Dosimetric predictors of xerostomia for head-and-neck cancer patients treated with the smart (simultaneous modulated accelerated radiation therapy) boost technique

PURPOSE: To evaluate the predictors of xerostomia in the treatment of head-and-neck cancers treated with intensity-modulated radiation therapy (IMRT), using the simultaneous modulated accelerated radiation therapy (SMART) boost technique. Dosimetric parameters of the parotid glands are correlated to subjective salivary gland function. MATERIALS AND METHODS: Between January 1996 and June 2000, 30 patients with at least 6 months follow-up were evaluated for subjective xerostomia after being treated definitively for head-and-neck cancer with the SMART boost technique. Threshold limits for the ipsilateral and contralateral parotid glands were 35 Gy and 25 Gy, respectively. Dosimetric parameters to the parotid glands were evaluated. The median follow-up time was 38.5 months (mean 39.9 months). The results of the dosimetric parameters and questionnaire were statistically correlated. RESULTS: Xerostomia was assessed with a 10-question subjective salivary gland function questionnaire. The salivary gland function questionnaire (questions 1, 2, 3, 4, 6, and 9) correlated significantly with the dosimetric parameters (mean and maximum doses and volume and percent above tolerance) of the parotid glands. These questions related to overall comfort, eating, and abnormal taste. Questions related to thirst, difficulty with speech or sleep, and the need to carry water daily did not correlate statistically with the dosimetric parameters of the parotid glands. CONCLUSIONS: Questions regarding overall comfort, eating, and abnormal taste correlated significantly with the dosimetric parameters of the parotid glands. Questions related to thirst, difficulty with speech or sleep, and the need to carry water daily did not correlate statistically with the dosimetric parameters of the parotid glands. Dosimetric sparing of the parotid glands improved subjective xerostomia. IMRT in the treatment of head-and-neck cancer can be exploited to preserve the parotid glands and decrease xerostomia. This is feasible even with an accelerated treatment regimen like the SMART boost. More patients need to be evaluated using IMRT to identify relevant dosimetric parameters.     

Evaluation of salivary gland function after treatment of head-and-neck tumors with intensity-modulated radiotherapy by quantitative pertechnetate scintigraphy

PURPOSE: To evaluate salivary gland function after inversely planned stereotactic intensity-modulated radiotherapy (IMRT) for tumors of the head-and-neck region using quantitative pertechnetate scintigraphy. METHODS AND MATERIALS: Since January 2000, 18 patients undergoing IMRT for cancer of the head and neck underwent pre- and posttherapeutic scintigraphy to examine salivary gland function. The mean dose to the primary planning target volume was 61.5 Gy (range 50.4-73.2), and the median follow-up was 23 months. In all cases, the parotid glands were directly adjacent to the planning target volume. The treatment planning goal was for at least one parotid gland to receive a mean dose of <26 Gy. Two quantitative parameters (change in maximal uptake and change in the relative excretion rate before and after IMRT) characterizing the change in salivary gland function after radiotherapy were determined. These parameters were compared with respect to the dose thresholds of 26 and 30 Gy for the mean dose. In addition, dose-response curves were calculated. RESULTS: Using IMRT, it was possible in 16 patients to reduce the dose for at least one parotid gland to < or =26 Gy. In 7 patients, protection of both parotid glands was possible. No recurrent disease adjacent to the protected parotid glands was observed. Using the Radiation Therapy Oncology Group/European Organization for the Research and Treatment of Cancer scoring system, only 3 patients had Grade 2 xerostomia. No greater toxicity was seen for the salivary glands. The change in the relative excretion rate was significantly greater, if the parotid glands received a mean dose of > or =26 Gy or > or =30 Gy. For the change in maximal uptake, a statistically significant difference was seen only for the parotid glands and a dose threshold of 30 Gy. For the end point of a reduction in the parotid excretion rate of >50% and 75%, the dose-response curves yielded a dose at 50% complication probability of 34.8 +/- 3.6 and 40.8 +/- 5.3 Gy, respectively. CONCLUSION: Using IMRT, it is possible to protect the parotid glands and reduce the incidence and severity of xerostomia in patients. Doses <26-30 Gy significantly preserve salivary gland function. The results support the hypothesis that application of IMRT does not lead to increased local failure rates.     

