Clayton Akazawa

Intensity-modulated radiotherapy in the treatment of nasopharyngeal carcinoma: an update of the UCSF experience

PURPOSE To update our experience with intensity-modulated radiotherapy (IMRT) in the treatment of nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS Between April 1995 and October 2000, 67 patients underwent IMRT for NPC at the University of California-San Francisco (UCSF). There were 20 females and 47 males, with a mean age of 49 (range 17-82). The disease was Stage I in 8 (12%), Stage II in 12 (18%), Stage III in 22 (33%), and Stage IV in 25 (37%). IMRT was delivered using three different techniques: 1) manually cut partial transmission blocks, 2) computer-controlled auto-sequencing segmental multileaf collimator (SMLC), and 3) sequential tomotherapy using a dynamic multivane intensity modulating collimator (MIMiC). Fifty patients received concomitant cisplatinum and adjuvant cisplatinum and 5-FU chemotherapy according to the Intergroup 0099 trial. Twenty-six patients had fractionated high-dose-rate intracavitary brachytherapy boost and 1 patient had gamma knife radiosurgery boost after external beam radiotherapy. The prescribed dose was 65-70 Gy to the gross tumor volume (GTV) and positive neck nodes, 60 Gy to the clinical target volume (CTV), 50-60 Gy to the clinically negative neck, and 5-7 Gy in 2 fractions for the intracavitary brachytherapy boost. Acute and late normal tissue effects were graded according to the Radiation Therapy Oncology Group (RTOG) radiation morbidity scoring criteria. The local progression-free, local-regional progression-free, distant metastasis-free rates, and the overall survival were calculated using the Kaplan-Meier method. RESULTS With a median follow-up of 31 months (range 7 to 72 months), there has been one local recurrence at the primary site. One patient failed in the neck. Seventeen patients developed distant metastases; 5 of these patients have died. The 4-year estimates of local progression-free, local-regional progression-free, and distant metastases-free rates were 97%, 98%, and 66% respectively. The 4-year estimate of overall survival was 88%. The worst acute toxicity documented was as follows: Grade 1 or 2 in 51 patients, Grade 3 in 15 patients, and Grade 4 in 1 patient. The worst late toxicity was Grade 1 in 20 patients, Grade 2 in 15 patients, Grade 3 in 7 patients, and Grade 4 in 1 patient. At 3 months after IMRT, 64% of the patients had Grade 2, 28% had Grade 1, and 8% had Grade 0 xerostomia. Xerostomia decreased with time. At 24 months, only one of the 41 evaluable patients had Grade 2, 32% had Grade 1, and 66% had Grade 0 or no xerostomia. Analysis of the dose-volume histograms (DVHs) showed that the average maximum, mean, and minimum dose delivered were 79.3 Gy, 74.5 Gy, and 49.4 Gy to the GTV, and 78.9 Gy, 68.7 Gy, and 36.8 Gy to the CTV. An average of only 3% of the GTV and 3% of the CTV received less than 95% of the prescribed dose. CONCLUSION Excellent local-regional control for NPC was achieved with IMRT. IMRT provided excellent tumor target coverage and allowed the delivery of a high dose to the target with significant sparing of the salivary glands and other nearby critical normal tissues.

Comparison of treatment plans involving intensity-modulated radiotherapy for nasopharyngeal carcinoma

PURPOSE To compare intensity-modulated radiotherapy (IMRT) treatment plans with conventional treatment plans for a case of locally advanced nasopharyngeal carcinoma. METHODS AND MATERIALS The study case was planned using two types of IMRT techniques, as well as a three-dimensional conformal radiotherapy technique (3D-CRT), and a traditional treatment method using bilateral opposing fields. These four plans were compared with respect to dose conformality, dose-volume histogram (DVH), dose to the sensitive normal tissue structures, and ease of treatment delivery. RESULTS The planned dose distributions were more conformal to the tumor target volume in the IMRT plans than those in the conventional plans. With similar dose coverage of the clinical target volume (CTV), defined as delivery of minimum of 60 Gy to >/= 95% of CTV, the IMRT plans achieved better sensitive normal tissue structure sparing, while concomitantly delivering a minimum dose of 68 Gy to >/= 95% of the gross tumor volume (GTV) at a higher dose per fraction. CONCLUSIONS Compared to conventional techniques, IMRT techniques provide improved tumor target coverage with significantly better sparing of sensitive normal tissue structures in the treatment of locally advanced nasopharyngeal carcinoma. With improvement of the delivery efficiency, IMRT should provide the optimal treatment for all nasopharyngeal carcinoma. Further studies are needed to establish the true clinical advantage of this new modality.

