P. Xia

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.

Guidance document on delivery, treatment planning, and clinical implementation of IMRT : Report of the IMRT subcommittee of the AAPM radiation therapy committee

Intensity-modulated radiation therapy (IMRT) represents one of the most significant technical advances in radiation therapy since the advent of the medical linear accelerator. It allows the clinical implementation of highly conformal nonconvex dose distributions. This complex but promising treatment modality is rapidly proliferating in both academic and community practice settings. However, these advances do not come without a risk. IMRT is not just an add-on to the current radiation therapy process; it represents a new paradigm that requires the knowledge of multimodality imaging, setup uncertainties and internal organ motion, tumor control probabilities, normal tissue complication probabilities, three-dimensional (3-D) dose calculation and optimization, and dynamic beam delivery of nonuniform beam intensities. Therefore, the purpose of this report is to guide and assist the clinical medical physicist in developing and implementing a viable and safe IMRT program. The scope of the IMRT program is quite broad, encompassing multileaf-collimator-based IMRT delivery systems, goal-based inverse treatment planning, and clinical implementation of IMRT with patient-specific quality assurance. This report, while not prescribing specific procedures, provides the framework and guidance to allow clinical radiation oncology physicists to make judicious decisions in implementing a safe and efficient IMRT program in their clinics.

IMRT commissioning: Multiple institution planning and dosimetry comparisons,a report from AAPM Task Group 119

AAPM Task Group 119 has produced quantitative confidence limits as baseline expectation values for IMRT commissioning. A set of test cases was developed to assess the overall accuracy of planning and delivery of IMRT treatments. Each test uses contours of targets and avoidance structures drawn within rectangular phantoms. These tests were planned, delivered, measured, and analyzed by nine facilities using a variety of IMRT planning and delivery systems. Each facility had passed the Radiological Physics Center credentialing tests for IMRT. The agreement between the planned and measured doses was determined using ion chamber dosimetry in high and low dose regions, film dosimetry on coronal planes in the phantom with all fields delivered, and planar dosimetry for each field measured perpendicular to the central axis. The planar dose distributions were assessed using gamma criteria of 3%/3 mm. The mean values and standard deviations were used to develop confidence limits for the test results using the concept confidence limit = /mean/ + 1.96sigma. Other facilities can use the test protocol and results as a basis for comparison to this group. Locally derived confidence limits that substantially exceed these baseline values may indicate the need for improved IMRT commissioning.

Intensity-Modulated Radiation Therapy With or Without Chemotherapy for Nasopharyngeal Carcinoma: Radiation Therapy Oncology Group Phase II Trial 0225

PURPOSE To investigate the feasibility of intensity-modulated radiation therapy (IMRT) with or without chemotherapy, and to assess toxicities, failure patterns, and survivals in patients with nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS Radiation consisted of 70 Gy given to the planning target volumes of primary tumor plus any N+ disease and 59.4 Gy given to subclinical disease, delivered over 33 treatment days. Patients with stage T2b or greater or with N+ disease also received concurrent cisplatin (100 mg/m(2)) on days 1, 22, and 43 followed by adjuvant cisplatin (80 mg/m(2)) on day 1; fluorouracil (1,000 mg/m(2)/d) on days 1 through 4 administered every 4 weeks for three cycles. Tumor, clinical status, and acute/late toxicities were assessed. The primary objective was to test the transportability of IMRT to a multi-institutional setting. RESULTS Between February 2003 and November 2005, 68 patients with stages I through IVB NPC (of which 93.8% were WHO types 2 and 3) were enrolled. Prescribed IMRT (target delineation) was given to 83.8%, whereas 64.9% received chemotherapy per protocol. The estimated 2-year local progression-free (PF), regional PF, locoregional PF, and distant metastasis-free rates were 92.6%, 90.8%, 89.3%, and 84.7%, respectively. The estimated 2-year PF and overall survivals were 72.7% and 80.2%, respectively. Acute grade 4 mucositis occurred in 4.4%, and the worst late grade 3 toxicities were as follows: esophagus, 4.7%; mucous membranes, 3.1%; and xerostomia, 3.1%. The rate of grade 2 xerostomia at 1 year from start of IMRT was 13.5%. Only two patients complained of grade 3 xerostomia, and none had grade 4 xerostomia. CONCLUSION It was feasible to transport IMRT with or without chemotherapy in the treatment of NPC to a multi-institutional setting with 90% LRPF rate reproducing excellent reports from single institutions. Minimal grade 3 and lack of grade 4 xerostomia were encouraging.

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.