Can Dose Reduction to One Parotid Gland Prevent Xerostomia? — A Feasibility Study for Locally Advanced Head and Neck Cancer Patients Treated with Intensity-modulated Radiotherapy

AimsDryness of the mouth is one of the most distressing chronic toxicities of radiation therapy in head and neck cancers. In this study, parotid function was assessed in patients with locally advanced head and neck cancers undergoing intensity-modulated radiotherapy (IMRT) with or without chemotherapy. Parotid function was assessed with the help of a questionnaire and parotid scintigraphy, especially with regards to unilateral sparing of the parotid gland.Materials and methodsIn total, 19 patients were treated with compensator-based IMRT between February 2003 and March 2004. The dose to the clinical target volume ranged between 66 and 70 Gy in 30–35 fractions to 95% of the isodose volume. Ipsilateral high-risk neck nodes received an average dose of 60 Gy and the contralateral low-risk neck received a dose of 54–56 Gy. Eight of 19 patients also received concomitant chemotherapy.ResultsSubjective toxicity to the parotid glands was assessed with the help of a questionnaire at 0, 3 and 6 months and objective toxicity was assessed with parotid scintigraphy at 0 and 3 months. The mean dose to the ipsilateral parotid gland ranged from 19.5 to 52.8 Gy (mean 33.14 Gy) and the mean dose to the contralateral gland was 11.1–46.6 Gy (mean 26.85 Gy). At a median follow-up of 13 months, 9/19 patients had no symptoms of dryness of the mouth (grade I), 8/19 had mild dryness of the mouth (grade II) and only 2/19 had grade III xerostomia, although the parotid gland could only be spared on one side in most of the patients.ConclusionsMinimising the radiation dose to one of the parotid glands with the help of IMRT in patients with advanced head and neck cancers can prevent xerostomia in most patients and parotid scintigraphy is a useful method of documenting xerostomia.     

鼻咽癌调强放疗对腮腺功能的影响

目的 评价调强放疗对鼻咽癌患者腮腺功能的影响.方法 搜集2003年前2年内83例初治患者放疗前、放疗结束时、放疗后6个月和1、2、3、4、5年的口干变化情况的资料,通过分析其与腮腺受照剂量关系来评价调强放疗对腮腺功能影响.结果 共入组83例,其中Ⅰ期4例,Ⅱ期31例,Ⅲ期31例,ⅣA期17例;16例接受放化综合治疗.中位随访时间65个月,5年局部和区域控制率为96%和95%,总生存率为80%.放疗后7个时间段轻和中度口干发生率分别为42%、51%、71%、77%、58%、38%、26%和52%、53%、21%、8%、3%、2%、2%,无重度口干.双侧腮腺受照射平均剂量为34.34 Gy.放疗后6个月口干分级与腮腺平均受照剂量呈正相关,双侧腮腺50%体积受照剂量是放疗后6个月时口干分级的独立影响因素.当腮腺平均剂量≤33 Gy和D50≤29 Gy时,腮腺功能可得到较好地保护.结论 调强放疗在提高鼻咽癌局部和区域控制率的同时,降低了腮腺的受照剂量,减少了腮腺功能的损伤.     

