Tolerance of pelvic normal tissues to hyperfractionated radiation therapy: results of Protocol 83-08 of the Radiation Therapy Oncology Group

A prospective, centrally randomized Phase I/II trial of hyperfractionation in definitive radiation therapy for locally advanced squamous and transitional cell carcinoma of the bladder was conducted by the Radiation Therapy Oncology Group (RTOG) from April 1983 through June 1986. Patients with T3-4 and T2 N+ (AJC) histologically-confirmed cancer of the bladder received twice daily radiation therapy with 1.2 Gy per fraction and a minimum of 4 hr between fractions. All patients received a whole pelvic total dose of 50.4 Gy: Total doses to reduced volumes were 60.0 Gy, 64.8 Gy, or 69.6 Gy. Of 54 patients entered, 50 were eligible. An unbalanced treatment assignment was used: Nine patients received 60.0 Gy, 15 patients received 64.8 Gy and 26 received 69.6 Gy. Performance status (Karnofsky) was 90-100 in 72% of patients and 92% had transitional carcinoma. Eighty percent of tumors were T3 or T4. Observation of at least 18 months was available for 26 patients. Grade 3 acute reactions (within 90 days) were reported in eight patients (one at 60.0 Gy, three at 64.8 Gy and four at 69.6 Gy). Five patients experienced a total of seven major late effects--four Grade 3 and three Grade 4. The cumulative probability of Grade 3 and 4 late complications of treatment for the 46 patients at risk for late complications was 5% +/- 3% at 6 months, 7% +/- 4% at 12 months, and 10% +/- 5% at 18 and 24 months. The cumulative probability of Grade 3 or 4 late complications for patients who received a total dose of 69.6 Gy was 5% +/- 4% at 6 and 12 months and 11% +/- 8% at 18 and 24 months. Only one patient who experienced major late effects was also reported to have major acute reactions. Comparisons of survival of patients treated in the current study with those who received 60 Gy in 30 fractions in 6 weeks in RTOG Protocol 71-04, did not suggest any deleterious effects from hyperfractionated radiation therapy to the pelvis. The normal pelvic tissues tolerated hyperfractionated radiation therapy sufficiently well to justify exploring it, alone and with brachytherapy, in other pelvic tumors.     

Brachytherapy: Results of two different therapy strategies for patients with primary glioblastoma multiforme

BACKGROUND: In the current study, the authors describe and compare two different strategies of brachytherapy for the treatment of patients with primary glioblastoma multiforme (GBM). METHODS: The study was comprised of 84 patients. Forty-five patients were implanted with permanent or temporary low activity iodine-125 ((125)I) seeds in Cologne and 21 patients were implanted with temporary iridium-192 ((192)Ir) wires in Amsterdam. Both groups received external beam radiation therapy (EBRT); the (125)I group received 10-30 grays (Gy) with the implant in situ and the (192)Ir group received 60 Gy before implantation. In Cologne, implantation was performed after a diagnostic stereotactic biopsy whereas in Amsterdam implantation took place after cytoreductive diagnostic surgery. In addition, 18 patients in Amsterdam served as a control group. This group received only EBRT after cytoreductive surgery. RESULTS: In both groups the mean age of the patients was between 50-55 years, with 80% of the patients age > 45 years. The mean implantation volume encompassed by the referenced isodose was 23 cm(3) for (125)I and 48 cm(3) for (192)Ir. Initial dose rates were 2. 5-2.9 centigrays (cGy)/hour for permanent (125)I, 4.6 cGy/hour for temporary (125)I, and 44-100 cGy/hour (mean, 61 cGy) for (192)Ir. A total dose of 50-60 Gy, 60-80 Gy, and 40 Gy, respectively, was administered at the outer margins of the tumor. The median survival was approximately 16 months for both the (125)I group and the (192)Ir group. This was 6 months longer than the median survival in the control group. Reoperations were performed in 4 patients in the (125)I group (9%) versus 7 patients in the (192)Ir group (33%). No complications or late reactions were reported in the (125)I group, whereas one case of hemorrhage and three cases of delayed stroke were observed in the (192)Ir group. CONCLUSIONS: The equal median survival times in these two brachytherapy groups with such different dose rate radiation schedules support the hypothesis that dose rate does not play a major role in the survival of patients with primary GBM.     

A cost-minimising analysis of standard radiotherapy and two experimental therapies in glioblastoma.

