Lymph node‐positive head and neck cancer treated with definitive radiotherapy

BACKGROUND: The purpose was to determine if postradiotherapy (RT) neck dissection can be limited to the neck levels of residual adenopathy on post-RT computed tomography (CT). METHODS: In all, 274 patients with lymph node-positive head and neck squamous cell carcinoma were treated with definitive RT. All patients had a contrast-enhanced CT performed 4 weeks after completing RT to evaluate tumor response. Two hundred eleven heminecks were dissected, either planned pre-RT or because of residual adenopathy on post-RT CT. CT images were reviewed to determine the presence and location of residual adenopathy. Radiographic complete response (rCR) was defined as lymph node size < or =1.5 cm and normal radiographic morphology (no filling defects or calcifications). For each neck level the CT findings were correlated with neck dissection pathology. RESULTS: Correlation of CT nodal response with neck dissection pathology revealed the following negative predictive values of rCR: level I, 100%; level II, 95%; level III, 98%; level IV, 96%; and level V, 96%. A subset analysis was performed on 61 neck levels with initially positive lymph nodes that completely responded to RT that were in a hemineck with residual lymphadenopathy elsewhere in the neck. Correlation of nodal response on CT to pathology indicated a negative predictive value of an rCR of 95% for this high-risk scenario. In 71 heminecks that underwent a selective neck dissection (defined as dissection of less than levels I-V) the 5-year neck control rate was 100%. CONCLUSIONS: rCR on post-RT CT has a negative predictive value of > or =95% for each neck level. This suggests that limiting neck dissection based on post-RT CT is safe.     

Intensity‐modulated radiotherapy: Examples of its utility in head and neck cancer

Intensity‐modulated radiotherapy (IMRT) has been available at Peter MaCallum Cancer Centre (PMCC) since November 2000. The present report illustrates two cases of our early experience with IMRT. Case 1 is a 66‐year‐old man with a T₁N₂M₀ nasopharyngeal carcinoma treated with chemo‐radiotherapy using parotid‐sparing IMRT. Fourteen months following treatment he remains in complete remission, with salivary function assessed using a xerostomia‐specific quality of life questionnaire, having returned to near pretreatment levels by 12 months. Case 2 is a 70‐year‐old man with a T₄N₀M₀ base of tongue squamous cell carcinoma treated with chemo‐radiotherapy after refusing radical surgery. He had received subtotal nodal irradiation to 36 Gy in 1994 for Hodgkins disease stage IIA. A radical dose was still achievable despite previous irradiation without exceeding unacceptable spinal cord dose with IMRT. He remains in complete remission 14 months from his initial presentation without evidence of neurological toxicity. Intensity‐modulated radiotherapy allows sparing of critical normal structures in the head and neck without compromising dose to the tumour. It is, therefore, desirable for several clinical applications and essential in some, if unacceptable compromises are not to be made.     

A comparison of several modulated radiotherapy techniques for head and neck cancer and dosimetric validation of VMAT

Purpose

Volumetric modulated arc therapy (VMAT) has the potential to shorten treatment times for fluence modulated radiotherapy. We compared dose distributions of VMAT, step-and-shoot IMRT and serial tomotherapy for typical head and neck (H&N) planning target volumes (PTV) with sparing of one parotid, a complex paradigm and a situation often encountered in H&N radiotherapy. Finally, we validated the dosimetric accuracy of VMAT delivery.

Material and methods

Based on CT datasets of 10 patients treated for H&N cancer (PTV1:60 Gy/PTV2:56 Gy) with IMRT (7/9 fields), serial tomotherapy (MIMiC) and VMAT were compared with regard to plan quality and treatment efficiency. Plan quality was assessed by calculating homogeneity/conformity index (HI/CI), mean dose to parotid and brain stem and the maximum dose to the spinal cord. For plan efficiency evaluation, total treatment time (TTT) and number of monitor units (MU) were considered. A dosimetric evaluation of VMAT was performed using radiosensitive film, ion chamber and 2D-array.