Intensity-modulated radiation therapy for head and neck cancers with bilateral irradiation of the neck : preliminary results]

PURPOSE: To report preliminary results of a prospective study of intensity-modulated radiotherapy (IMRT) for head and neck squamous cell carcinoma (HNC) with bilateral irradiation of the neck. PATIENTS AND METHODS: At the Alexis Vautrin Cancer Center, 23 patients have been treated with IMRT for HNC since January 2002-August 2003. The first 10 patients with a minimum follow-up of 3 months were analyzed. All tumors were oropharyngeal. There were four females and six males, with a mean age of 50 years (range 39-66). Stages were I-II in eight and III-IV in two. CTV1 was microscopic disease and N0 neck (prescribed dose : 50 Gy) and CTV2 was macroscopic disease and the volume at risk (prescribed dose: 66-70 Gy). PTV were CTV + 5 mm. Patient's immobilization consisted of a five-point head neck shoulder thermoplastic mask. Set-up verifications were done by semi-automatically matching portal images and digitized reconstructed radiographs. IMRT used dynamic multileaf collimation. Five patients (group A) received 50 Gy IMRT (two post-operative and three with a brachytherapy boost with a mean dose: 27.5 Gy), and five patients (group B) received 66-70 Gy IMRT (four post-operative). Acute and late normal tissue effects were graded according to the RTOG-EORTC radiation morbidity scoring criteria. RESULTS: With a median follow-up of 7.4 months (range 3-18.5), no patient died or had loco-regional relapse. The displacements were <4 mm in 98% cases. CTV1 and 2 received 95% of the prescribed dose in 100% of the volume. On average the mean dose to the contralateral parotid was 25.5 Gy for group A vs. 31 Gy for group B (P = 0.09). Mean doses <26 Gy were obtained in three of five patients in group A vs. zero of five patients in group B (P = 0.04). Acute skin toxicities were grade 1 in five patients, grade 2 in four and grade 3 in one. Acute mucositis cases were grade 1 in three patients, grade 2 in five and localized grade 3 in two. At 3 months, 50% of the patients had a grade 0-1 late xerostomia. CONCLUSION: The 26 Gy dose limit constraint to the contralateral parotid was easier to satisfy when IMRT was prescribed at a maximum dose of 50 Gy. Acute toxicity is low. The displacements in the mask indicate that it is possible to define the PTV as CTV + 4 mm. This reduction should decrease the mean dose to the parotids. At 3 months, a 50% rate of grade 0-1 late xerostomia encourages the hope of a very low rate at 2 years.     

Level II lymph nodes and radiation-induced xerostomia

PURPOSE: To investigate the influence of the cranial border of electively irradiated Level II lymph nodes on xerostomia in patients with oropharyngeal cancer using three-dimensional conformal and intensity-modulated radiotherapy (3D-CRT and IMRT). METHODS AND MATERIALS: The target volumes and organs at risk were delineated on the planning CT scans of 12 patients. Two elective target volumes were delineated. The first had the transverse process of the C1 atlas and the second had the transverse process of the C2 axis as cranial border of the Level II lymph nodes. 3D-CRT and IMRT planning were performed for both elective volumes, resulting in two plans per patient and technique, called the C1 and C2 plans, respectively. Irradiation of the ipsilateral elective volume up to C1 and the contralateral up to C2 was also performed for IMRT. The normal tissue complication probability (NTCP) for xerostomia 1 year after RT was calculated using the parotid mean dose. RESULTS: The average mean dose +/- standard deviation (SD) to the contralateral parotid gland was reduced from 33 +/- 5 Gy for the IMRT C1 plans to 26 +/- 4 Gy for the IMRT C2 plans and from 51 +/- 6 Gy to 49 +/- 7 Gy for the 3D-CRT C1 and C2 plans, respectively. The associated NTCP +/- SD for xerostomia was 38% +/- 10% for IMRT C1 plans and 24% +/- 6% for IMRT up to C2 on the contralateral side, regardless of which cranial border was irradiated on the ipsilateral side. For the 3D-CRT C1 and C2 plans, an NTCP value of 74% +/- 12% and 71% +/- 15% was obtained, respectively. The NTCP for xerostomia of the ipsilateral parotid gland was 53% +/- 17% and 45% +/- 20% for the IMRT C1 and C2 plans and 89% +/- 11% and 87% +/- 12% for the 3D-CRT C1 and C2 plans, respectively. CONCLUSION: Lowering the cranial border of the Level II lymph nodes from C1 to C2, in the case of bilateral elective neck irradiation, could be considered on the contralateral side when the risk of metastasis on that side is very low. This is especially true when IMRT is used, because the relative reduction of NTCP for xerostomia 1 year after RT could be up to 68% compared with conventional conformal RT up to C1.     