BACKGROUND AND PURPOSE: Accelerated radiotherapy (ART) and intracavity brachytherapy (ICBT) have been introduced in the primary treatment of glioblastoma. Our objective was to determine total treatment costs, hospitalisation time, and treatment outcome in these two experimental therapies compared to standard treatment. MATERIALS AND METHODS: In the time period 1985 to 1st May 1999, a total of 174 patients with histologically confirmed glioblastoma multiforme were given postoperative radiotherapy according to three different treatment schedules at three different time intervals. A conventional regime of external radiotherapy (54Gy/30 fractions) was given to 58 patients (group I), 75 patients were treated with ART (48Gy/twice daily 30 fractions) (group II), and 41 patients were given ICBT (60Gy/ten fractions) (group III). Treatment costs including surgery, hospital stay, hospital hotel stay, and radiotherapy were calculated. RESULTS: The total mean costs employing the three treatment alternatives were calculated to $25,618 (group I), $23,442 (group II), and $14,534 (group III). Total mean stay in hospital for the whole primary treatment was 48.8, 41.6, and 19 days for groups I, II, and III respectively. Median survival figures were 16, 14, and 13 months for groups I, II, and III, respectively. CONCLUSIONS: The total cost of postoperative radiotherapy in glioblastoma is comparable to other health care services. ART did not improve the total treatment cost or influence the need for hospitalisation compared to standard treatment. ICBT seemed to have economic benefits with less need for hospitalisation.     

Early stage nasopharyngeal carcinoma: radiotherapy dose and time factors in tumor control

OBJECTIVE: To evaluate radiotherapy dose and length of treatment in the control of early stage nasopharyngeal carcinoma (NPC) treated with a combination of external radiotherapy and brachytherapy, MATERIALS & METHODS: We reviewed the records of 133 patients with early stage nasopharyngeal carcinoma (stage I or II, AJC/UICC staging system) who received definitive radiotherapy in Chang Gung Memorial Hospital from 1979 to 1991. The median follow-up time was 7.1 years with a minimum of 2 years. All patients were treated with megavoltage external radiotherapy to the nasopharynx area (63-72 Gy) followed by high dose rate intracavitary brachytherapy (5-16.5 Gy in one to three fractions, spaced 1-2 weeks apart). The median total dose and time of irradiation was 75 Gy (69.8-81.4 Gy) and 11.6 weeks (7.8-20 weeks) respectively. Survival analysis was used to examine the effect of several variables on prognosis. RESULTS: The 5-year rates were 86.4% for local control, 84.7% for disease free survival, 88.5% for actuarial survival and 84.2% for overall survival. The treatment group (combination of time and dose of irradiation) was the most important prognostic factor according to Cox's proportional hazard model. Patients receiving radiation at a total dose of < or = 75 Gy completed in < 12 weeks showed the best prognosis. CONCLUSION: Treatment time and total treatment dose are both important factors in treating early stage NPC. Decreasing the total radiation time to < 12 weeks and not exceeding a radiation dose of 75 Gy gave the best results.      

Fractionation in medium dose rate brachytherapy of cancer of the cervix

: To established an optimum fractionation for medium dose rate (MDR) brachytherapy from retrospective data of patients treated with different MDR schedules in comparison with a low dose rate (LDR) schedule.

: The study population consists of consecutive Stage IB-IIA-IIB patients who received radiotherapy alone with full dose brachytherapy plus external beam pelvic and parametrial irradiation from 1986–1993. Patients also receiving surgery or chemotherapy were excluded. The LDR group (n = 102, median follow-up: 80 months) received a median dose to Point A of 32.5 Gy fractions at 0.44 Gy/h plus 18 Gy of external whole pelvic irradiation. The MDR1 group (n = 30, median follow-up: 45 months) received a mean dose of two 32 Gy fractions at 1.68 Gy/h. An individual dose reduction of 12.5% was planned for this group according to the Manchester experience, but only a 4.8% dose reduction was achieved. The MDR2 group (n = 10, median follow-up: 36 months) received a dose of two 24 Gy fractions at 1.65 Gy/h. The MDR3 group (n = 10, median follow-up 33 months_ received a mean dose of three 15.3 Gy fractions at 1.64 Gy/h. And finally, the MDR4 group (n = 38, median follow-up: 24 months)_received six six 7.7 Gy fractions from two pulses 6 h apart in each of three insertions at 1.61 Gy/h/ The median external pelvic dose to MDR schedules was between 12 and 20 Gy. The linear quadratic (LQ) formula was used to calculate the biologically effective dose (BED) to tumor (BED) to tumor (Gy₁₀) and rectum (Gy₃), assuming T1/2 for REPAIR = 1.5 h.