Skin toxicity due to intensity-modulated radiotherapy for head-and-neck carcinoma

PURPOSE To investigate the cause of acute skin toxicity observed in the treatment of head-and-neck cancer with extended-field intensity-modulated radiotherapy (EF-IMRT). METHODS AND MATERIALS EF-IMRT was used to treat head-and-neck cancer, with the gross target volume receiving 70 Gy and the clinical target volume 60 Gy. A thermoplastic mask covering the head, neck, and shoulder was used for immobilization. Dosimetric studies were conducted to investigate the possible causes of the skin reactions, such as the bolus effect of the mask, the use of multiple tangential beams with IMRT plans, and the way in which the physicians contoured the lymph nodes. The dose-volume histograms of conventional opposed-lateral fields were compared with that of the multiple tangential EF-IMRT fields. IMRT plans with neck nodes contoured up to and including the skin surface were compared with plans that contoured the neck nodes 5 mm away from the skin surface. In addition, IMRT plans defining the skin as a sensitive structure were compared with plans that did not define the skin as a sensitive structure. All plans were created using an anthropomorphic Rando phantom, and the skin doses were measured with and without the mask. In each measurement, 6 thermoluminescent dosimeters (TLDs) were placed at the lateral and medial surfaces of the neck. RESULTS For all four plans, the measured skin doses with the mask were consistently higher than those without the mask. The average dose increase was about 18% owing to the bolus effect of the mask. Multiple tangential fields used in IMRT plans contributed to an increase in skin dose by about 19% and 27%, with and without the mask, respectively. If the skin of the neck was contoured as a sensitive structure for dose optimization, the volume of skin that received >45 Gy was further reduced by about 20%. Five patients immobilized with head and shoulder masks were treated with EF-IMRT plans with the neck nodes carefully delineated away from the skin surface. The neck skin was identified as a sensitive structure for dose optimization. Grade 1 toxicity was observed in 3 patients, Grade 2 in 1 patient, and Grade 3 in 1 patient toward the end of treatment. CONCLUSION Multiple factors contributed to the observed acute skin reaction for head-and-neck cancer patients treated with EF-IMRT. By taking into consideration the skin as a sensitive structure during inverse planning, it was possible to reduce the skin dose to a tolerable level without compromising tumor target coverage.

Investigation of the use of MOSFET for clinical IMRT dosimetric verification

(Received 22 October 2001; accepted for publication 26 March 2002; published 22 May 2002) With advanced conformal radiotherapy using intensity modulated beams, it is important to have radiation dose verification measurements prior to treatment. Metal oxide semiconductor field effect transistors (MOSFET) have the advantage of a faster and simpler reading procedure compared to thermoluminescent dosimeters (TLD), and with the commercial MOSFET system, multiple detectors can be used simultaneously. In addition, the small size of the detector could be advantageous, especially for point dose measurements in small homogeneous dose regions. To evaluate the feasibility of MOSFET for routine IMRT dosimetry, a comprehensive set of experiments has been conducted, to investigate the stability, linearity, energy, and angular dependence. For a period of two weeks, under a standard measurement setup, the measured dose standard deviation using the MOSFETs was +/- 0.015 Gy with the mean dose being 1.00 Gy. For a measured dose range of 0.3 Gy to 4.2 Gy, the MOSFETs present a linear response, with a linearity coefficient of 0.998. Under a 10 x 10 cm2 square field, the dose variations measured by the MOSFETs for every 10 degrees from 0 to 180 degrees is +/- 2.5%. The percent depth dose (PDD) measurements were used to verify the energy dependence. The measured PDD using the MOSFETs from 0.5 cm to 34 cm depth agreed to within +/- 3% when compared to that of the ionization chamber. For IMRT dose verification, two special phantoms were designed. One is a solid water slab with 81 possible MOSFET placement holes, and another is a cylindrical phantom with 48 placement holes. For each IMRT phantom verification, an ionization chamber and 3 to 5 MOSFETs were used to measure multiple point doses at different locations. Preliminary results show that the agreement between dose measured by MOSFET and that calculated by Corvus is within 5% error, while the agreement between ionization chamber measurement and the calculation is within 3% error. In conclusion, MOSFET detectors are suitable for routine IMRT dose verification.

Forward or inversely planned segmental multileaf collimator imrt and sequential tomotherapy to treat multiple dominant intraprostatic lesions of prostate cancer to 90 Gy

PURPOSE To investigate the technical feasibility of using forward or inversely planned segmental multileaf collimator (SMLC) intensity-modulated radiotherapy and sequential tomotherapy (ST) to escalate to a dose of 90 Gy to multiple dominant intraprostatic lesions within the prostate gland while delivering a dose of 75.6 Gy to the remaining prostate. METHODS AND MATERIALS A selected case with one dominant intraprostatic lesion located at the left base and a second dominant intraprostatic lesion at the right apex of the prostate was planned using three different intensity modulation techniques. Two plans were generated with inverse treatment planning, using either SMLC or ST with a special multivane collimator. The third plan also employed SMLC but was generated using forward planning. All three plans were compared based on dose-volume histograms, isodose distributions, and doses to sensitive normal structures. RESULTS All three plans meet and exceed the desired dose constraints, limiting doses to the rectum and bladder to an estimated RTOG Grade 2 complication rate of <10%. The ST plan achieved the best dose conformality, whereas the inverse SMLC plan gave the lowest dose to the rectal wall, and the forward SMLC plan obtained the best dose homogeneity inside the targets. CONCLUSIONS Using any of the three intensity-modulated techniques, it is technically feasible to concurrently treat multiple selected high-risk regions within the prostate to 90 Gy and the remaining prostate to 75.6 Gy, while keeping the doses to the rectum and the bladder significantly lower than those associated with a Grade 2 complication rate of 10%.