Sparing the parotid glands and surgically transferred submandibular gland with helical tomotherapy in post-operative radiation of head and neck cancer: a planning study.

BACKGROUND AND PURPOSE: To evaluate the feasibility of sparing the parotid glands and surgically transferred submandibular gland (SMG) by intensity modulated radiotherapy (IMRT) in post-operative cases of head and neck cancer (HNC). MATERIALS AND METHODS: Ten patients (larynx-2, base of tongue-4, tonsil-3, and unknown primary-1; pathologic stages III-IV) who underwent SMG transfers on the side of N0 neck along with definitive surgery were selected for this study. IMRT planning was done retrospectively using helical tomotherapy approach. Planning objective was to deliver 60 Gy to PTV1 and 54 Gy to PTV2 while maintaining the mean dose to the total parotid volume (TPV) and SMG less than 26 Gy. RESULTS: The mean dose (+/-SD) to the TPV and SMG were 25+/-0.6 Gy and 23+/-1.9 Gy, respectively. The D(95) for PTV1 and PTV2 were 59.9+/-0.1 Gy and 54.9+/-0.3 Gy, respectively, satisfying our planning goal for PTV coverage. The D(99) for PTV1 and PTV2 were 58.2+/-0.7 Gy and 49.5+/-2.2 Gy, respectively, showing that sparing the salivary glands did not result in underdosing of the PTVs. CONCLUSIONS: By combining the gland transfer and IMRT, the mean dose to TPV and transferred SMG could be reduced to less than 26 Gy in post-operative patients of HNC.     

Geometric factors influencing dosimetric sparing of the parotid glands using IMRT

PURPOSE/OBJECTIVE: To determine the relationship between the parotid volume, parotid-planning target volume (PTV) overlap, and dosimetric sparing of the parotid with intensity-modulated radiation therapy (IMRT). METHODS AND MATERIALS: Parotid data were collected retrospectively for 51 patients treated with simultaneous boost IMRT. Unresectable patients received 54 or 59.4 Gy to subclinical disease, 70 Gy to gross disease. Patients treated postoperatively received 54, 60, and 66 Gy to low-risk, high-risk, and tumor bed regions. Volume and mean dose of each gland and gland segments outside of and overlapping the PTV were collected. Proximity of each gland to each PTV was recorded. RESULTS: Dosimetric sparing (mean dose 21% overlap (p = <0.0001). Among spared glands, the median mean dose in the overlap region was 55.0 Gy in glands with < or =21% overlap, but only 45.4 Gy when overlap >21%. Median mean dose was 25.9 Gy to glands overlapping PTV(54) or PTV(59) alone and 30.0 Gy to those abutting PTV(70) (p < 0.001). Although proximity to PTV(70) was associated with higher parotid dose, satisfactory sparing was achieved in 24 of 43 ipsilateral glands. CONCLUSIONS: Dosimetric sparing of the parotid is feasible when the parotid-PTV overlap is less than approximately 20%. With more overlap, sparing may result in low doses within the overlap region, possibly leading to inadequate PTV coverage. Gland proximity to the high-dose PTV is associated with higher mean dose but does not always preclude dosimetric sparing.     

Compensator-based intensity-modulated radiotherapy in head and neck cancer: our experience in achieving dosimetric parameters and their clinical correlation

