Gy) and brachial plexus (43.2 Gy vs 51.4 Gy). The thyroid volume and depth of SC nodes did not influence the thyroid dose distribution. The depth of SC nodes impacted on the HI of SC nodal volumes in the conventional technique (P = .004).ConclusionsThe 3DCRT planning improved dosimetric coverage of the SC nodal volume but increased thyroid radiation doses. The potential adverse effects of incidental thyroid irradiation should be considered while improving dosimetric coverage in SC nodal irradiation for breast cancer.     

Combination of longitudinal and circumferential three-dimensional esophageal dose distribution predicts acute esophagitis in hypofractionated reirradiation of patients with non-small-cell lung cancer treated in stereotactic body frame

PURPOSE: To evaluate dosimetric predictors of acute esophagitis (AE) and clinical outcome of patients with non-small-cell lung cancer (NSCLC) receiving reirradiation. METHODS AND MATERIALS: Seventeen patients with NSCLC received reirradiation to the lung tumors/mediastinum, while immobilized in stereotactic body frame (SBF). CT simulation and hypofractionated three-dimensional radiotherapy were used. Two axial segments of esophagus contours merged together were defined as esophagus disc (ED). For each ED, the percentage (%) of the volume of esophageal circumference treated to % of prescribed dose (PD) was assessed. Number of EDs with 50% or any % of volume (V) of esophageal circumference receiving more than or equal to (>/=) 50%, 80%, and 100% of PD (50% V >/=50% PD; 50% V >/=80% PD; any % V >/=100% PD) were calculated. These dosimetric variables and the length of the esophagus within the radiation therapy (RT) port were correlated with AE using exact Wilcoxon test. RESULTS: A median RT dose was 32 Gy with a median fraction size of 4 Gy. Eleven of 13 patients presenting with pain and/or shortness of breath had complete or partial resolution of symptoms. Median survival time from the start of reirradiation in SBF until death was 5.5 months. AE was observed in 7 patients and resolved within 3 months of RT completion. No Grade 3 or higher events were noticed. The length of the esophagus within RT port did not predict for AE (p = 0.71). However, an increased number of EDs predicted for AE for the following dosimetric variables: 50% V >/=50% PD (p = 0.023), 50% V >/=80% PD (p = 0.047), and any % V >/=100% PD (p = 0.004). Patients with at least 2 EDs receiving >/=100% PD to any % V of circumference had AE compared to those with zero EDs. CONCLUSIONS: Reirradiation using hypofractionated three-dimensional radiotherapy and SBF immobilization is an effective strategy for palliation of symptoms in selected patients with recurrent NSCLC. The length of the esophagus in the RT field does not predict for AE. However, an increasing number of EDs displaying the combination of longitudinal and circumferential three-dimensional dose distribution along the esophagus is a valuable predictor for AE.     

Dosimetric correlates for acute esophagitis in patients treated with radiotherapy for lung carcinoma