Intensity-modulated radiation therapy for head-and-neck cancer: The UCSF experience focusing on target volume delineation

PURPOSE To review the University of California-San Francisco (UCSF) experience of using intensity-modulated radiation therapy (IMRT) to treat head-and-neck cancer focusing on the importance of target volume delineation and adequate target volume coverage. METHODS AND MATERIALS Between April 1995 and January 2002, 150 histologically confirmed patients underwent IMRT for their head-and-neck cancer at our institution. Sites included were nasopharynx 86, oropharynx 22, paranasal sinus 22, thyroid 6, oral tongue 3, nasal cavity 2, salivary 2, larynx 2, hypopharynx 1, lacrimal gland 1, skin 1, temporal bone 1, and trachea 1. One hundred seven patients were treated definitively with IMRT +/- concurrent platinum chemotherapy (92/107), whereas 43 patients underwent gross surgical resection followed by postoperative IMRT +/- concurrent platinum chemotherapy (15/43). IMRT was delivered using three different techniques: 1) manually cut partial transmission blocks, 2) computer-controlled auto-sequencing segmental multileaf collimator, and 3) sequential tomotherapy using dynamic multivane intensity-modulating collimator. Forty-two patients were treated with a forward plan, 102 patients with an inverse plan, and 6 patients with both forward and inverse plans. The gross target volume (GTV) was defined as tumor detected on physical examination or imaging studies. In postoperative cases, the GTV was defined as the preoperative gross tumor volume. The clinical target volume (CTV) included all potential areas at risk for microscopic tumor involvement by either direct extension or nodal spread including a margin for patient motion and setup errors. The average prescription doses to the GTV were 70 Gy and 66 Gy for the primary and the postoperative cases, respectively. The site of recurrence was determined by the diagnostic neuroradiologist to be either within the GTV or the CTV volume by comparison of the treatment planning computed tomography with posttreatment imaging studies. RESULTS For the primary definitive cases with a median follow-up of 25 months (range 6 to 78 months), 4 patients failed in the GTV. The 2- and 3-year local freedom from progression (LFFP) rates were 97% and 95%. With a median follow-up of 17 months (range 8 to 56 months), 7 patients failed in the postoperative setting. The 2-year LFFP rate was 83%. For the primary group, the average maximum, mean, and minimum doses delivered were 80 Gy, 74 Gy, 56 Gy to the GTV, and 80 Gy, 69 Gy, 33 Gy to the CTV. An average of only 3% of the GTV and 3% of the CTV received less than 95% of the prescribed dose. For the postoperative group, the average maximum, mean, and minimum doses delivered were 79 Gy, 71 Gy, 37 Gy to the GTV and 79 Gy, 66 Gy, 21 Gy to the CTV. An average of only 6% of the GTV and 6% of the CTV received less than 95% of the prescribed dose. CONCLUSION Accurate target volume delineation in IMRT treatment for head-and-neck cancer is essential. Our multidisciplinary approach in target volume definition resulted in few recurrences with excellent LFFP rates and no marginal failures. Higher treatment failure rates were noted in the postoperative setting in which lower doses were prescribed. Potential dose escalation studies may further improve the local control rates in the postoperative setting.

