Reducing the Risk of Xerostomia and Mandibular Osteoradionecrosis: The Potential Benefits of Intensity Modulated Radiotherapy in Advanced Oral Cavity Carcinoma

Radiation therapy for squamous cell carcinoma of the oral cavity may be curative, but carries a risk of permanent damage to bone, salivary glands, and other soft tissues. We studied the potential of intensity modulated radiotherapy (IMRT) to improve target volume coverage, and normal tissue sparing for advanced oral cavity carcinoma (OCC). Six patients with advanced OCC requiring bilateral irradiation to the oral cavity and neck were studied. Standard 3D conformal radiotherapy (3DCRT) and inverse-planned IMRT dose distributions were compared by using dose-volume histograms. Doses to organs at risk, including spinal cord, parotid glands, and mandible, were assessed as surrogates of radiation toxicity. PTV1 mean dose was 60.8 ± 0.8 Gy for 3DCRT and 59.8 ± 0.1 Gy for IMRT (p = 0.04). PTV1 dose range was 24.7 ± 6 Gy for 3DCRT and 15.3 ± 4 Gy for IMRT (p = 0.001). PTV2 mean dose was 54.5 ± 0.8 Gy for 3DCRT and for IMRT was 54.2 ± 0.2 Gy (p = 0.34). PTV2 dose range was improved by IMRT (7.8 ± 3.2 Gy vs. 30.7 ± 12.8 Gy, p = 0.006). Homogeneity index (HI) values for PTV2 were closer to unity using IMRT (p = 0.0003). Mean parotid doses were 25.6 ± 2.7 Gy for IMRT and 42.0 ± 8.8 Gy with 3DCRT (p = 0.002). The parotid V30 in all IMRT plans was <45%. The mandible V50, V55, and V60 were significantly lower for the IMRT plans. Maximum spinal cord and brain stem doses were similar for the 2 techniques. IMRT provided superior target volume dose homogeneity and sparing of organs at risk. The magnitude of reductions in dose to the salivary glands and mandible are likely to translate into reduced incidence of xerostomia and osteoradionecrosis for patients with OCC.     

Application of hypoglossal nerve constraint in definitive radiotherapy for nasopharyngeal carcinoma: A dosimetric feasibility study

Purpose: Radiation-induced hypoglossal nerve palsy is an infrequent but debilitating late complication after definitive radiotherapy for head and neck cancers. D1cc < 74 Gy (equivalent dose in 2 Gy fractions, EQD2) has been proposed as a potential dose constraint that limits 8-year palsy risk to < 5%. This study sets to perform detailed dosimetric assessments on the applicability of this novel dose constraint in advanced nasopharyngeal carcinoma (NPC). Materials and methods: This is a retrospective single-institution dosimetry study. NPC radiotherapy plans were identified from an institutional database, with an aim to select 10 eligible cases. Bilateral hypoglossal nerves were retrospectively contoured following a standard atlas. Cases with either one, or both, hypoglossal nerves D1cc exceeded 74 Gy EQD2 were included. Dosimetry of hypoglossal nerves, planning target volumes (PTV) and normal structures before and after application of the new hypoglossal nerve constraint were compared and analyzed. Results: Ten NPC cases were replanned. All hypoglossal nerve contours overlapped with high-dose PTV, predominantly at regions of gross nodal diseases. D1cc in 15 out of 20 hypoglossal nerves exceeded 74G y EQD2 at initial plans. All nerves fulfilled the pre-specified constraint of 74Gy EQD2 after re-plan. Median hypoglossal nerve D1cc reduced from 74.8Gy (range, 74.1 to 77.4Gy) to 73.5Gy (range, 72.4 to 74.0Gy) (p < 0.001), corresponded to a projected reduction in 8-year palsy risk from 5%-14% to 3%-5%. PTV V100 was maintained above 95% in all cases. Dose increments in near-maximum (D2) and decrements in near-minimum (D98) were < 1 Gy. Safety dosimetric parameters of standard head and neck organs-at-risk showed no significant changes. Conclusions: Hypoglossal nerve D1cc < 74 Gy EQD2 is a dosimetrically feasible constraint in definitive radiotherapy for NPC. Tumor target coverage and normal organ dosimetry were not compromised with its usage. Its routine application should be considered in definitive radiotherapy for head and neck cancers.     