PURPOSE: Acute esophagitis is a common complication of radiotherapy (RT) for non-small-cell carcinoma of the lung. Previous reports have related esophagitis to dosimetric parameters such as the length of the irradiated esophagus, maximal dose, or volume of the organ treated beyond a threshold dose. However, when using oblique beams, a portion of the esophageal circumference may be outside the treated field, resulting in partial esophageal irradiation. Therefore, our aim was to determine whether the irradiated esophageal surface area and/or esophageal volume are predictive of acute esophagitis in relation to other clinical and treatment-related factors. METHODS AND MATERIALS: Complete dose-volume information was gathered for 166 patients receiving definitive RT for Stage I-IIIB non-small-cell carcinoma of the lung at our institution. Seventy-eight patients received chemotherapy (37 before RT and 41 concurrently). All patients were treated to doses of 60-74 Gy (median, 70 Gy) delivered in single daily fractions of 1.8-2.1 Gy. The doses were prescribed to the isocenter without using heterogeneity corrections; however, the doses were corrected to account for lung heterogeneity in this report. Esophageal contrast was used to contour the esophagus from the cricoid to the gastroesophageal junction in each case. Esophagitis was scored according to the Radiation Therapy Oncology Group criteria with Grade 2 or worse considered clinically significant. To determine the importance of the irradiated surface area, the volumetric treatment plan for each patient was prepared for analysis by relating a surface area to each point of the esophagus contour. Spearman's rank correlation was used to correlate the esophagitis score with A(d), where A represents the surface area (in centimeters squared) receiving the dose, d, or greater (in Gray), or V(d), where V represents the volume (in centimeters cubed) receiving d (in Gray). The surface areas studied were A(5)-A(80) or V(5)-V(80) in 5-Gy increments. The clinical parameters studied in univariate analysis included patient age, stage, performance status, use of pretreatment chemotherapy, and use of concurrent chemotherapy. Step-wise regression analysis was then used to determine the statistically significant factors predicting acute esophagitis. RESULTS: Forty-five patients (27%) developed Grade 2 or worse esophagitis, 37 developed Grade 2, 7 Grade 3, and 1 Grade 4. No deaths resulted from this complication. The most statistically significant single parameters for predicting acute esophagitis were A(55), V(60), and the use of concurrent chemotherapy. Age, stage, performance status, and pre-RT chemotherapy had no statistically significant influence on the incidence of acute esophagitis. On logistic regression analysis, A(55) (p < or =0.0005), V(60) (p < or =0.001), and the use of concurrent chemotherapy (p = 0.001) emerged as statistically significant correlates of acute esophagitis. CONCLUSION: The esophageal surface area receiving > or =55 Gy, the esophageal volume receiving > or =60 Gy, and the use of concurrent chemotherapy were the most statistically significant predictive factors for early esophagitis. Adequate dosimetric coverage of the planning target volume remains the goal of RT planning. High values of A(55) and/or V(60) are indicative of the development of acute esophagitis and may indicate a need to explore alternative RT planning options.     

Predictors of PEG dependence after IMRT ± chemotherapy for oropharyngeal cancer

Purpose

To prospectively assess predictors of PEG dependence after IMRT with/without concomitant chemotherapy (CHT).

Methods and materials

One-hundred-seventy-one patients were considered (exclusive RT: 58, RT+CHT: 113; 159/171 treated at a median dose of 70 Gy, 2 Gy/fr). Patients treated with RT+CHT underwent prophylactic PEG insertion; PEG was as needed for the others. A number of clinical factors and dose–volume information concerning oral mucosa (OM), constrictors, masticatory muscles, larynx, esophagus and parotids were available. The 25th/10th percentiles of the duration of PEG dependence were our end-points (respectively 3.3 and 7 months, PEG3/PEG7). Logistic uni and multi-variate (MVA) analyses were performed.

Results

Concerning PEG3, the independent predictors at MVA were: CHT/PEG policy (OR: 6.8, p = 0.001), V9.5G_OM Gy/week (OR: 1.017, p = 0.01), larynx V50 (OR: 1.018, p = 0.01) and superior constrictor (SC) D_mean (OR: 1.002, p = 0.005); the predictive value of the model (AUC) was 0.818 (95% CI: 0.751–0.873). The independent predictors of PEG7 were: larynx V50 (OR: 1.042, p = 0.0005) and SC D_mean (OR: 1.003, p = 0.02), symptoms at diagnosis (yes vs no, OR: 3.6, p = 0.08) and sex (male vs female, OR: 0.25, p = 0.07); AUC was 0.897 (95% CI: 0.841–0.939).

Conclusions

OM V9.5 Gy/week and CHT/PEG_policy modulate the risk of early PEG dependence. For longer PEG dependence, larynx V50 (or D_mean) and SC D_mean are highly predictive, suggesting that the fibrosis of constrictors and larynx is the main cause.     

Early Toxicity and Patient-Reported Cosmetic Outcomes in Patients Treated With Adjuvant Proton-Based Radiotherapy After Breast-Conserving Surgery

