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.     

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.     

Accelerated treatment using intensity‐modulated radiation therapy plus concurrent capecitabine for unresectable hepatocellular carcinoma

BACKGROUND:

Patients with unresectable hepatocellular carcinoma (HCC) have limited treatment options. In this study, the authors investigated the feasibility, toxicity, and efficacy associated with intensity‐modulated radiation therapy (IMRT) and concurrent, chronomodulated capecitabine in the treatment of unresectable HCC.

METHODS:

Twenty patients underwent treatment planning for HCC confined to the liver with helical tomotherapy‐based IMRT. Fifty‐five percent of patients had Child‐Pugh Class A disease, and 45% of patients had Class B disease. Ninety‐five percent of patients were prescribed 50 gray (Gy) of radiotherapy to the planning target volume delivered in 20 fractions with concurrent, chronomodulated capecitabine. Transcatheter arterial chemoembolization preceded radiotherapy in 11 patients, and 9 patients received IMRT alone because of portal vein thrombosis, esophageal varices, or tumor size.

RESULTS:

The mean greatest tumor dimension was 9 cm (range, 1.3‐17.4 cm), the mean dose to normal liver was 22.6 Gy (range, 10‐29.2 Gy), and the average volume of liver that received >30 Gy (V30) was 27.2% (range, 12%‐43%). Eighteen patients (90%) completed the prescribed treatment of 50 Gy. There was no increase from baseline in acute or late toxicity greater than 2 grades. Partial response or disease stability was achieved at 3 months to 6 months after treatment in 15 of 16 patients (94%). The median survival (±standard deviation) for patients who had Child‐Pugh Class A and B disease was 22.5 ± 5.1 months and 8 ± 3.3 months, respectively.

CONCLUSIONS:

In this initial experience with accelerated IMRT plus capecitabine for patients who had large HCC lesions, the results demonstrated acceptable toxicity with promising local control. The relatively low acute and late toxicity observed with this program suggested that dose intensification can be incorporated into the treatment regimen if needed. Cancer 2009. © 2009 American Cancer Society.     

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.     

Phase 2 study of preoperative image‐guided intensity‐modulated radiation therapy to reduce wound and combined modality morbidities in lower extremity soft tissue sarcoma

BACKGROUND:

This study sought to determine if preoperative image‐guided intensity‐modulated radiotherapy (IG‐IMRT) can reduce morbidity, including wound complications, by minimizing dose to uninvolved tissues in adults with lower extremity soft tissue sarcoma.

METHODS:

The primary endpoint was the development of an acute wound complication (WC). IG‐IMRT was used to conform volumes to avoid normal tissues (skin flaps for wound closure, bone, or other uninvolved soft tissues). From July 2005 to June 2009, 70 adults were enrolled; 59 were evaluable for the primary endpoint. Median tumor size was 9.5 cm; 55 tumors (93%) were high‐grade and 58 (98%) were deep to fascia.

RESULTS:

Eighteen (30.5%) patients developed WCs. This was not statistically significantly different from the result of the National Cancer Institute of Canada SR2 trial (P = .2); however, primary closure technique was possible more often (55 of 59 patients [93.2%] versus 50 of 70 patients [71.4%]; P = .002), and secondary operations for WCs were somewhat reduced (6 of 18 patients [33%] versus 13 of 30 patients [43%]; P = .55). Moderate edema, skin, subcutaneous, and joint toxicity was present in 6 (11.1%), 1 (1.9%), 5 (9.3%), and 3 (5.6%) patients, respectively, but there were no bone fractures. Four local recurrences (6.8%, none near the flaps) occurred with median follow‐up of 49 months.

CONCLUSIONS:

The 30.5% incidence of WCs was numerically lower than the 43% risk derived from the National Cancer Institute of Canada SR2 trial, but did not reach statistical significance. Preoperative IG‐IMRT significantly diminished the need for tissue transfer. RT chronic morbidities and the need for subsequent secondary operations for WCs were lowered, although not significantly, whereas good limb function was maintained. Cancer 2013. © 2013 American Cancer Society.     