Results

For MIMiC/IMRT_7F/IMRT_9F/VMAT, mean CI was 1.98/2.23/2.23/1.82, HI_PTV1 was 1.12/1.20/1.20/1.11 and HI_PTV2 was 1.11/1.15/1.13/1.12. Mean doses to the shielded parotid were 19.5 Gy/14.1 Gy/13.9 Gy/14.9 Gy and the spinal cord received maximum doses of 43.6 Gy/40.8 Gy/41.6 Gy/42.6 Gy. The mean MU’s were 2551/945/925/521 and the mean TTT was 12.8 min/7.6 min/8.5 min/4.32 min. The ion chamber measurements showed an absolute deviation of 0.08 ± 1.10% and 98.45 ± 3.25% pixels passed γ-analyses for 3%/3 mm and 99.95 ± 0.09% for 5%/5 mm for films. 2D-array measurements reported an agreement for 3%/3 mm of 95.65 ± 2.47%-98.33 ± 0.65% and for 5%/5 mm 99.79 ± 0.24%-99.92 ± 0.09% depending on the measurement protocol.

Conclusion

All treatment paradigms produced plans of excellent quality and dosimetric accuracy with IMRT providing best OAR sparing and VMAT being the most efficient treatment option in our comparison of treatment plans with high complexity.     

头颈部肿瘤颈部放疗对甲状腺功能影响的研究进展

头颈部肿瘤颈部放疗后,会引起甲状腺功能减退（hypothyroidism,HT）,5年发生率于20%～60%之间。本文综述了放疗剂量-体积参数、年龄、放射技术、性别等因素与放射治疗引起的甲状腺功能减退（radiation-induced hypothyroidism,RIHT）的关系,以及产生的机制。甲状腺的剂量-体积阈值相关研究很多,但结论不一,不能明确定义。但共识是较高的甲状腺剂量和较小的甲状腺体积会增加RIHT的发生率,年龄、放射技术、性别会对RIHT的发生有影响。需大量前瞻性大样本进一步研究来开发更多的正常组织并发症概率 （normal tissue complication probability,NTCP）模型及探讨下丘脑-垂体轴和RIHT之间的关系。     

The dosimetric consequences of anatomic changes in head and neck radiotherapy patients

Introduction: To investigate anatomical response-related changes in the head and neck region during a course of radical radiotherapy and their impact on the planned dosimetry. Methods: The study consisted of 10 patients with primary mucosal carcinoma. Patients' nutritional requirements were managed as per departmental protocol to minimise weight loss during treatment. Kilovoltage computed tomography (CT) scans were acquired once 40 to 50 Gy had been delivered. Gross tumour volumes (GTV) and organs at risk were delineated and the initial optimised treatment plan was overlaid on the repeat CT. Comparisons were made between scans and absolute volume variations, centres of structures, dice similarity coefficients and the subsequent dosimetric impact were assessed. Results: Median weight loss at second scan was 3%. Primary and lymph node GTVs reduced by 49.9% (range 21.3–82%) and 73.7% (range 61.7–88.6%), respectively, yet continued to receive the prescribed dose. Maximum dose to spinal cord and brainstem changed minimally. Spared and un-spared parotid gland volumes reduced by median 23.5% and 20.5%, respectively, with no consistent translational displacement direction and minimal change in the mean dose. Conclusions: Despite some significant geometric changes, nutritional management ensured patient size and shape was maintained in these consecutively selected patients and subsequently there was no apparent under-dosing of targets or over-dosing of normal structures with this technique. Further investigations which model gradual change and allow cumulative dosimetry are required to better characterise what occurs during the treatment course.     

The effect of an intensive nutritional program on daily set‐up variations and radiotherapy planning margins of head and neck cancer patients