IntroductionTo evaluate the dosimetric data, early toxicity, and patient-reported cosmetic outcomes in breast cancer patients treated with adjuvant proton-based radiotherapy (RT) after breast-conserving surgery.Materials and MethodsWe performed a retrospective review of our institutional database to identify breast cancer patients treated with breast-conserving surgery followed by proton-based RT from 2015 to 2020. Patient-reported cosmetic outcomes were graded as excellent, good, fair, or poor. Early toxicity outcomes were graded by the treating physician during treatment. Dose-volume histograms were reviewed to obtain dosimetry data.ResultsWe identified 21 patients treated with adjuvant proton-based RT. Median whole breast dose delivered was 46.8 Gy (range, 40.0-50.4 Gy). Target volumes included the regional lymph nodes in 17 patients (81%). Seventeen patients (81%) received a lumpectomy boost. The median planning target volume V95 was 94% (range, 77%-100%), V100 71% (range, 60%-97%), V110 2% (range 0%-18%), and median max point dose was 115% (range, 105%-120%). The median ipsilateral breast V105 was 367.3 cc (range, 0-1172 cc) and V110 was 24.1 cc (range, 0-321.3 cc). Grade 2 and 3 dermatitis occurred in 62% and 14% of patients, respectively. Grade 2 and 3 pain was reported by 33% and 10% of patients, respectively. Median follow-up at the time of cosmetic evaluation was 27 months (range, 5-42 months). Four patients (21%) reported fair cosmetic outcome and 15 patients (79%) reported good or excellent cosmetic outcome. No poor cosmesis was reported.ConclusionAdjuvant proton-based radiotherapy after breast-conserving surgery is well tolerated with acceptable rates of acute toxicities and a high rate of good-to-excellent patient-reported cosmetic outcomes.     

Concurrent chemoradiotherapy with S-1 for T2N0 glottic carcinoma

Early glottic carcinoma has a good prognosis compared to other head and neck carcinomas, but we must aim for larynx preservation in the treatment. Regarding T1N0, larynx preservation rates are favorable even with radiotherapy alone. However for T2N0, the treatment strategies differ in each institution, and larynx preservation rates range from 72% to 85%, and are not high enough. We conducted a study to determine the efficacy of the concurrent chemoradiotherapy with S-1 for T2N0 glottic carcinoma. In this study, 12 patients with T2N0 glottic type laryngeal squamous cell carcinoma enrolled from the year 2004 to 2006, received one reduction dose of S-1 (80 or 100 mg/day) with concomitant irradiation with a total dose of 60-70 Gy (2.0 Gy/fr). The 2-week administration of S-1 followed by one-week rest was repeated during irradiation. In terms of adverse events of Grade 3 and above, Grade 3 mucositis and dermatitis were found in 2 patients each, but there was no cancellation nor interruption of S-1 or irradiation. All patients achieved pathological CR at the time of evaluation after the primary treatment, and no recurrences have been seen yet in any of the primary sites. Concurrent chemoradiotherapy with S-1 showed efficacy in T2N0 glottis carcinoma. Further investigation of this treatment with long-term follow up results is warranted.     

Acute toxicity in definitive versus postprostatectomy image-guided radiotherapy for prostate cancer

PURPOSE: To assess the incidence of acute gastrointestinal (GI) and genitourinary (GU) injury and the dose-volume response in patients with clinically localized prostate cancer treated with image-guided radiotherapy using helical tomotherapy. METHODS AND MATERIALS: Between November 2004 and March 2007, 146 consecutive patients with localized prostate cancer were treated with helical tomotherapy at the City of Hope Medical Center. Of the 146 patients, 70 had undergone prostatectomy. Acute GI and GU toxicities were evaluated using the Radiation Therapy Oncology Group/European Organization for Research and Cancer of Medical scoring system. Events were scored for patients developing Grade 2 or greater morbidity within 90 days after the end of radiotherapy (RT). The dosimetric parameters included the minimal dose received by the highest 10%, 20%, 50%, 80%, and 90% of the target volume, the mean rectal dose, minimal rectal dose, maximal rectal dose, and the volume receiving > or =45, > or =65, and > or =70 Gy. These variables, plus the status of radical prostatectomy, hormonal therapy, RT techniques, and medical conditions, were included in a multivariate logistic regression analysis. A goodness-of-fit evaluation was done using the Hosmer-Lemeshow statistic. RESULTS: A dose-response function for acute GI toxicity was elicited. The acute GI Grade 2 or greater toxicity was lower in the definitive RT group than in the postoperative RT group (25% vs. 41%, p <0.05). Acute GU Grade 2 or greater toxicity was comparable between the two groups. No grade 3 or greater complications were observed. No dosimetric variable was significant for GU toxicity. For acute GI toxicity, the significant dosimetric parameters were the minimal dose received by 10%, 20%, and 50% of the target volume and the mean rectal dose; the most predictive parameter was the minimal dose received by 10% of the target volume. The dose-modifying factor was 1.2 for radical prostatectomy. CONCLUSION: The results of our study have shown that acute rectal symptoms are dose-volume related. Postprostatectomy RT resulted in a greater incidence of acute GI toxicity than did definitive RT. For postoperative RT, it would be prudent to use different dose-volume limits.