Three-dimensional intensity-modulated radiotherapy in the treatment of nasopharyngeal carcinoma: the University of California–San Francisco experience

PURPOSE To review our experience with three-dimensional intensity-modulated radiotherapy (IMRT) in the treatment of nasopharyngeal carcinoma. METHODS AND MATERIALS We reviewed the records of 35 patients who underwent 3D IMRT for nasopharyngeal carcinoma at the University of California-San Francisco between April 1995 and March 1998. According to the 1997 American Joint Committee on Cancer staging classification, 4 (12%) patients had Stage I disease, 6 (17%) had Stage II, 11 (32%) had Stage III, and 14 (40%) had Stage IV disease. IMRT of the primary tumor was delivered using one of the following three techniques: (1) manually cut partial transmission blocks, (2) computer-controlled autosequencing static multileaf collimator (MLC), and (3) Peacock system using a dynamic multivane intensity-modulating collimator (MIMiC). A forward 3D treatment-planning system was used for the first two methods, and an inverse treatment planning system was used for the third method. The neck was irradiated with a conventional technique using lateral opposed fields to the upper neck and an anterior field to the lower neck and supraclavicular fossae. The prescribed dose was 65-70 Gy to the gross tumor volume (GTV) and positive neck nodes, 60 Gy to the clinical target volume (CTV), and 50-60 Gy to the clinically negative neck. Eleven (32%) patients had fractionated high-dose-rate intracavitary brachytherapy boost to the primary tumor 1-2 weeks following external beam radiotherapy. Thirty-two (91%) patients also received cisplatin during, and cisplatin and 5-fluorouracil after, radiotherapy. Acute and late normal tissue effects were graded according to the Radiation Therapy Oncology Group (RTOG) radiation morbidity scoring criteria. Local-regional progression-free, distant metastasis-free survival and overall survival were estimated using the Kaplan-Meier method. RESULTS With a median follow-up of 21.8 months (range, 5-49 months), the local-regional progression-free rate was 100%. The 4-year overall survival was 94%, and the distant metastasis-free rate was 57%. The worst acute toxicity was Grade 2 in 16 (46%) patients, Grade 3 in 18 (51%) patients and Grade 4 in 1 (3%) patient. The worst late toxicity was Grade 1 in 15 (43%), Grade 2 in 13 (37%), and Grade 3 in 5 (14%) patients. Only 1 patient had a transient Grade 4 soft-tissue necrosis. At 24 months after treatment, 50% of the evaluated patients had Grade 0, 50% had Grade 1, and none had Grade 2 xerostomia. Analysis of the dose-volume histograms (DVHs) showed that the average maximum, mean, and minimum dose delivered were 79.5 Gy, 75.8 Gy, and 56.5 Gy to the GTV, and 78.9 Gy, 71.2 Gy, and 45.4 Gy to the CTV, respectively. An average of only 3% of the GTV and 2% of the CTV received less than 95% of the prescribed dose. The average dose to 5% of the brain stem, optic chiasm, and right and left optic nerves was 48.3 Gy, 23.9 Gy, 15.0 Gy, and 14.9 Gy, respectively. The average dose to 1 cc of the cervical spinal cord was 41.7 Gy. The doses delivered were within the tolerance of these critical normal structures. The average dose to 50% of the right and left parotids, pituitary, right and left T-M joints, and ears was 43. 2 Gy, 41.0 Gy, 46.3 Gy, 60.5 Gy, 58.3 Gy, 52.0 Gy, and 52.2 Gy, respectively. CONCLUSION 3D intensity-modulated radiotherapy provided improved target volume coverage and increased dose to the gross tumor with significant sparing of the salivary glands and other critical normal structures. Local-regional control rate with combined IMRT and chemotherapy was excellent, although distant metastasis remained unabated.

Comparison of treatment plans using intensity-modulated radiotherapy and three-dimensional conformal radiotherapy for paranasal sinus carcinoma

PURPOSE To compare intensity-modulated radiotherapy (IMRT) treatment planning with three-dimensional conformal radiotherapy (3D-CRT) planning for paranasal sinus carcinoma. MATERIALS AND METHODS Treatment plans using traditional 3-field technique, 3D-CRT planning, and inverse planning IMRT were developed for a case of paranasal sinus cancer requiring adjuvant radiotherapy. Plans were compared with respect to dose conformality, dose-volume histograms, doses to critical normal tissues, and ease of treatment delivery. RESULTS The inverse-planned IMRT technique was more conformal around the tumor target volume than conventional techniques. The dose-volume histograms demonstrated significantly better critical normal-tissue sparing with the IMRT plans, while able to deliver a minimum dose of 60 Gy to the clinical tumor volume and 70 Gy to the gross tumor volume. Acute toxicities in our analysis were minimal. CONCLUSIONS IMRT planning provided improved tumor target coverage when compared to 3D-CRT treatment planning. There was significant sparing of optic structures and other normal tissues, including the brainstem. Inverse planning IMRT provided the best treatment for all paranasal sinus carcinomas, but required stringent immobilization criteria. Further studies are needed to establish the true clinical advantage of this modality.