This is a prospective case‐control study to assess nutritional supplementation in limiting weight loss and its impact on daily set‐up variations and planning target volume (PTV) margins in head and neck (H&N) radiotherapy (RT). Twenty sequential H&N patients were recruited for this study. Ten patients had a percutaneous endoscopic gastrostomy (PEG) tube inserted prior to RT and 10 did not. PEG use was determined by departmental guidelines for patients considered at high risk for weight loss. Daily 2D electronic portal images were taken for orthogonal verification. Set‐up variations were determined for both PEG and non‐PEG patients by calculating systematic (Σ) and random (σ) errors, and PTV margins were derived. PEG patients lost less weight (P = 0.04) over the course of RT and had a reduction in set‐up variation in the superior–inferior (SI) and anterior–posterior (AP) planes compared to those without. Mean correctional shifts in mm (range) for PEG patients were: Right–Left (RL) 0.1 (?1.9–2.1), SI ?1.7 (?2.9–0.0), AP ?0.4 (?2.0–0.8), and for non‐PEG patients were: RL ?0.2 (?2.7–1.3), SI ?1.3 (?3.1–1.0), AP 0.4 (?1.5–2.8). The adapted PTV margins (mm) in the RL, SI and AP planes, respectively, for PEG patients were 4.1, 3.3 and 3.6, and for non‐PEG were 3.9, 4.9 and 4.8. Intensive enteral support maintained weight stability in H&N patients considered at risk of weight loss during RT and this was associated with reduced set‐up variation.     

Evaluation of trends in the use of intensity‐modulated radiotherapy for head and neck cancer from 2000 through 2005

BACKGROUND:

The current study was conducted to evaluate trends in utilization of intensity‐modulated radiotherapy (IMRT) for head and neck cancer (HNC).

METHODS:

Identified were 5487 patients from the Surveillance, Epidemiology, and End Results (SEER) ‐Medicare linked database with a diagnosis of HNC (aged ≥65 years) between 2000 and 2005, who received any type of radiotherapy (RT). Multivariate logistic regression analyses were performed to assess the influence of patient, tumor, treatment, and sociodemographic characteristics on receipt of IMRT versus conventional radiotherapy techniques.

RESULTS:

Overall, 21.3% of patients in the cohort received IMRT as the technique of irradiation. The use of IMRT increased significantly, with 1.3% of patients receiving it in 2000 compared with 46.1% in 2005 (P <.0001 for trend). Patients treated with RT in 2005 were 68 times more likely to receive IMRT than those treated in 2000. There was significant geographic variation observed in use of IMRT, ranging from 11.3% of cases in Kentucky to 40.4% of cases in Hawaii. Patients in the census tracks comprising the lowest quartile for socioeconomic status were 33% less likely to receive IMRT than patients in the highest quartile, even when adjusting for geographic area and year of diagnosis.

CONCLUSIONS:

The use of IMRT has rapidly become widespread for the delivery of RT for patients with HNC. However, there was significant geographic variation noted in the utilization of IMRT. Patients in census tracks comprising the lowest socioeconomic quartile were less likely to receive IMRT than their more affluent counterparts. Cancer 2010. © 2010 American Cancer Society.     

Efficacy and toxicity of reirradiation using intensity‐modulated radiotherapy for recurrent or second primary head and neck cancer

BACKGROUND:

Patients with locally recurrent squamous cell cancer of the head and neck (SCCHN) are reported to have a poor prognosis and limited therapeutic options. Optimal management is selectively applied and morbid. Both surgical resection and chemoradiotherapy are reported to result in median survivals of approximately 12 months. Intensity‐modulated radiotherapy (IMRT) is a highly conformal approach for delivering RT. This study reported the experience of the Dana‐Farber Cancer Institute (DFCI) with IMRT‐based chemoradiotherapy with or without surgery for locally recurrent SCCHN.

METHODS:

The current study was a retrospective study of all patients treated at DFCI who were diagnosed with nonmetastatic second primary or recurrent SCCHN and who received reirradiation based on IMRT. The primary endpoint was overall survival (OS), and secondary endpoints were locoregional (LRC) and distant control and acute and chronic toxicity.

RESULTS:

Thirty‐five patients were treated from August 2004 until December 2008. Recurrent disease was treated in the oral cavity (4 patients), larynx/hypopharynx (13 patients), oropharynx (7 patients), nasopharynx (2 patients), and neck (9 patients). The median radiation dose was 60 Gray (Gy), and all patients received concurrent chemotherapy. The median follow‐up was 2.3 years. The 2‐year actuarial OS and LRC rates were 48% and 67%, respectively. Approximately 91% and 46%, respectively, of all patients developed at least 1 acute and late grade 3 toxicity. Four (11%) late deaths occurred in patients with no evidence of disease (2 aspiration events, 1 oropharyngeal hemorrhage, and 1 infectious death).