AimsTo review the Batra Hospital and Medical Research Centre experience of using compensator-based intensity-modulated radiotherapy (IMRT) to treat head and neck cancer.Materials and methodsBetween October 2003 and August 2004, 18 patients underwent IMRT for head and neck cancer at our institution. IMRT was delivered using partial transmission high-resolution compensator blocks.ResultsWith a median follow-up of 13.3 months, two patients had residual disease and two failed in the gross tumour volume (GTV). The complete response rate after surgical salvage was 94.5%. Both the locoregional relapse-free and disease-free survival rates were 81.8%. The target coverage in terms of average maximum, mean and minimum dose (in Gy) delivered was 78.6, 73.5 and 58.4 to the GTV–planning target volume, 82.3, 70.9 and 47.3 to clinical target volume 1 (CTV1) and 82.9, 66.2 and 29.6 to CTV2. The dose constraint of 30 Gy to less than 50% of the contralateral parotid volume was achieved in 12 (66.7%) patients. If the dose constraint was revised to 35 Gy, at least 50% of the parotid volume was spared in 17 (94.5%) patients. On average, 75% of the contralateral parotid volume received a dose less than 35 Gy in 13 (72.3%) patients with grade I xerostomia, whereas this was 49.3% in five (27.7%) patients with grade II xerostomia, and the difference was statistically significant (P = 0.001).ConclusionsIn our initial experience, compensator-based IMRT is feasible with regard to target coverage and parotid volume sparing. The parotid volume dose has significant clinical implications on the grade of xerostomia. Our results invoke rethinking into the issues of the parotid volume dose constraint in our subpopulation.     

鼻咽癌调强放疗后近期腮腺功能影响因素分析

[目的]总结鼻咽癌调强放疗后腮腺功能影响因素。[方法]收集2008年7月至2009年8月初治的20例鼻咽癌调强放疗靶区及腮腺剂量学参数,随访其放疗后3个月口干情况,分析腮腺受照剂量与口干分级之间的关系。[结果]20例接受调强放疗鼻咽癌腮腺平均剂量41.25Gy,患侧腮腺V20：96.77%,V30：80.56%,V40：52.43%,健侧腮腺V20：971.47%,V30：69.95%,V40：40.85%。放疗后3个月轻度、中度、重度口干发生率分别为15%、55%、30%,口干分级与腮腺平均剂量、患侧及健侧腮腺V20、V30、V40呈正相关。[结论]鼻咽癌调强放疗后腮腺功能与腮腺受照体积、剂量显著相关。     

鼻咽癌调强放疗初步结果

目的:探讨鼻咽癌三维适形调强放射治疗(intensity-modulatedradiotherapy,IMRT)的初步疗效。方法:对91例经病理确诊的鼻咽低分化鳞癌患者进行调强放疗。处方剂量分别为GTV(鼻咽部和颈部淋巴结肿瘤靶区)66~70Gy,CTV1(临床靶区)60~62Gy,CTV2和CTVn(颈部淋巴结区域)54~56Gy。11例患者IMRT结束后有局部残留,1例采用IMRT追量照射10Gy/4次,其余给予鼻咽腔内后装追量照射9~15Gy/3~5次。分析疗效及放射治疗毒性。结果:中位随访时间12个月,1和2年生存率为97·1%和97·1%,局控率为97·1%和92·5%。急性放射反应多为Ⅰ度和Ⅱ度以口干和放射性口腔炎为主,分别占72·5%和58·2%。远期放射反应表现为不同程度的口干和听力下降,占患者的39·6%和17·6%。GTV、CTV1及CTV2的平均剂量分别为70·6、67·9和65·0Gy;5%体积的正常器官受照射剂量的平均值为:脑干41·4Gy,脊髓35·4Gy,左腮腺46·5Gy,右腮腺51·8Gy。结论:调强放疗能使得鼻咽癌各靶区得到很好的剂量分布,提高了初治鼻咽癌的局部控制率,明显减轻了急性放射反应。鼻咽癌IMRT处方剂量70Gy以上,CTV2预防照射的范围有待于进一步探讨。     

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.     