The value of nonuniform margins for six-field conformal irradiation of localized prostate cancer.

PURPOSE Evaluate the hypothesis that by combining nonuniform margins with a technique for limiting the possible extent of posterior motion of the prostate during the delivery of six-field conformal radiotherapy (SFCRT) of the prostate, it is possible to adequately treat the clinical target volume (CTV) and minimize dose to normal structures. METHODS AND MATERIALS Serial computed tomography (CT) scans of prostate patients were taken at 0.5 cm intervals for treatment planning purposes. The initial treatment planning scans were performed with the rectum empty and the bladder full. Subsequent scans were taken at the end of the first week of treatment with the bladder full, but with no attempt to empty the rectum, to mimic the typical treatment situation. The gross tumor volume (GTV), consisting of the prostate and seminal vesicles, as well as the CTV, were defined on the CT images with the aid of a urethrogram to define the inferior border (apex) of the prostate. Variable blocking margins were designed around the CTV using the University of Michigan three dimensional (3D) treatment planning system (UM-PLAN). Isodose distributions displayed on axial, sagittal, coronal, and oblique slices were used to evaluate the adequacy of the various margins applied. Nonuniform margins varying from 0.75 cm posteriorly to 2.0 cm anteriorly and inferiorly were compared to uniform margins of 1.0, 1.5, and 2.0 cm for each patient. Dose volume histograms (DVH) were used to compare doses to the GTV, CTV, rectum, and bladder. RESULTS In a series of 10 patients scanned with the above protocol, treatment plans with nonuniform margins were compared with uniform margins of 1.0, 1.5, and 2.0 cm. Dose-volume histograms showed that nonuniform and 1.0 cm uniform margins deliver the lowest doses to the rectum and bladder, but the use of 1.0 cm uniform margins resulted in inadequate coverage of the CTV in 40% of the cases. The 1.5 and 2.0 cm uniform margins adequately covered the CTV but resulted in significantly higher doses to the bladder and rectum. CONCLUSIONS The use of nonuniform margins, when combined with CT scans performed with the rectum empty and bladder full, can improve tumor control probability while minimizing the risk of morbidity to adjacent critical structures.

Precision radiation therapy for optic nerve sheath meningiomas

A more precise radiation therapy technique to treat unilateral optic nerve sheath meningioma is presented. It uses an immobilization device to align the ipsilateral optic nerve with a vertical axis and employs three small half-beam blocked fields to deliver radiation to a small conformal volume, thereby reducing the dose to the optic chiasm and the contralateral optic nerve. Three patients were successfully treated with this technique, and a fourth patient with optic nerve glioma was also treated in a similar fashion and was included in this study. The new technique irradiates a much smaller volume of tissue to high dose levels: 58 cm3 is irradiated to the 80% isodose level and only 18 cm3 to the 95% level. In contrast, the opposed lateral technique irradiates 171 and 73 cm3 to these levels, respectively. Thus, a considerable reduction in the volume of normal tissue irradiated was accomplished. Doses to the pituitary and contralateral optic nerve were 4% of the treatment dose for the new technique, whereas these doses were 40% and 100% for opposed laterals and 10% and 3% for wedged pair, respectively. The average setup error for this technique was very small, 50% of the setups measured were less than 1 mm off, and 92.5% were less than 3 mm off. However, for the conventional setups without a mask, only 21% of the setups were less than 1 mm off and 55% less than 3 mm off. We recommend this technique for localized unilateral optic nerve sheath meningioma and other optic nerve lesions that may require radiation therapy.