CONCLUSIONS:

Aggressive chemoradiotherapy with IMRT was found to be feasible and resulted in favorable survival outcomes in comparison with published reports. Acute and late toxicities were substantial. The apparently improved LRC appears to carry a significant risk of developing late complications. Cancer 2010. © 2010 American Cancer Society.     

头颈部肿瘤放疗致听力损伤的研究进展

放射性听力损伤是头颈部肿瘤一种常见治疗相关并发症,耳蜗所受照摄剂量、随访时间为放射性听力损伤发病率的主要影响因素.改进放疗技术、限定听觉器官放疗剂量、积极治疗放射性中耳炎是防治放射性听力损伤的主要方法,人工耳蜗移植适用于听力完全丧失且无法恢复的患者.     

Combined concomitant boost radiotherapy and chemotherapy in stage III-IV head and neck carcinomas: A comparison of toxicity and treatment results with those observed after radiotherapy alone

Background: Alteration of radiation therapy (RT) fractionation and thecombination of chemotherapy (CT) with RT represent two predominant fields ofcurrent research in the treatment of head and neck carcinomas. To assess thepotential integration of these two fields, a retrospective comparison oftoxicity and treatment outcome was carried out in stage III–IV patientstreated with a concomitant boost RT schedule with or without CT.Patients and methods: Fifty-two patients were treated by RT alone and 35by RT and CT. In the RT group, there were significantly fewer T3–4tumors(56% vs. 88%, P = 0.002) and higher proportion of planned neckdissections (35% vs. 14%, P = 0.047). The planned total dose was69.9 Gy delivered over 5.5 weeks. In 10 cases CT was given before RT and in25 concomitantly with RT, either alone or with neoadjuvant and/or adjuvant CT.All patients but two had cisplatin-based (CDDP, 100mg/m²) CT, associated in 28 patients with 5-fluorouracil(5-FU, 1000 mg/m²/24 h × 5). The median follow-upfor the surviving patients was 21 and 31 months for the RT and RT–CTgroupsrespectively.Results: Grade 3–4 acute toxicity (RTOG) was observed in 73%and86% of patients, and grade 3 dysphagia in 31% and 57% (P=0.02) respectively in the RT and RT–CT groups. The rates of grade3–4 late complications were similar in the two groups (5% vs.12%). At three years, actuarial loco-regional control (LRC) was57% and 66% (P = 0.66) and overall survival was 56% and47% (P = 0.99) in the RT and RT–CT groups respectively.Conclusions: While acute toxicity was higher compared with RT alone, thisaccelerated RT schedule was feasible in association with 5-FU/CDDP, evenadministered concomitantly. Despite the significant proportion of moreadvanced disease in the RT–CT group, LRC was similar to that obtainedby RTalone. Combinations of concomitant boost RT and chemotherapy merit furtherinvestigation in prospective trials.     

Prospective observational study of carbon‐ion radiotherapy for non‐squamous cell carcinoma of the head and neck

To evaluate the efficacy and safety of carbon‐ion radiotherapy for non‐squamous cell carcinoma of the head and neck, 35 patients were enrolled in this prospective study. The primary end‐point was the 3‐year local control rate, and the secondary end‐points included the 3‐year overall survival rate and adverse events. Acute and late adverse events were evaluated according to the Common Terminology Criteria for Adverse Events, version 4.0. The median follow‐up time for all patients was 39 months. Thirty‐two and three patients received 64.0 Gy (relative biological effectiveness) and 57.6 Gy (relative biological effectiveness) in 16 fractions, respectively. Adenoid cystic carcinoma was dominant (60%). Four patients had local recurrence and five patients died. The 3‐year local control and overall survival rates were 93% and 88%, respectively. Acute grade 2–3 radiation mucositis (65%) and dermatitis (31%) was common, which improved immediately with conservative therapy. Late mucositis of grade 2, grade 3, and grade 4 were observed in 11, one, and no patients, respectively. There were no adverse events of grade 5. Carbon‐ion radiotherapy achieved excellent local control and overall survival rates for non‐squamous cell carcinoma. However, the late mucosal adverse events were not rare, and meticulous treatment planning is required. Trial registration no. UMIN000007886.     