ConPas: a 3-D Conformal Parotid Gland-Sparing Irradiation Technique for Bilateral Neck Treatment as an Alternative to IMRT

BACKGROUND AND PURPOSE: Intensity-modulated radiotherapy (IMRT) is used in most reported techniques for bilateral neck irradiation that aim at parotid gland sparing. A relatively simple conformal parotid-sparing technique (ConPas) was developed that uses no beam-intensity modulation. The purpose of this paper is to demonstrate, in patients with larynx or hypopharynx carcinoma, that ConPas enables adequate coverage of the primary tumor and the bilateral neck nodes, while keeping the mean parotid dose (MPD) < 26 Gy. PATIENTS AND METHODS: Treatment plans using ConPas and the conventional technique (using one anteroposterior supraclavicular and two lateral beams) were computed for ten consecutive patients with T1-4 N0-1 larynx or hypopharynx carcinoma (not T1 glottic). A dose of 46 Gy was prescribed to the primary tumor and the bilateral neck nodes, planned either with the conventional technique or ConPas, followed by a boost up to 70 Gy with a simple two-field technique. The target coverage of both techniques was compared using the V(95), the percentage of the planning target volume (PTV) of the primary tumor and nodal regions receiving at least 95% of the prescribed elective dose. The MPDs and the normal-tissue complication probabilities (NTCPs) of the parotid glands were compared using either technique including the boost up to 70 Gy. Dosimetric verification of the technique has been carried out, using ionization chamber measurements and film dosimetry. RESULTS: The mean V(95) was 85.2% and 91.2% (p = 0.08), the mean MPD 38.7 Gy and 25.4 Gy (p < 0.001), and the mean NTCP for the parotid glands 0.87 and 0.22 (p < 0.001) for the conventional technique and ConPas, respectively. The dosimetric verification shows a good agreement between dose calculation and measurement. CONCLUSION: ConPas enables adequate target coverage and clinically relevant parotid sparing in bilateral neck irradiation without beam-intensity modulation.     

Dosimetric comparison of intensity-modulated radiation therapy for early-stage glottic cancers with and without the air cavity in the planning target volume

For early-stage glottic cancers, intensity-modulated radiation therapy (IMRT) has been shown to have comparable local control to 3D-conformal radiotherapy with the advantage of decreased dose to the carotid arteries. The planning target volume (PTV) for early glottic cancers typically includes the entire larynx, plus a 3 to 5 mm uniform margin. The air cavity within the larynx creates a challenge for the inverse optimization process as the software attempts to “build up” dose within the air. This unnecessary attempt at dose build-up in air can lead to hot spots within the rest of the PTV and surrounding soft tissue. We hypothesized that removal of the air from the PTV would decrease hot spots and allow for a more homogeneous plan while still maintaining adequate coverage of the PTV.We analyzed 20 consecutive patients with early-stage glottic cancer, T1-2N0, who received IMRT at our institution from April 2015 to December 2016. Each patient received 63 to 65.25 Gy in 2.25 Gy per fraction. Two plans were created for each case: one in which the PTV included the laryngeal air cavity and one in which the air cavity was subtracted from the PTV to create a new PTV-air structure. Dosimetric variables were collected for PTV-air structure from both IMRT plans, including V100%, D98% D2%, and D0.2%. Dosimetric variables for spinal cord and the carotid arteries were also recorded. Homogeneity index (HI) defined as D98/D2 was calculated. Two-sided t-tests were used to compare dosimetric variables.The median PTV volume was 69.9 cc (standard deviation [SD] ± 28.7 cc) and the median air cavity volume removed was 11.0 cc (SD ± 3.4 cc). A 2-sided t-test revealed a statistically significant decrease in max dose (112.7% vs 108.8%, p value = 0.0002) and improvement of HI (0.93 vs 0.91, p value = 0.0023) for the PTV air in the IMRT plan optimized for PTV air, which had air excluded, compared to the IMRT plan optimized for PTV with air included. There was no significant worsening of PTV-air coverage or significant increase in doses to the organs at risk (OARs).The removal of the air cavity from the PTV for early-stage glottic cancers does not compromise PTV coverage or sparing of OARs and can result in a more homogeneous IMRT plan. A more homogeneous plan has the potential to reduce treatment morbidity, although further study is warranted to investigate the clinical impact of air cavity removal from the PTV.     