30例早期鼻咽癌调强放射治疗疗效分析

目的:探讨调强放射治疗(IMRT)对早期鼻咽癌的近期疗效和不良反应.方法:回顾分析30例早期鼻咽癌患者,鼻咽部和上颈部淋巴引流区采用IMRT技术照射,下颈部淋巴引流区采用颈前野常规照射.鼻咽大体肿瘤体积(GTVnx)处方剂量68Gy-74Gy,颈部淋巴结(GTVnd)处方剂量64Gy-70Gy,临床靶体积(CTV1)处方剂量 60Gy-64Gy,临床靶体积(CTV2)处方剂量 50Gy-54Gy,分30-34次进行照射.对于淋巴结分期为N1的患者,结合淋巴结的情况行诱导化疗和(或)同期化疗2-4周期,N0患者行单纯调强放射治疗.结果:鼻咽大体肿瘤体积(GTVnx)D95平均剂量为74.5Gy,GTVnx V95平均体积99.6%,脊髓D1cc平均剂量41.5Gy,脑干D3平均剂量50.3Gy,左腮腺D50平均剂量32.8Gy,右腮腺D50平均剂量31.4Gy,左颞叶D10平均剂量45.5Gy,右颞叶D10平均剂量45.2Gy,均低于限制剂量.中位随访时间33.5个月(4-45个月).1年、2年、3年的总生存率、无局部复发生存率和无远处转移生存率均为100%.最严重的急性反应是放射性黏膜炎,1-3级分别有 63.3%,30%,和6.7%,晚期不良反应主要表现为口干(Ⅰ度33.3%,Ⅱ度3.7%).结论:IMRT对初治早期鼻咽癌可获得理想的剂量分布,取得较好的近期疗效,正常组织得到很好的保护.     

鼻咽癌适形调强放疗中涎腺功能的全面保护

  目的  探讨鼻咽癌适形调强放疗(intensity modulate radiation therapy, IMRT)患者各涎腺功能的保护方法。  方法  选取2010年3月至2012年11月101例连续于中山大学肿瘤医院接受IMRT鼻咽癌患者, 勾画危及器官, 包括腮腺、颌下腺、口腔, 于3、6、12、18、24个月复查时采用面对面访谈式问卷调查评分口干程度情况, 并结合剂量体积直方图(dose-volume histograms, DVH)进行分析。  结果  腮腺平均剂量(MD)为37.4 Gy (患侧), 33.8 Gy (健侧); 颌下腺MD为51.6 Gy (患侧), 45.7 Gy (健侧); 口腔MD为38.2 Gy。77.2%(78/101)患者放疗结束后6个月口干症状明显改善, 1年后中度(G3)以上口干患者 < 5.0%(5/101)。  结论  随着时间的推移, 放疗后口干燥症明显改善; 限定至少一侧腮腺V30~35≤50.0%, 至少一侧颌下腺V40~45≤66.7%~50.0%, 口腔MD < 40 Gy可有效保护唾液腺功能。      

Intensity-modulated chemoradiation for treatment of stage III and IV oropharyngeal carcinoma: the University of California-San Francisco experience

BACKGROUND: Treatment outcomes for stage III and IV oropharyngeal carcinoma treated with intensity-modulated radiotherapy (IMRT) and concurrent chemotherapy without prior surgical resection were reviewed. METHODS: Between April 2000 and September 2004, 71 patients underwent IMRT concurrent with chemotherapy without prior surgical resection for stage III and IV oropharyngeal carcinoma. Chemotherapy was platinum based. The gross tumor volume (GTV) received 70 Gy in 2.12 Gy per fraction. The high-risk clinical tumor volume (CTV) received 59.4 Gy in 1.80 Gy per fraction, and the low-risk CTV received 54 Gy in 1.64 Gy per fraction. RESULTS: With a median follow-up of 33 months, the 3-year local, regional, and locoregional progression-free probabilities were 94%, 94%, and 90%, respectively. The 3-year overall survival estimate was 83%. Locoregional failures occurred in the GTV in 7 patients. Acute grade 3 or 4 toxicity developed in 35 patients. A feeding gastrostomy was placed in 25 patients. Late xerostomia was grade 0 in 16 patients, grade 1 in 31 patients, and grade 2 in 24 patients at last follow-up. No patients experienced grade 3 or 4 late toxicity, except for 1 who developed osteoradionecrosis of the mandible. CONCLUSIONS: Excellent local and regional control was achieved with IMRT and concurrent chemotherapy without prior surgical resection in the treatment of stage III and IV oropharyngeal carcinoma. Significant sparing of the parotid glands and other critical normal tissues was possible using IMRT with moderate acute toxicities and minimal severe late effects.     