Constrained‐beam inverse planning for intensity‐modulated radiation therapy of prostate cancer patients with bilateral hip prostheses

Hip prostheses present a technical challenge in the planning of curative external beam radiation treatment for patients with prostate cancer. Bilateral prostheses compel planners to compromise between target coverage and avoidance of beam entry through the prostheses. Inverse planning systems given objectives to avoid dose to prostheses are overly restricted from allowing exit dose to them. We report a novel inverse planning technique for intensity‐modulated radiation therapy of patients with prostate cancer and bilateral hip prostheses, by constraining beam characteristics rather than dose in the inverse planning process.     

Phase 2 trial of concurrent 5‐fluorouracil,hydroxyurea, cetuximab,and hyperfractionated intensity‐modulated radiation therapy for locally advanced head and neck cancer

BACKGROUND:

The objective of this phase 2 study was to evaluate the tolerability and efficacy of incorporating cetuximab and simultaneous integrated‐boost (SIB), intensity‐modulated radiation therapy (IMRT) into a well described 5‐fluorouracil (5‐FU) and hydroxyurea (HU)‐based chemoradiation regimen.

METHOD:

Patients with stage IVA and IVB or high‐risk stage III squamous cell carcinomas of the head and neck were enrolled on a phase 2 trial. Prior organ‐conserving surgery or induction chemotherapy was allowed off protocol. SIB‐IMRT was prescribed to low‐risk volumes (43.2 gray [Gy] to 48 Gy) and intermediate‐risk volumes (54‐63 Gy). A separate IMRT cone‐down plan was targeted to macroscopic disease (72 Gy). The median radiation dose was 72 Gy (range, 60‐72 Gy) administered in 1.5 Gy fractions twice daily during Weeks 1, 3, 5, 7 and 9. Concurrent systemic therapy consisted of 5‐FU (600 mg/m²), HU (500 mg twice daily), and cetuximab (250 mg/m²).

RESULTS:

From January 2007 through April 2008, 33 patients were enrolled. At a median follow‐up of 24 months, the 2‐year rates of locoregional control, distant control, disease‐free survival, and overall survival were 83%, 79%, 69%, and 86%, respectively. Grade 3 toxicity consisted of mucositis in 33% of patients, radiation dermatitis in 15%of patients, anemia in 18% of patients, leukopenia in 18% of patients, neutropenia in 12% of patients, and thrombocytopenia in 3% of patients. Most patients (64%) were able to tolerate treatment without a feeding tube, and there were no acute or late grade ≥4 adverse events.

CONCLUSIONS:

The current results indicated that concurrent 5‐FU, HU, and cetuximab plus SIB‐IMRT is a promising and reasonably well tolerated approach to incorporating molecularly targeted therapy into curative therapy for patients with locally advanced head and neck cancer. Cancer 2011. © 2010 American Cancer Society.     

前列腺癌调强放疗的治疗方案比较

目的 通过对前列腺癌调强放疗的多种布野方案比较，确定符合临床要求的最佳方案。方法 对8例前列腺癌患者采用调强放疗方案，处方总剂量76Gy。共设计7个计划，其中共面布野方案5个，分别为5、6、7、9野均匀分布和7野非均匀分布；非共面布野方案2个，分别为5、7野冠状交角照射。分别比较它们的剂量分布、剂量体积直方图、适形度指数等指标。结果 所有7个共面和非共面计划的计划靶区剂量分布无明显差别，非共面计划比共面计划降低了直肠D59(50％体积所受剂量)剂量23％，但增加了股骨头剂量，膀胱的剂量大致相同；同时非共面计划还延长了治疗时间，摆位较麻烦。对于共面射野计划，当射野数目由5增至7时，增加照射野数目对靶区、直肠和膀胱剂量分布没有改善且会增加治疗时间，但能降低股骨头受量，靶区剂量均匀性、适合度指数提高，5、6野情况大致相同。当射野数由7野增加到9野时，股骨头受量和靶区剂量均匀性、适合度均无改善。结论 5～7野共面调强计划可使前列腺肿瘤获得理想的剂量分布，共面、等角度分布的照射野设计简单、治疗实施效率高。非共面计划射野从5野增加到7野，剂量分布无改善。     