Submandibular gland sparing when irradiating neck level IB in the treatment of oral squamous cell carcinoma

Patients with oral squamous cell carcinoma (OSqCCA) frequently require postoperative radiation (PORT), which may include contralateral level IB within the clinical target volume (CTV). The submandibular gland (SMG) is typically included within the level IB CTV; however, the SMG does not contain lymph nodes or lymphatic vessels. We hypothesized that level IB could be adequately irradiated while sparing the SMG to reduce xerostomia. Twelve patients with OSqCCA receiving PORT, which included the contralateral level IB within the planning target volume (PTV), were retrospectively reviewed and replanned using volumetric modulated arc therapy. CTV contouring, including contralateral level IB, was in accordance with the consensus contouring atlas but excluded the SMG. The contralateral neck PTVs were planned to 54 Gray (Gy) (PTV54). Dose requirements were per Radiation Therapy Oncology Group-1008: PTV54 D95% >54 Gy, with an allowable variation of >48.6 Gy. The dose constraint for the SMG was mean dose ≤39 Gy based on published dose-effect data for the SMGs. Mean SMG and PTV54 doses were 38.5 Gy and 56.3 Gy, respectively. Median PTV54 D95% was 53.0 Gy (range 52.5 to 54.6 Gy), with all cases meeting our allowable coverage goal. When assessing the portion of the PTV associated with level IB only (PTV_IB), mean PTV_IB dose was 54.4 Gy and median PTV_IB D95% was 43.3 Gy (range 42.5 to 52.2). Median D95% to CTV_IB was 50.2 Gy. SMG sparing resulted in 10% to 20% underdosing of the part of the PTV corresponding to level IB, as a portion of the PTV lies within the SMG. The SMG can be spared to a mean dose ≤39 Gy with slight underdosing of the surrounding PTV where the PTV overlaps with the SMG. Clinical trials evaluating SMG sparing are warranted.     

Etablierung einer 3D-Konformationstechnik zur Radio therapie von Kopf-Hals-Tumoren unter Berücksichtigung der Parotisschonung

PURPOSE: The aim of this study was to improve the irradiation technique for the treatment of head-and-neck tumors and, in particular, to make use of the advantages found in modern 3D planning to protect the parotid glands. PATIENTS AND METHODS: For this investigation the 3D dataset of a standard patient with oropharyngeal carcinoma of UICC stage IVA was used. In the CT scans (slice thickness 5 mm) the planning target volume (PTV), the boost volume and both parotids were delineated. Three different techniques were calculated for two different dose levels (50 Gy for PTV and 64 Gy for boost volume, using single doses of 2 Gy). For technique 1 (T1) a parallel opposed field photon/electron irradiation was designed, for technique 2 (T2) an opposed/arc field irradiation was employed, and for technique 3 (T3) a combination of a static coplanar and arc field irradiation was designed. The sum doses D(min), D(max) and D(mean) for PTV, boost volume, and ipsilateral and contralateral parotid gland were evaluated, and the time needed for calculation of the plans was also determined. RESULTS: For all techniques used, the calculated doses in the PTV (D(min) 5.6 +/- 0.1 Gy, D(max) 73.7 +/- 0.1 Gy, and D(mean) 57.9 +/- 0.5 Gy) and in the boost volume (D(min) 46.9 +/- 1.5 Gy, D(max) 73.8 +/- 0.12 Gy, and D(mean) 65.8 +/- 0.9 Gy) were equal. Significant differences were found regarding the three different techniques, e.g., for the ipsilateral parotid gland D(min) (T1 = 47.4, T2 = 50.6, and T3 = 38.4 Gy) as well as for the contralateral parotid gland D(min) (T1 = 42.1, T2 = 44.2, and T3 = 17.8 Gy) and D(mean) (T1 = 51.3, T2 = 52.8, and T3 = 32.6 Gy). Regarding the three different techniques, significant differences were found in favor of T3. The determined planning times were as follows: T1 = 90, T2 = 60, and T3 = 90 min. CONCLUSION: The combination of static coplanar and arc field technique (T3) resulted in a substantially better protection as compared to both other techniques. This was especially the case with regard to the contralateral parotid gland, when the dose distributions were calculated equally for PTV and boost volume. In this study, the D(mean) dose of the contralateral parotid gland was lower than the TD(50) of 37 Gy (95% confidence interval 32-43 Gy) previously assumed by the authors. Therefore, it can be concluded that in the present study a more intensive protection of this gland and a reduction in xerostomia were possibly obtained.     

Permanent breast seed implant for partial breast radiotherapy after partial mastectomy for favorable breast cancer: Technique,results, and applications to various seroma presentations