Hypothalamic,pituitary and thyroid dysfunction after radiotherapy to the head and neck

One hundred-ten patients who had nasopharyngeal cancer and paranasal sinus tumors and were free of the primary disease were studied one to 26 years following radiotherapy. There were 70 males and 40 females ranging in age from 4 to 75 years, with a mean age of 36.5 years. During therapy both the hypothalamus and the anterior pituitary gland were in the field of irradiation. The radiation dose to the hypothalamus and the anterior pituitary gland was estimated to be 400 to 7500 rad with a median dose of 5618 rad to the anterior pituitary gland and a median dose of 5000 rad to the hypothalamus. We found evidence of endocrine deficiencies in 91 of the 110 patients studied. Seventy-six patients showed evidence of one or more hypothalamic lesions and 43 patients showed evidence of primary pituitary deficiency. Forty of the 66 patients who received radiotherapy to the neck for treatment or prevention of lymph node metastasis showed evidence of primary hypothyroidism. The range of the dose to the thyroid area was 3000 to 8800 rad with a median of 5000 rad. One young adult woman who developed galactorrhea and amenorrhea 2 years following radiotherapy showed a high serum prolactin level, but had normal anterior pituitary function and sella turcica. She regained her menses and had a normal pregnancy and delivery following bromocriptine therapy. These results indicate that endocrine deficiencies after radiotherapy for tumors of the head and neck are common and should be detected early and treated. Long-term follow-up of these patients is indicated since complications may appear after the completion of radiotherapy.     

Induction chemotherapy in head and neck cancer patients followed by concomitant docetaxel‐based radiochemotherapy

MENCOBONI M., GRILLO‐RUGGIERI F., SALAMI A., SCASSO F., REBELLA L., GRIMALDI A., DELLEPIANE M., MORATTI G., BRUZZONE A., SPIGNO F., GHIO R. & FIGLIOMENI M. (2010) European Journal of Cancer Care
Induction chemotherapy in head and neck cancer patients followed by concomitant docetaxel‐based radiochemotherapy Concurrent chemoradiotherapy has become the standard of care for patients with inoperable squamous cell head and neck carcinoma. More recently, induction chemotherapy has been adopted as an approach in the management of these patients. We report the results of a phase II trial associating induction chemotherapy and concomitant chemoradiotherapy in a series of patients with inoperable squamous cell head and neck cancer. Twenty‐nine patients with advanced squamous cell carcinoma ineligible for surgery were enrolled. Induction chemotherapy with docetaxel 75 mg/m² and cisplatin 75 mg/m² every 21 days was administered for two cycles. Radiotherapy followed the induction phase. During radiotherapy, docetaxel was administered weekly at the dose of 33 mg/m². Primary end point of the study was feasibility of treatment. Six (18%) patients failed to conclude the treatment schedule. Although response rates in evaluable patients were very high (disease control rate >90%), toxicities were a matter of concern. The reported treatment schedule proved infeasible. However, some modifications in ancillary therapies aimed at exploiting its efficacy could make it practicable.     

头颈部放疗对口腔菌群的影响

目的:探究头颈部放疗的肿瘤患者随着放疗剂量的累积口腔菌群的变化及不同程度的放疗相关性口腔黏膜炎、口腔菌群的变化.方法:选取2019年11月至2020年4月在某医院放疗科接受头颈部放射治疗的患者20名,放射剂量为6996 cGy,均行动态调强放射治疗.在患者放疗累积剂量为0～19 Gy、20～39 Gy、40 Gy时,采...     