: The crude central recurrence rate was 6% for LDR (mean BED - 95.4 Gy₁₀) and 10% for MDR4 (mean BED = 77.0 Gy₁₀ (p = NS). The remaining MDR groups had no recurrences. Grade 2 and 3 rectal or bladder complications were 0% for LDR (rectal BED = 109 Gy₃), 83% for MDR1 (BED = 206 Gy₃), and 30% for MDR3 (BED = 127 Gy₃). The MDR2 and MDR4 groups presented no complications (BED, 123 Gy₃, and 105 Gy₃, respectively). The LQ formula appears to correlate with late complications of the different MDR regimens. A BED above 125 Gy₃ was associated with Grade 2+3 rectal complications. Adequate central tumor control may be compromised with a tumor BED below 90–95 Gy₁₀.

: Medium dose rate brachytherapy at 1.6 Gy/h to point A has a marked dose ratre effect. Increased fractionation is the cost of overcoming the less favorable therapeutic ratio for MDR than for LDR. A larger (25%) reduction of brachytherapy dose than previously reported is also necessary. Our most recently developed schedule for Stage I–II patients is three insertions on three treatment days with six 8.0 Gy brachytherapy fractions, two on each treatment day, following or preceding an external whole pelvis dose of 18 Gy, and followed by additional external parametrial dose.     

Dosimetry and radiobiologic model comparison of IMRT and 3D conformal radiotherapy in treatment of carcinoma of the prostate

INTRODUCTION: Intensity-modulated radiotherapy (IMRT) has introduced novel dosimetry that often features increased dose heterogeneity to target and normal structures. This raises questions of the biologic effects of IMRT compared to conventional treatment. We compared dosimetry and radiobiologic model predictions of tumor control probability (TCP) and normal tissue complication probability (NTCP) for prostate cancer patients planned for IMRT as opposed to standardized three-dimensional conformal radiotherapy (3DCRT). METHODS AND MATERIALS: Segmented multileaf collimator IMRT treatment plans for 32 prostate cancer patients were compared to 3DCRT plans for the same patients. Twenty-two received local-field irradiation (LFI), and 10 received extended-field irradiation (EFI) that included pelvic lymph nodes. For LFI, IMRT was planned for delivery of 2 Gy minimum dose to the prostate (> or =99% volume coverage) for 35 fractions. The 3DCRT plans, characterized by more homogenous dose to the target, were designed according to a different protocol to deliver 2 Gy to the center of the prostate for 37 fractions. Mean total dose from 35 fractions of IMRT was equal to mean total dose from 37 fractions of 3DCRT. For EFI, both IMRT and 3DCRT were planned for 2 Gy per fraction to a total dose of 50 Gy to prostate and pelvic lymph nodes, followed by 2 Gy per fraction to 20 Gy to the prostate alone. Treatment dose for EFI-IMRT was defined as minimum dose to the target, whereas for EFI-3DCRT, it was defined as dose to the center of the prostate. TCP was calculated for the prostate in the linear-quadratic model for two choices of alpha/beta. NTCP was calculated with the Lyman model for organs at risk, using Kutcher-Burman dose-volume histogram reduction with Emami parameters. RESULTS AND CONCLUSIONS: Dose to the prostate, expressed as mean +/- standard deviation, was 74.7 +/- 1.1 Gy for IMRT vs. 74.6 +/- 0.3 Gy for 3D for the LFI plans, and 74.8 +/- 0.6 Gy for IMRT vs. 71.5 +/- 0.6 Gy for 3D for the EFI plans. For the studied protocols, TCP was greater for IMRT than for 3D across the full range of target sensitivity, for both localized- and extended-field irradiation. For LFI, this was due to the smaller number of fractions (35 vs. 37) used for IMRT, and for EFI, this was due to the greater mean dose for IMRT, compared to 3D. For all organs, mean NTCP tended to be lower for IMRT than for 3D, although NTCP values were very small for both 3D and IMRT. Differences were statistically significant for rectum (LFI and EFI), bladder (EFI), and bowel (EFI). For both LFI and EFI, the calculated NTCPs qualitatively agreed with early published clinical data comparing genitourinary and gastrointestinal complications of IMRT and 3D. Present calculations support the hypothesis that accurately delivered IMRT for prostate cancer can limit dose to normal tissue by reducing treatment margins relative to conventional 3D planning, to allow a reduction in complication rate spanning several sensitive structures while maintaining or increasing tumor control probability.     