PurposeAdjuvant partial breast radiotherapy is the standard of care for early-stage favorable breast cancer. We report dosimetry, acute and late tolerance for 67 permanent breast seed implants.Materials and MethodsFrom July 2012 to October 2018, 67 postmenopausal women with unifocal pT1pN0 invasive ductal or ductal carcinoma in situ received partial breast radiotherapy using stranded Pd-103 seeds after breast-conserving surgery, delivering 90 Gy to the seroma + margin (1.25–1.5 cm), planned with computed tomography simulation and performed as an ultrasound-guided outpatient procedure. The planning and postimplant computed tomography images were fused for seroma delineation for postimplant dosimetry. Evaluations were performed at 1, 2, 6, and 12 months and then annually.ResultsAlthough patient acceptance is high, only 40% met technical requirements of seroma volume, location, and visibility. For 67 patients, the median seroma volume was 6.6 cc, PTV 61 cc, and number of needles 18. In day 0 dosimetry, median seroma D90 dose was 132 Gy; seroma + 5 mm, 106 Gy; and seroma + 10 mm, 80 Gy. Peak reaction at 6 weeks is limited to the implant site: 51% grade 1 erythema and 12% focal desquamation. Late reactions (>2 years) are generally minimal: 35% no sequelae, 43% localized fibrosis, 20% mild telangiectasia (6% moderate but asymptomatic), 22% contour change. At minimum 6-month follow-up, 94% were “very or totally satisfied.” Recurrences (median follow-up: 3.3 years) were one in breast (different quadrant) and 2 contralateral. Three patients have had biopsies of fibrosis, all negative for malignancy.ConclusionsOur experience with permanent breast seed implant is favorable with a high patient acceptance and satisfaction, excellent early efficacy, and very satisfactory cosmesis.     

Dosimetric study of optimal beam number and arrangement for treatment of nasopharyngeal carcinoma with intensity-modulated radiation therapy

The purpose of this dosimetric study was to evaluate the effect of beam number and arrangement on the dose distribution with intensity-modulated radiation therapy in patients with nasopharyngeal cancer. Computed tomography data sets of seven patients who were treated for nasopharyngeal carcinoma at the Peter MacCallum Cancer Centre were used for the present dosimetric study. The dose planned was 70 Gy in 7 weeks for the gross nasopharyngeal and nodal disease and the biological equivalents of 60 Gy in 6 weeks for the high-risk and 50 Gy in 5 weeks for the low-risk nodal disease. A plan using seven fields was compared to that using nine fields in all patients. Plans were assessed on the dose to the planning target volume (PTV) and the degree of parotid sparing achieved by evaluating both dose-volume histograms (DVH) and axial slices. Seven fields (three anterior and four posterior) provide good PTV coverage and satisfactory parotid sparing in patients with localized nasopharyngeal lesions. Nine fields appear to be better for tumours with significant posterolateral parapharyngeal extension. Parotid sparing is consistently better with nine fields. Both DVH and axial slices need to be evaluated before accepting any plan.     

A class solution for volumetric-modulated arc therapy planning in postprostatectomy radiotherapy

This study is aimed to test a postprostatectomy volumetric-modulated arc therapy (VMAT) planning class solution. The solution applies to both the progressive resolution optimizer algorithm version 2 (PRO 2) and the algorithm version 3 (PRO 3), addressing the effect of an upgraded algorithm. A total of 10 radical postprostatectomy patients received 68 Gy to 95% of the planning target volume (PTV), which was planned using VMAT. Each case followed a set of planning instructions; including contouring, field setup, and predetermined optimization parameters. Each case was run through both algorithms only once, with no user interaction. Results were averaged and compared against Radiation Therapy Oncology Group (RTOG) 0534 end points. In addition, the clinical target volume (CTV) D₁₀₀, PTV D₉₉, and PTV mean doses were recorded, along with conformity indices (CIs) (95% and 98%) and the homogeneity index. All cases satisfied PTV D₉₅ of 68 Gy and a maximum dose < 74.8 Gy. The average result for the PTV D₉₉ was 64.1 Gy for PRO 2 and 62.1 Gy for PRO 3. The average PTV mean dose for PRO 2 was 71.4 Gy and 71.5 Gy for PRO 3. The CTV D₁₀₀ average dose was 67.7 and 68.0 Gy for PRO 2 and PRO 3, respectively. The mean homogeneity index for both algorithms was 0.08. The average 95% CI was 1.17 for PRO 2 and 1.19 for PRO 3. For 98%, the average results were 1.08 and 1.12 for PRO 2 and PRO 3, respectively. All cases for each algorithm met the RTOG organs at risk dose constraints. A successful class solution has been established for prostate bed VMAT radiotherapy regardless of the algorithm used.     