Treatment of the scalp using photon and electron beams

Many problems arise when treating superficial malignancies along the entire scalp. Some techniques will irradiate too much of the underlying brain while others are highly complex and may involve field junction problems. One approach to circumvent such difficulties is to use lateral opposed photon fields and adjoining electron fields as described in this paper. Sufficient dose coverage throughout the entire scalp is achieved, the normal brain tissues receives minimal dosages, the complexities of simulation and treatment are greatly eased, and the ambiguities of doses at field junction regions are diminished.

Dose optimization for the treatment of anaplastic thyroid carcinoma : A comparison of treatment planning techniques

PURPOSE To evaluate and compare dose optimization for the treatment of anaplastic thyroid carcinoma using a 3D conformal plan, and two 3D intensity-modulated inverse plans. METHODS AND MATERIALS After patient immobilization using an alpha cradle and head-mask system, a postoperative CT scan was obtained to delineate the gross tumor volume (GTV), the clinical tumor volume (CTV), and adjacent critical structures. Treatment plans were generated using UM-Plan (University of Michigan), PeacockPlan and Corvus (NOMOS Corporation, Sewickley, PA). Isodoses were displayed in the sagittal, coronal, and multiple axial planes, and dose-volume histograms (DVH) were generated for the GTV, CTV, and critical normal tissues. Treatment times were estimated to compare the practicality of delivering each plan in a busy radiotherapy department. RESULTS All three treatment planning systems were able to deliver a minimum dose of 60 Gy to the GTV while keeping the maximum spinal cord dose at or below 45 Gy. However, there were differences in the doses delivered to 50% and 5% of the cord, the minimum CTV dose, and the overall treatment time. The PeacockPlan best spared the uninvolved tissues of the posterior neck, and provided the lowest dose to the cord without compromising the CTV. CONCLUSIONS Inverse treatment planning provides superior dose optimization for the treatment of anaplastic thyroid carcinoma. The radiobiologic impact of intensity modulation for this tumor should be further tested clinically.

Simplifying intensity-modulated radiotherapy plans with fewer beam angles for the treatment of oropharyngeal carcinoma

The first aim of the present study was to investigate the feasibility of using fewer beam angles to improve delivery efficiency for the treatment of oropharyngeal cancer (OPC) with inverse‐planned intensity‐modulated radiation therapy (IP‐IMRT). A secondary aim was to evaluate whether the simplified IP‐IMRT plans could reduce the indirect radiation dose. The treatment plans for 5 consecutive OPC patients previously treated with a forward‐planned IMRT (FP‐IMRT) technique were selected as benchmarks for this study. The initial treatment goal for these patients was to deliver 70 Gy to ≥95% of the planning gross tumor volume (PTV‐70) and 59.4 Gy to ≥95% of the planning clinical tumor volume (PTV‐59.4) simultaneously. Each case was re‐planned using IP‐IMRT with multiple beam‐angle arrangements, including four complex IP‐IMRT plans using 7 or more beam angles, and one simple IMRT plan using 5 beam angles. The complex IP‐IMRT plans and simple IP‐IMRT plans were compared to each other and to the FP‐IMRT plans by analyzing the dose coverage of the target volumes, the plan homogeneity, the dose–volume histograms of critical structures, and the treatment delivery parameters including delivery time and the total number of monitor units (MUs). When comparing the plans, we found no significant difference between the complex IP‐IMRT, simple IP‐IMRT, and FP‐IMRT plans for tumor target coverage (PTV‐70: p=0.56; PTV‐59.4: p=0.20). The plan homogeneity, measured by the mean percentage isodose, did not significantly differ between the IP‐IMRT and FP‐IMRT plans (p=0.08), although we observed a trend toward greater inhomogeneity of dose in the simple IP‐IMRT plans. All IP‐IMRT plans either met or exceeded the quality of the FP‐IMRT plans in terms of dose to adjacent critical structures, including the parotids, spinal cord, and brainstem. As compared with the complex IP‐IMRT plans, the simple IP‐IMRT plans significantly reduced the mean treatment time (maximum probability for four pairwise comparisons: p=0.0003). In conclusion, our study demonstrates that, as compared with complex IP‐IMRT, simple IP‐IMRT can significantly improve treatment delivery efficiency while maintaining similar target coverage and sparing of critical structures. However, the improved efficiency does not significantly reduce the total number of MUs nor the indirect radiation dose. PACS number: 87.53.tf