Local tumor control and morbidity after one to three fractions of stereotactic external beam irradiation for uveal melanoma.

BACKGROUND AND PURPOSE: To evaluate prospectively local tumor control and morbidity after 1-3 fractions of stereotactic external beam irradiation (SEBI) in patients with uveal melanoma, unsuitable for ruthenium-106 brachytherapy or local resection. MATERIAL AND METHODS: This phase I/II study includes 62 selected patients with uveal melanoma. The mean initial tumor height was 7.8+/-2.8 mm. With the Leskell gamma knife SEBI, 41 patients (66%) were irradiated with two equal fractions of 35, 30 or 25 Gy/fraction, 14 patients (22%) were treated with three fractions of 15 Gy each, and seven patients (11%) with small tumor volumes below 400 mm(3) were treated with one fraction of 45 Gy. The mean total dose was 54+/-8 Gy. The minimal follow-up period was 12 months, and the median follow-up was 28.3 months. Data on radiation-induced side-effects were analyzed with the Cox proportional hazards model for possible risk factors. RESULTS: Local tumor control was achieved in 98% and tumor height reduction in 97%. The mean relative tumor volume reductions were 44, 60 and 72% after 12, 24 and 36 months, respectively. Seven patients developed metastases (11%). Secondary enucleation was performed in eight eyes (13%). Morbidity was significant in tumors exceeding 8 mm in initial height; it was comparable and acceptable in those smaller. In the stepwise multiple Cox model, tumor localization, height and volume, planning target volume (PTV), total dose and patient age were identified as the strongest risk factors for radiation-induced lens opacities, secondary glaucoma, uveitis, eyelash loss and exudative retinal detachment. In this model, the high-dose volume irradiated with more than 10 Gy/fraction was the strongest risk factor for radiation-induced uveitis. CONCLUSIONS: Stereotactic external photon beam irradiation and a total dose of 45-70 Gy delivered in one to three fractions are highly effective at achieving local tumor control in uveal melanoma. Further clinical studies using smaller fraction doses, and consequent smaller high-dose volumes, are justified to optimize dose and fractionation. Fractionated stereotactic irradiation has a challenging potential as an eye-preserving treatment in uveal melanoma.     

Evaluation of level I and II axillary nodes included in the standard breast tangential fields and calculation of the administered dose: results of a prospective study

PURPOSE: To evaluate if Level I and II axillary nodes are included in the standard breast tangential fields, and to calculate the dose administered. METHODS AND MATERIALS: In 35 patients treated with conservative surgery and axillary dissection, three clips were surgically positioned: one at the beginning of Level I, one between Level I and II, and another at the end of Level II. The breast was irradiated with two tangential fields. On simulation films, the volume between the clips was scored as "entirely included" or "not entirely included" in the treatment fields. Computed tomography (CT) scans were performed; CT data were imported into a treatment planning system, and three-dimensional plans were devised. Axillary Levels I and II were delineated on CT slices on the basis of anatomic landmarks. Fields and isodose curves previously obtained were superimposed to calculate the dose administered to the first two axillary node levels and to 90% of both volumes. RESULTS: On X-rays, the volume between clips corresponding to Level I was completely included in the medial field in 66.7% of cases and in the lateral field in 63.7% of cases, whereas the volume of Level II was entirely included in the medial field in 54.5% of cases and in the lateral field in 45.4% of cases. The median dose administered to Level I and II was 38.58 Gy +/- 11.01 (range 3.46-47.14) and 20.65 Gy +/- 14.07 (range 0.95-38.94), respectively. The median dose to 90% of both volumes of Level I and II was 6.75 Gy +/- 14.01 (range 1.9-39) and 1.75 Gy +/- 9.72 (range 0.8-29), respectively. CONCLUSION: The standard tangential fields do not entirely include Levels I and II axillary nodes.     

First results of a phase I/II dose escalation trial in non-small cell lung cancer using three-dimensional conformal radiotherapy.