Larynx-sparing techniques using intensity-modulated radiation therapy for oropharyngeal cancer

The purpose of the current study was to explore whether the laryngeal dose can be reduced by using 2 intensity-modulated radiation therapy (IMRT) techniques: whole-neck field IMRT technique (WF-IMRT) vs. junctioned IMRT (J-IMRT). The effect on planning target volumes (PTVs) coverage and laryngeal sparing was evaluated. WF-IMRT technique consisted of a single IMRT plan, including the primary tumor and the superior and inferior neck to the level of the clavicular heads. The larynx was defined as an organ at risk extending superiorly to cover the arytenoid cartilages and inferiorly to include the cricoid cartilage. The J-IMRT technique consisted of an IMRT plan for the primary tumor and the superior neck, matched to conventional antero-posterior opposing lower neck fields at the level of the thyroid notch. A central block was used for the anterior lower neck field at the level of the larynx to restrict the dose to the larynx. Ten oropharyngeal cancer cases were analyzed. Both the primary site and bilateral regional lymphatics were included in the radiotherapy targets. The averaged V95 for the PTV57.6 was 99.2% for the WF-IMRT technique compared with 97.4% (p = 0.02) for J-IMRT. The averaged V95 for the PTV64 was 99.9% for the WF-IMRT technique compared with 98.9% (p = 0.02) for J-IMRT and the averaged V95 for the PT70 was 100.0% for WF-IMRT technique compared with 99.5% (p = 0.04) for J-IMRT. The averaged mean laryngeal dose was 18 Gy with both techniques. The averaged mean doses within the matchline volumes were 69.3 Gy for WF-MRT and 66.2 Gy for J-IMRT (p = 0.03). The WF-IMRT technique appears to offer an optimal coverage of the target volumes and a mean dose to the larynx similar with J-IMRT and should be further evaluated in clinical trials.     

Esophageal Cancer

PURPOSE: To present the results of a prospective phase II study in esophageal carcinoma. PATIENTS AND METHODS: Patients received single doses of 1.8 Gy up to 27 Gy, then concomitant boost to a total of 50.4 Gy (PTV2 [planning target volume], single dose 1.8 Gy) and 64.8 Gy (PTV1, single dose 1.2 Gy in the morning and 1.8 Gy in the afternoon) concurrently with 800 mg/m(2)/d 5-fluorouracil and 20 mg/m(2)/d cisplatin (weeks 1 and 5). High-dose-rate brachytherapy (2-3 x 6 Gy) on Fridays of weeks 4-6 used a customized applicator facilitating central placement and circumferential dose homogeneity. RESULTS: 50 patients with squamous cell carcinoma (90%) or adenocarcinoma and mostly advanced tumor stage were treated (82% T3/T4 and 70% N1). Median overall survival (median OS 16 months; 1-year-OS 61%; 2-year OS 29%) was significantly longer for patients without nodal disease (35 vs. 11 months; p = 0.01). Hematotoxicity was grade 3 in 11/50, and grade 4 in 1/50 patients. Four percent of higher-grade nausea or vomiting occurred. Esophageal late toxicity was grade 3 in 9/50 patients, and grade 4 in 2/50 patients. CONCLUSION: Survival was excellent especially for patients without nodal disease in this dose-intensified schedule with acceptable tolerability.     

Intraindividual Comparison of Conventional Three-Dimensional Radiotherapy and Intensity Modulated Radiotherapy in the Therapy of Locally Advanced Non-Small Cell Lung Cancer

BACKGROUND: Local failure is the one of the most frequent cause of tumor related death in locally advanced non-small cell lung cancer (LAD-NSCLC). Dose escalation has the promise of increased loco-regional tumor control but is limited by the tolerances of critical organs. PATIENTS AND METHODS: To evaluate the potential of IMRT in comparison to conventional three-dimensional conformal planning (3DCRT) dose constraints were defined: Maximum dose (D(max)) to spinal cord < 48 Gy, mean lung dose 70 Gy in not more than 5 cm of the total length. For ten patients two plans were compared: (1) 3DCRT with 5 weekly fractions (SD) of 2 Gy to a total dose (TD) of 50 Gy to the planning target volume of second order (PTV2). If the tolerance of the critical organs was not exceeded, patients get a boost plan with a higher TD to the PTV1. (2) IMRT: concomitant boost with 5 weekly SD of 2 Gy (PTV1) and 1.5 Gy to a partial (p)PTV (pPTV=PTV2 profile of a line PTV1) to a TD of 51 Gy to the pPTV and 68 Gy to the PTV1. If possible, patients get a boost plan to the PTV1 with 5 weekly SD of 2 Gy to the highest possibly TD. RESULTS: Using 3DCRT, 3/10 patients could not be treated with TD > 50 Gy, but 9/10 patients get higher TD by IMRT. TD to the PTV1 could be escalated by 16% on average. The use of non-coplanar fields in IMRT lead to a reduction of the irradiated lung volume. There is a strong correlation between physical and biological mean lung doses. CONCLUSION: IMRT gives the possibility of further dose escalation without an increasing mean lung dose especially in patients with large tumors.