Dynamic intensity-modulated non-coplanar arc radiotherapy (INCA) for head and neck cancer.

BACKGROUND AND PURPOSE: To define the potential advantages of intensity-modulated radiotherapy (IMRT) applied using a non-coplanar dynamic arc technique for the treatment of head and neck cancer. MATERIALS AND METHODS: External beam radiotherapy (EBRT) was planned in ten patients with head and neck cancer using coplanar IMRT and non-coplanar arc techniques, termed intensity modulated non-coplanar arc EBRT (INCA). Planning target volumes (PTV1) of first order covered the gross tumor volume and surrounding clinical target volume treated with 68-70 Gy, whereas PTV2 covered the elective lymph nodes with 54-55 Gy using a simultaneous internal boost. Treatment plan comparison between IMRT and INCA was carried out using dose-volume histogram and "equivalent uniform dose" (EUD). RESULTS: INCA resulted in better dose coverage and homogeneity of the PTV1, PTV2, and reduced dose delivered to most of the organs at risk (OAR). For the parotid glands, a reduction of the mean dose of 2.9 (+/- 2.0) Gy was observed (p = 0.002), the mean dose to the larynx was reduced by 6.9 (+/- 2.9) Gy (p = 0.003), the oral mucosa by 2.4 (+/- 1.1) Gy (p < 0.001), and the maximal dose to the spinal cord by 3.2 (+/- 1.7) Gy (p = 0.004). The mean dose to the brain was increased by 3.0 (+/- 1.4) Gy (p = 0.002) and the mean lung dose increased by 0.2 (+/- 0.4) Gy (p = 0.87). The EUD suggested better avoidance of the OAR, except for the lung, and better coverage and dose uniformity were achieved with INCA compared to IMRT. CONCLUSION: Dose delivery accuracy with IMRT using a non-coplanar dynamic arc beam geometry potentially improves treatment of head and neck cancer.     

Preservation of oral health-related quality of life and salivary flow rates after inverse-planned intensity- modulated radiotherapy (IMRT) for head-and-neck cancer

PURPOSE: To assess whether comprehensive bilateral neck intensity-modulated radiotherapy (IMRT) for head-and-neck cancer results in preserving of oral health-related quality of life and sparing of salivary flow in the first year after therapy. METHODS AND MATERIALS: Twenty-three patients with head-and-neck cancer (primary sites: nasopharynx [5], oral cavity [12], oropharynx [3], and all others [3]) were accrued to a Phase I-II trial. Inverse planning was carried out with the following treatment goals: at least 1 spared parotid gland (defined as the volume of parotid gland outside the planning target volume [PTV]) to receive a median dose of less than 20 Gy; spinal cord, maximum 45 Gy; PTV(1) to receive a median dose of 50 Gy; PTV(2) to receive a median dose of 60 Gy (postoperative setting, n = 15) or 66-70 Gy (definitive radiotherapy setting, n = 8). Treatment was delivered with 6 and 15 MV photons using a "step-and-shoot" technique on a Varian 2300 EX linac with 120-leaf Millenium MLC. Unstimulated and stimulated whole-mouth salivary flow rates were measured, and patients completed the University of Washington instrument (UWQOL) and a separate xerostomia questionnaire (XQOL) in follow-up. RESULTS: Early functional outcome end point data are available at the 1-, 3-, and 12-month follow-up time points for 22, 22, and 18 patients, respectively. The combined mean parotid dose was 30.0 Gy (95% confidence interval: 26.9-33.1). The differences from baseline in mean overall UWQOL scores at 1, 3, and 12 months postradiotherapy were -0.24, 0.32, and 4.28, not significantly different from zero (p = 0.89, p = 0.87, p = 0.13). None of the UWQOL individual domain scores related to oral health (pain, eating-chewing, eating-swallowing, and speech) at 1, 3, or 12 months were significantly different from baseline. Both unstimulated and stimulated whole-mouth flow was variably preserved. Unstimulated salivary flow at 1 and 12 months was inversely correlated with combined mean parotid dose (p = 0.014, p = 0.0007), whereas stimulated salivary flow rates at 3 and 12 months were also correlated with combined mean parotid dose (p = 0.025, p = 0.0016). Combined maximum parotid dose was correlated with unstimulated flow rate at 12 months (p = 0.02, r = -0.56) and stimulated flow rate at 1 and 12 months (p = 0.036, r = -0.45; p = 0.0042, r = -0.66). The proportion of patients reporting total XQOL scores of 0 or 1 (no or mild xerostomia) did not diminish significantly from baseline at 1, 3, or 12 months (p = 0.72, p = 0.51, p = 1.0). Unstimulated and stimulated flow at 1 month was inversely correlated with total XQOL score at 12 months (p = 0.025, p = 0.029). CONCLUSIONS: Oral health-related quality of life (HRQOL) was highly preserved in the initial 12 months after IMRT, as assessed with separate, validated instruments for xerostomia-specific quality of life and oral HRQOL. In general, patients with better-preserved unstimulated salivary flow rates tended to report lower xerostomia scores. Whole-mouth salivary flow rates post IMRT were inversely correlated with combined mean parotid doses. Longer follow-up is required to assess to what extent HRQOL is favorably maintained.     