PURPOSE: To evaluate the feasibility of dose escalation in non-small cell lung cancer (NSCLC) using three-dimensional conformal radiation therapy. PATIENTS AND METHODS: The main eligibility criteria of the trial were: pathologically proven inoperable NSCLC, ECOG performance status or=grade 3 (SWOG), grade 3 early and grade 2 late esophageal toxicity or any other (RTOG) grade 3 or 4 complications). RESULTS: Fifty-five patients were included. Tumor stage was I/II in 47%, IIIA in 33% and IIIB in 20%. The majority of the patients received a dose of 74.3 Gy (n=17) or 81.0 Gy (n=23). Radiation pneumonitis occurred in seven patients: four patients developed a grade 2, two patients grade 3 and one patient a grade 4. Esophageal toxicity was mild. In 50 patients tumor response at 3 months follow-up was evaluable. In six patients a complete response was recorded, in 38 a partial response, five patients had stable disease and one patient experienced progressive disease. Only one patient developed an isolated failure in an uninvolved nodal area. So far the radiation dose was safely escalated to 87.8 Gy in group 1 (lowest rMLD), 81.0 Gy in groups 2 and 3 and 74.3 Gy in group 4. CONCLUSION: Three-dimensional conformal radiotherapy enables significant dose escalation in NSCLC. The maximum tolerable dose has not yet been reached in any risk group.     

Safety of adjunctive transvaginal beam therapy in the treatment of squamous cell carcinoma of the uterine cervix

At The University of Texas M. D. Anderson Hospital and Tumor Institute at Houston between 1970 and 1980, 159 patients with bulky cervical cancers of FIGO Stages IB or II were treated with transvaginal orthovoltage radiotherapy (TVR) as an adjunct to standard external beam megavoltage irradiation and brachytherapy. The majority received 10 or 15 Gy air dose in 2-3 fractions using 125-250 kVp X rays. The dose from TVR was ignored in subsequent standard treatment planning. The absolute 5-year local control and survival rates were 82 and 83%, respectively. A total of 9 patients (5.7%) developed serious treatment complications that were significantly related to performance of a staging lymphadenectomy prior to radiotherapy and to an external beam pelvic dose of 50 +/- 0.5 Gy versus 40 +/- 0.5 Gy. The risk complications was not related to the dose of TVR or brachytherapy within the ranges used. Provided patients are properly selected and appropriate technical precautions are exercised, TVR is a safe technique. It is effective in controlling bleeding and shrinking large exophytic tumors, and very likely contributes to improved tumor control by facilitating optimal geometry for intracavitary therapy.     

Results of combined therapy for malignant tumors of the nasal cavity and accessory nasal sinus depending on the fractionation of preoperative radiotherapy

Data on the treatment of 215 patients with locally advanced malignancies of the nasal cavity and accessory nasal sinus are presented. All patients received preoperative radiotherapy using different fractionation schemes under a total target dose (TTD) of 32-40 Gy. Surgery was carried out two weeks later. Whenever radicality of surgery was in doubt, postoperative gamma therapy included exposure to 2 Gy 5 times a week (TTD--30-40 Gy) (n=121). Group I (n-57) received radiation at standard fractionated dosage. In group II (n=66), fractionation, tentatively considered "dynamic" was used while, in group III, fractionation was dynamic in actual fact. In group IV (n=10), superfractionation (1+1 Gy) was employed in group V (n=6),--gamma-neutron therapy. Patients in group VI (n=51) were operated on as scheduled and received 5 Gy, twice a week (TTD--20 Gy). According to 5-year follow-up, the best results were obtained with the use of larger doses of preoperative radiation (groups II, III, VI). Postoperative radiotherapy proved ineffective and it would be useless unless ablative procedures were definitely faulty during surgery.     

In-vivo dosimetry by diode semiconductors in combination with portal films during TBI: reporting a 5-year clinical experience.