头颈部肿瘤ART体积和剂量比较:系统评价与Meta分析

目的 对头颈部肿瘤放疗ART靶区与OAR体积和剂量变化系统评价与Meta分析,说明ART在治疗中作用。方法 文献检索纳入相关研究,分析指标原发肿瘤(GTV-T、GTV-N)与腮腺体积;靶区D₉₅ D_mean,同、异侧腮腺(I-PG、C-PG)D_mean,脊髓、脑干D_max。结果 17个研究336病例纳入Meta分析。原发肿瘤与腮腺体积变化明显,GTV-T、GTV-N、I-PG第15-20天及第20天后体积显著减小(P<0.05),C-PG第20天后显著减小(P=0.004)。实际剂量分析,原发肿瘤D_95、D_mean无变化,脊髓D_max第20-25天增加2.26 Gy (P=0.000),脑干D_max第20天前无显著变化(P=0.090),第25天后增加1.78 Gy (P=0.020),I-PG D_mean第20-25天增加2 Gy (P=0.000),C-PG D_mean第20天前增加,第25天后无显著变化(P=0.110)。ART剂量分析,脊髓、脑干D_max均下降(MD=-2.15,95% CI为-3.12~-1.18,P=0.000;MD=-2.20,95% CI为-3.32~-1.09,P=0.000),I-PG D_mean下降约3.5 Gy,敏感性分析显示C-PG D_mean结果不稳定。结论 原发肿瘤、腮腺体积显著变化,脊髓、脑干D_max,腮腺D_mean实际剂量显著增加,GTV-T、GTV-N剂量变化不明显,ART能很好保护OAR剂量要求,对同步放化疗局部晚期头颈部肿瘤患者第15-20天及第25天左右实施ART计划可能获得较好剂量增益。     

Concomitant weekly cisplatin and altered fractionation radiotherapy in locally advanced head and neck cancer

BACKGROUND:

Both concomitant chemotherapy and altered fractionation radiotherapy (RT) have been shown to improve outcomes for patients with locoregionally advanced head and neck squamous cell carcinomas. However, both strategies also increase acute toxicity, and it is questionable whether the 2 can be safely combined. Traditional concomitant chemotherapy regimens include high‐dose cisplatin given at 100 mg/m² every 3 weeks. The authors' purpose was to report efficacy and toxicity after weekly cisplatin (30 mg/m²/wk) concurrent with altered fractionation RT.

METHODS:

One hundred twenty‐one patients with American Joint Committee on Cancer stages II (3%), III (13%), or IV (84%) squamous cell carcinomas of the oropharynx (70%), hypopharynx (20%), or larynx (10%) were treated between 2000 and 2006 at the University of Florida with hyperfractionated RT (55 patients) or concomitant boost RT (66 patients) and concomitant cisplatin (30 mg/m²/wk).

RESULTS:

Median follow‐up was 2.9 years; median follow‐up on survivors was 3.6 years. Seventy‐nine percent of patients completed ≥6 cycles of chemotherapy; 94% received ≥7200 centigrays. Seven (6%) patients changed from cisplatin to carboplatin because of bone marrow toxicity. Gastrostomy tube feeding was required in 54% of patients either before (16%) or during RT (38%). Two (1.6%) patients died from therapy‐related complications. The 5‐year outcomes were: local control, 83%; locoregional control, 79%; distant metastasis‐free survival, 88%; cause‐specific survival, 76%; and overall survival, 59%. Seven (6%) patients had severe late complications. Three (3%) patients required a permanent gastrostomy tube.

CONCLUSIONS:

Concomitant weekly cisplatin with altered fractionation RT is a safe and effective treatment regimen. Cancer 2010. © 2010 American Cancer Society.     

头颈部鳞癌的术后放疗

头颈部鳞癌术后放疗的临床研究表明术后病理检查结果可作为术后放疗的主要依据；术后放疗与手术的时间间隔是否影响肿瘤的局部控制没有明确证据，但根据放射生物学理论，术后放疗仍宜尽早进行，尤其是具有高危因素的患者；术后放化疗的综合治疗推荐采用同步放化疗，可提高局部控制率、总的生存率和无病生存率，尽管同步放化疗明显增加了急性毒副反应，但远期损伤没有增加，包括第二原发肿瘤：调强收疗（IMRT）和靶向治疗如单克隆抗体C225在头颈部肿瘤术后治疗中的地位和作用有待研究。