Cetuximab or nimotuzumab plus intensity‐modulated radiotherapy versus cisplatin plus intensity‐modulated radiotherapy for stage II‐IVb nasopharyngeal carcinoma

To compare intensity‐modulated radiotherapy (IMRT) with cisplatin (CDDP) versus cetuximab (CTX) and nimotuzumab (NTZ) for Stage II‐IVb Nasopharyngeal Carcinoma (NPC). A total of 1,837 patients with stage II – IV_b NPC who received IMRT plus CTX or NTZ, or CDDP between January 2009 and December 2013 were included in the current analysis. Using propensity scores to adjust for potential prognostic factors, a well‐balanced cohort of 715 patients was created by matching each patient who underwent IMRT plus concomitant NTZ/CTX with four patients who underwent IMRT plus concomitant CDDP (1:4). Efficacy and safety were compared between the CTX/NTZ and CDDP groups of this well‐balanced cohort. Furthermore, we conducted multivariate analysis and subgroup analysis based on all the 1,837 eligible cases. There was no significant difference between CTX/NTZ group and CDDP group in terms of DFS (3‐year, 86.7% vs. 86.2%, p > 0.05), LRRFS (96.2% vs. 96.3%, p > 0.05), DMFS (91.1% vs. 92.3%, p > 0.05) and OS (91.7% vs. 91.9%, p > 0.05). Subgroup analysis demonstrated a significant interaction effect between patients with IMRT plus CTX/NTZ and N3 node stage on LRRFS with the highest risk of loco‐regional relapse (HR 8.85, p = 0.001). Significantly increased hematologic toxicities, gastrointestinal reactions were observed in the CDDP group (p < 0.05). Patients of 3.4 – 4.7% experienced severe hematologic toxicities during the treatment with concomitant CTX and NTZ. Increased rate of CTX related‐skin reaction and mucositis was observed in the CTX group. CTX/NTZ used concurrently with IMRT may be comparable to those of the standard CDDP‐IMRT combination for maximizing survival for patients with stage II‐IVb NPC.     

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.     

Comparison of intensity‐modulated radiotherapy and 3‐dimensional conformal radiotherapy as adjuvant therapy for gastric cancer

BACKGROUND:

The current study was performed to compare the clinical outcomes and toxicity in patients treated with postoperative chemoradiotherapy for gastric cancer using intensity‐modulated radiotherapy (IMRT) versus 3‐dimensional conformal radiotherapy (3D CRT).

METHODS:

Fifty‐seven patients with gastric or gastroesophageal junction cancer were treated postoperatively: 26 with 3D CRT and 31 with IMRT. Concurrent chemotherapy was capecitabine (n = 31), 5‐fluorouracil (5‐FU) (n = 25), or none (n = 1). The median radiation dose was 45 Gy. Dose volume histogram parameters for kidney and liver were compared between treatment groups.

RESULTS:

The 2‐year overall survival rates for 3D CRT versus IMRT were 51% and 65%, respectively (P = .5). Four locoregional failures occurred each in the 3D CRT (15%) and the IMRT (13%) patients. Grade ≥2 acute gastrointestinal toxicity was found to be similar between the 3D CRT and IMRT patients (61.5% vs 61.2%, respectively) but more treatment breaks were needed (3 vs 0, respectively). The median serum creatinine from before radiotherapy to most recent creatinine was unchanged in the IMRT group (0.80 mg/dL) but increased in the 3D CRT group from 0.80 mg/dL to 1.0 mg/dL (P = .02). The median kidney mean dose was higher in the IMRT versus the 3D CRT group (13.9 Gy vs 11.1 Gy; P = .05). The median kidney V20 was lower for the IMRT versus the 3D CRT group (17.5% vs 22%; P = .17). The median liver mean dose for IMRT and 3D CRT was 13.6 Gy and 18.6 Gy, respectively (P = .19). The median liver V30 was 16.1% and 28%, respectively (P < .001).

CONCLUSIONS:

Adjuvant chemoradiotherapy was well tolerated. IMRT was found to provide sparing to the liver and possibly renal function. Cancer 2010. © 2010 American Cancer Society.