BACKGROUND AND PURPOSE: In-vivo dosimetry is vital to assure an accurate delivery of total body irradiation (TBI). In-vivo lung dosimetry is strongly recommended because of the risk of radiation-induced interstitial pneumonia (IP). Here we report on our 5-year experience with in-vivo dosimetry using diodes in combination with portal films and assessing the effectiveness of in-vivo dosimetry in improving the accuracy of the treatment. Moreover, we wished to investigate in detail the possibility of in-vivo portal dosimetry to yield individual information on the lung dose and to evaluate the impact of CT planning on the correspondence between stated and in-vivo measured doses. MATERIALS AND METHODS: From March 1994 to March 1999, 229 supine-positioned patients were treated at our Institute with TBI, using a 6 MV X-rays opposed lateral beam technique. 146 patients received 10 Gy given in three fractions, once a day (FTBI), shielding the lungs by the arms; 70 received 12-13.2 Gy, given in 6-11 fractions, 2-3 fractions per day (HFTBI): in this case about 2/3 of the lungs were shielded by moulded blocks (mean shielded lung dose equal to 9 or 9.5 Gy). Thirteen patients received 8 Gy given in a single fraction (SFTBI, lung dose: 7 Gy). For all HFTBI and FTBI patients, midline in-vivo dosimetry was performed at the first fraction by positioning two diodes pairs (one at entrance and one at the exit side) at the waist (umbilicus) and at the pelvis (ankles). If at least one of the two diodes doses (waist-pelvis) was outside +/-5% from the prescribed dose, actions could be initiated, together with possible checks on the following fractions. Transit dosimetry by portal films was performed for most patients; for 165 of them (117 and 48, respectively for FTBI and HFTBI) the midline in-vivo dose distribution of the chest region was derived and mean lung dose assessed. As a CT plan was performed for all HFTBI patients, for these patients, the lung dose measured by portal in-vivo dosimetry was compared with the expected value. RESULTS: Concerning all diodes data, 528 measurements were available: when excluding the data of the first fraction(s) of the patients undergoing corrections (n = 392), mean and SD were respectively 0.0% and 4.5% (FTBI: -0.3 +/- 4.8%; HFTBI: 0.4 +/- 3.9%). In total 105/229 patients had a change after the first fraction and 66/229 were controlled by in-vivo dosimetry for more than one fraction. Since January 1998 a CT plan is performed for FTBI patients too: when comparing the diodes data before and after this date, a significant improvement was found (i.e. rate of deviations larger than 5% respectively equal to 30.7% and 13.1%, P = 0.007). When considering only the patients with a CT plan, the global SD reduced to 3.5%. Concerning transit dosimetry data, for FTBI, the mean (midline) lung dose was found to vary significantly from patient to patient (Average 9.13 +/- 0.81 Gy; range 7.4-11.4 Gy); for the HFTBI patients the mean deviation between measured and expected lung dose was 0.0% (1 SD = 3.8%). CONCLUSIONS: In vivo dosimetry is an effective tool to improve the accuracy of TBI. The impact of CT planning for FTBI significantly improved the accuracy of the treatment delivery. Transit dosimetry data revealed a significant inter-patient variation of the mean lung dose among patients undergoing the same irradiation technique. For patients with partial lung shielding (HFTBI), an excellent agreement between measured and expected lung dose was verified.     

Fractionated stereotactic radiotherapy for acoustic neuromas

PURPOSE: When compared with radiosurgery, fractionated stereotactic radiotherapy for acoustic neuroma (AN) offers escalation of the tumor dose and potential sparing of auditory and facial nerve functions. METHODS AND MATERIALS: Between 1996 and 2001, 249 consecutive patients have received fractionated stereotactic radiotherapy for AN. One hundred twenty-five patients had follow-up >1 year and were the subject of this report. A noninvasive, repeat-fixation mask allowed simulation by way of spiral CT. Two distinct schedules for total dose and fractionation were used. For an AN <3.0 cm in diameter (volume 1.4 +/- 0.2 cm(3)), patients received 25 Gy given in 5 consecutive daily fractions of 5 Gy (111 patients), and for ANs >or=3.0 cm (volume 8.1 +/- 1.2 cm(3)), patients received 30 Gy given in 10 fractions of 3 Gy (14 patients). RESULTS: The percentage of decrease in tumor size was 12% +/- 2% (range 0-100%) vs. 13% +/- 3% (range 0-38%) for the 25 Gy vs. 30 Gy regimens, respectively. No patient had growth of the AN or developed facial weakness. Two patients developed transient decreases in facial sensation. The rates of hearing preservation were similar for the larger and smaller tumors. CONCLUSION: Fractionated stereotactic radiotherapy may preserve normal function and control both small and large ANs.     