Patterns of failure in patients receiving definitive and postoperative IMRT for head-and-neck cancer

PURPOSE: To analyze the patterns of locoregional failure in patients with head-and-neck cancer treated with inverse planning intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: Between February 1997 and December 2000, 165 patients with histologically confirmed head-and-neck cancer were treated using a parotid-sparing inverse planning IMRT protocol. Thirty-nine patients who received either palliative repeat irradiation or IMRT as a boost were excluded from this analysis, leaving 126 patients for this analysis. Of the 126 patients, 30 were women and 96 were men (median age 56 years, range 13-84). Fifty-two patients (41%) received definitive IMRT. Of the 52 patients, 17 were treated with RT alone and 35 with concurrent cisplatin-based chemotherapy regimens. Seventy-four patients (59%) received postoperative IMRT. The median follow-up was 26 months (range 12-55). IMRT was used only in the upper neck for salivary sparing. The lower neck was treated with a conventional AP low-neck port abutted to the inferior IMRT dose distribution border. The radiation dose was prescribed to the two clinical target volumes (CTVs) according to the assumed risk of containing disease. The mean dose for definitive IMRT patients was 72.64 +/- 4.83 Gy to CTV1 and 64.34 +/- 5.15 Gy to CTV2. The mean dose to CTV1 and CTV2 in postoperative cases was 68.53 +/- 4.71 Gy and 60.95 +/- 5.33 Gy, respectively. The locations of failure were analyzed. RESULTS: Seventeen locoregional failures (persistent or recurrent disease) were found. Of these 17 failures, 9 (53%) were inside CTV1. One failure (6%) was marginal to CTV1 but inside CTV2. One failure (6%) occurred outside CTV1 but inside CTV2. Another failure was marginal to CTV2. Of the 17 failures, 5 (28%) were found outside of the IMRT field and in the lower neck. Dose-volume histogram analysis revealed that for all but 1 patient, the recurrent/persistent disease within the CTVs received comparable or superior dose coverage relative to the CTV. The 2-year actuarial locoregional control rate was 85%, and the ultimate locoregional control rate after surgical salvage was 89%. We observed no dermal failure and only one marginal failure in the region adjacent to the spared parotid glands. CONCLUSION: We have shown that the target definition and coverage for patients treated with IMRT for parotid sparing is adequate. The predominant tumor failure within CTV1 may imply the need to identify patients with radioresistant tumor subvolumes (such as hypoxic regions) within the CTV. This information would assist in discriminating a subgroup of tumors for a more aggressive and target-specific therapeutic approach.