MRI-guided 3D optimization significantly improves DVH parameters of pulsed-dose-rate brachytherapy in locally advanced cervical cancer

PURPOSE: To compare dose-volume histogram parameters of standard Point A and magnetic resonance imaging-based three-dimensional optimized dose plans in 21 consecutive patients who underwent pulsed-dose-rate brachytherapy (PDR-BT) for locally advanced cervical cancer. METHODS AND MATERIALS: All patients received external beam radiotherapy (elective target dose, 45 Gy in 25-30 fractions; tumor target dose, 50-60 Gy in 25-30 fractions). PDR-BT was applied with a tandem-ring applicator. Additional ring-guided titanium needles were used in 4 patients and a multichannel vaginal cylinder in 2 patients. Dose planning was done using 1.5 Tesla T(1)-weighted and T(2)-weighted paratransversal magnetic resonance imaging scans. T(1)-weighted visible oil-containing tubes were used for applicator reconstruction. The prescribed standard dose for PDR-BT was 10 Gy (1 Gy/pulse, 1 pulse/h) for two to three fractions to reach a physical dose of 80 Gy to Point A. The total dose (external beam radiotherapy plus brachytherapy) was normalized to an equivalent dose in 2-Gy fractions using alpha/beta = 10 Gy for tumor, alpha/beta = 3 Gy for normal tissue, and a repair half-time of 1.5 h. The goal of optimization was dose received by 90% of the target volume (D(90)) of > or =85 Gy(alpha/beta10) in the high-risk clinical target volume (cervix and remaining tumor at brachytherapy), but keeping the minimal dose to 2 cm(3) of the bladder and rectum/sigmoid at <90 and <75 Gy(alpha/beta3), respectively. RESULTS: Using three-dimensional optimization, all dose-volume histogram constraints were met in 16 of 21 patients compared with 3 of 21 patients with two-dimensional library plans (p < 0.001). Optimization increased the minimal target dose (D(100)) of the high-risk clinical target volume (p < 0.007) and decreased the minimal dose to 2 cm(3) for the sigmoid significantly (p = 0.03). For the high-risk clinical target volume, D(90) was 91 +/- 8 Gy(alpha/beta10) and D(100) was 76 +/- 5 Gy(alpha/beta10). The minimal dose to 2 cm(3) for the bladder, rectum, and sigmoid was 73 +/- 6, 67 +/- 6, and 69 +/- 6 Gy(alpha/beta3), respectively. CONCLUSION: The results of our study have shown that magnetic resonance imaging-guided optimization of PDR-BT for locally advanced cervical cancer significantly improved the dose-volume histogram parameters.     

Analysis of the Survival Rate with Cervical Cancer Using ^137Cs and ^192Ir Aftedoading Brachytherapy

Objective To analyze and compare the survival rate for stages II and III cervical cancer treated by external irradiation plus¹³⁷Cs or¹⁹²lr. Methods The patients with cervical cancer were treated by external irradiation plus¹³⁷Cs (group A, 427 patients) or plus¹⁹²lr (group B, 156 patients). There were 170 stage II cases and 413 stage III cases. The number of cancer types were as follows: squamous cell carcinoma, 524; adenocarcinoma, 34; and adenosquamous cell carcinoma, 25. The two groups received the same external irradiation using 8 or 10 MV of X-ray. After the whole pelvis received 25–35 Gy, the focus was given a total of 45–55 Gy by four divided fields. Intracavitary irradiation was performed with one fraction of 6–7 Gy in reference dose at A point every week and a total dose of 40 -60 Gy with 6 ~8 fractions for group A; every fraction of 5 -6 Gy in reference dose of A point and total dose of 30–42 Gy with 5~7 fractions for group B. Results The 5-year survival rate of stage II and III, and total were 82.9%, 62.2%, and 67.2% for group A respectively and 85.1%, 61.5% and 69.2% for group B respectively. There were significant differences between stage II and III in each group (P< 0.05) but there were no differences in the 5-year survival rate between the two groups (P> 0.05). The late complications of the therapy were rectitis and urocystitis and with an incidence rate of 7.3% and 6.3% for group A and 9.6% and 9.0% for group B (P> 0.05). Conclusion The long-term survival rate and complications of stages II and III cervical cancer are similar when treated with external irradiation plus¹³⁷Cs or plus¹⁹²lr.     

Final results of a Phase I/II dose escalation trial in non-small-cell lung cancer using three-dimensional conformal radiotherapy

PURPOSE: The aim of this study was to determine the maximum tolerated dose (MTD) delivered within 6 weeks in patients with non-small-cell lung cancer (NSCLC). The impact of tumor volume and delivered dose on failure-free interval (FFI) and overall survival (OS) were also studied. METHODS AND MATERIALS: A Phase I/II trial was performed including inoperable NSCLC patients. According to the relative mean lung dose (rMLD), five risk groups with different starting doses were defined: Group 1, rMLD 0.0 to 0.12; Group 2, rMLD 0.12 to 0.18; Group 3, rMLD 0.18 to 0.24; Group 4, rMLD 0.24 to 0.31; and Group 5, rMLD 0.31 to 0.40. Patients underwent irradiation with 2.25 Gy per fraction and a fixed overall treatment time of 6 weeks. The dose was escalated with 6.75 Gy after 6 months follow-up without dose-limiting toxicity. If more than 30 fractions were prescribed, twice-daily irradiation was performed with at least a 6-h interval. RESULTS: A total of 88 patients were included. Tumor Stage I or II was found in 53%, IIIA in 31%, and IIIB in 17%. The MTD was not achieved in risk Group 1 (reached dose, 94.5 Gy). For risk Groups 2 and 3 the MTD was 81 Gy. The 74.3-Gy dose was determined to be safe for Group 4 and the 60.8-Gy dose for Group 5. In 2 patients (5%) an isolated nodal relapse occurred. Based on multivariable analysis, higher doses significantly increased the FFI (p = 0.02) for the total group. The OS was increased in the lower risk groups (p = 0.05) but not in the higher risk groups (p = 0.4). CONCLUSION: Dose escalation is safe up to 94.5 Gy in 42 fractions in 6 weeks in patients with an MLD 13.6 Gy or less. Higher doses are associated with a better FFI and OS for smaller tumor volumes. Involved-field irradiation results in a low percentage of isolated nodal relapses.     

Randomized Pilot Study of 20 Gy in 5 Fractions versus 27 Gy in 3 Fractions Radiotherapy for Treating Painful Bone Metastases: A Single Institution Experience

Purpose: Radiotherapy is a very effective tool in the treatment of painful bone metastases. The aim of this study was to compare the palliative effect of radiotherapy between the standard fractionation schedule 20 Gy over 5 fractions (20Gy/5fr) and the high biological dose schedule 27 Gy over 3 fractions (27Gy/3fr) which is frequently used in Stereotactic body radio-surgery (SBRT). Methods: Patients were randomized to receive (20Gy/5fr)or (27Gy/3fr). The primary aim of the study was pain relief using the numeric rating scale (NRS), after three months of radiation therapy. Secondary end points include pain relief immediately after finishing radiation therapy (within one week), and narcotic relief after three months of radiation therapy. Results: Twenty-two patients with painful bone metastases were included. 12 patients received (20Gy/5fr) and 10 patients received (27Gy/3fr). Male patients were predominant on both arms (81.8%) with a mean age of 58 years [ranging between 19-72 years]. For pain relief after three months of radiation therapy, partial pain relief was documented in 9 patients (75%) with (20Gy/5fr) and in 8 patients (80%) with (27Gy/3fr) with a p- value of 0.6. Additionally, narcotic relief after three months was equal for both groups. For immediate pain relief, partial pain relief was seen in one patient (8%) with (20Gy/5fr) versus seven patients (70%) with (27Gy/3fr) with a p value of 0.06. The increase in immediate pain relief in the 27Gy arm was numerically but not statistically significant. Conclusion: SBRT and standard fractionation radiation therapy had equal effectiveness for pain relief, when the assessment was done after three months of radiation therapy. Interestingly, SBRT had a better immediate pain relief.     

食管癌后程加速超分割照射剂量学研究

目的探讨食管癌后程加速超分割照射剂量并观察两组的近期疗效、局部控制率、放疗耐受性及副反应，并随访其长期生存率。方法采用随机抽签法将100例食管癌随机均分为60Gy组和75Gy组。60Gy组前3周采用常规分割照射，第4周起改用超分割照射（1．5Gy／次，2次／d，2次间隔6h，10次／周），DT60Gy分35次，5周完成。75Gy组照射方法完全相同，前3周常规分割，第4周起改用超分割照射，DT75Gy，分45次，6周完成。结果两组近期疗效无差别，75Gy组无C级。1、3、5年局部控制率60Gy组分别为86％、42％、32％，75Gy组分别为88％、52％、48％；1、3、5年生存率60Gy组分别为86％、40％、28％，75Gy组分别为72％、34％、16％；两组比较均无差别。中位生存期60Gy组25个月，75Gy组19个月。75Gy组重度放射性食管炎明显高于60Gy组（28％：10％，P=0．022），但75Gy组与60Gy组死亡原因无差别。结论食管癌后程加速超分割照射不宜追求高剂量，在照射野及照射技术不变的情况下增加剂量，副反应加大。在考虑增加照射剂量时应充分考虑肺及其他正常组织的量照体积及受照剂苗。