Results of carbon ion radiotherapy in 152 patients

PURPOSE: This study summarizes the experience with raster scanned carbon ion radiation therapy (RT) at the Gesellschaft für Schwerionenforschung (GSI), Darmstadt, Germany since 1997. METHODS AND MATERIALS: Between December 1997 and December 2002, 152 patients were treated at GSI with carbon ion RT. Eighty-seven patients with chordomas and low-grade chondrosarcomas of the skull base received carbon ion RT alone (median dose 60 GyE); 21 patients with unfavorable adenoid cystic carcinomas and 17 patients with spinal (n = 9) and sacrococcygeal (n = 8) chordomas and chondrosarcomas were treated with combined photon and carbon ion RT. Twelve patients received reirradiation with carbon ions with or without photon RT for recurrent tumors. Furthermore, 15 patients with skull base tumors other than chordoma and low-grade chondrosarcoma were treated with carbon ions. RESULTS: Actuarial 3-year local control was 81% for chordomas, 100% for chondrosarcomas, and 62% for adenoid cystic carcinomas. Local control was obtained in 15/17 patients with spinal (8/9) and sacral (7/8) chordomas or chondrosarcomas and in 11/15 patients with skull base tumors other than chordomas and low-grade chondrosarcomas, respectively. Six of 12 patients who received reirradiation are still alive without signs of tumor progression. Common Toxicity Criteria Grade 4 or Grade 5 toxicity was not observed. CONCLUSION: Carbon ion therapy is safe with respect to toxicity and offers high local control rates for skull base tumors such as chordomas, low-grade chondrosarcomas, and unfavorable adenoid cystic carcinomas.     

Acute radiation-induced toxicity of heavy ion radiotherapy delivered with intensity modulated pencil beam scanning in patients with base of skull tumors.

PURPOSE: The purpose of this paper is to evaluate acute radiation-induced toxicity of carbon ion therapy. MATERIAL AND METHODS: From December 1997 to November 2000, 37 patients with chordomas and low-grade chondrosarcomas of the skull base have been treated with carbon ions at the heavy ion synchrotron (SIS) at GSI, Darmstadt. Tumor-conformal application of carbon beams was realized by intensity-controlled raster scanning in combination with pulse-to-pulse energy variation. The treatment planning procedure included a biological plan optimization. We applied a cobalt-Gray equivalent dose of 60GyE. Acute toxicity was assessed according to the common toxicity criteria (CTC). RESULTS: Acute toxicity included skin reactions ( degrees I+ degrees II) in four patients, mucositis ( degrees I- degrees III) in eight patients, otitis and middle ear effusion in four, sinusitis in four, nausea/weight loss in one and edema of the temporal lobes in one patient. In two patients, preexisting neurological symptoms worsened. We did not observe acute morbidity > degrees III of normal tissues. CONCLUSION: Scanning beam delivery of heavy charged particles is safe and reliable. No unexpected acute dose limiting toxicity was observed. With regard to toxicity, a substantial improvement compared to passive beam shaping technology is achieved.     

Results of spot-scanning proton radiation therapy for chordoma and chondrosarcoma of the skull base: the Paul Scherrer Institut experience

PURPOSE: To assess the clinical results of spot scanning proton beam radiation therapy (PT) in the treatment of skull base chordomas and low-grade chondrosarcomas (CS). METHODS AND MATERIALS: Between October 1998 and October 2003, 29 patients (median age, 39 years) with chordomas (n = 18) and CS (n = 11) were treated at the Paul Scherrer Institut (PSI) with protons using the main 510-MeV cyclotron. Tumor conformal application of proton beams was realized by spot scanning technology. The median chordoma and CS dose was 74 and 68 cobalt Gy equivalent, respectively (cobalt Gy equivalent = proton Gy x 1.1). Median gross tumor volumes (GTV) were 16.4 mL (range, 1.8-48.1 mL) and 15.2 mL (range, 2.3-57.3 mL) for chordoma and CS, respectively. Late toxicity was assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE, v3.0) grading system. The median follow-up time was 29 months (range, 6-68 months). RESULTS: Actuarial 3-year local control rates were 87.5% and 100% for chordoma and CS, respectively. We observed one surgical pathway and one marginal failure in patients with chordomas. No regional failure or distant metastasis was observed. At 3 years, actuarial PFS and OS for the entire cohort was 90% and 93.8%, respectively. Actuarial 3-year complication-free survival was 82.2%. Radiation-induced pituitary dysfunction was observed in 4 (14%) patients (CTCAE Grade 2). No patient presented with post-PT brainstem or optic pathways necrosis or dysfunction. In univariate analysis, age < or =40 years at the time of PT affected favorably on PFS (p = 0.09). CONCLUSION: Spot-scanning PT offers high tumor control rates of skull base chordoma and CS. These results compare favorably to other combined proton-photon or carbon ion irradiation series. Observed toxicity was acceptable. Younger age (< or =40 years) was a favorable prognostic factor of PFS. These preliminary results are encouraging but should be confirmed during a longer follow-up.     

Stereotactic fractionated radiotherapy for chordomas and chondrosarcomas of the skull base

PURPOSE: To investigate the treatment outcome of patients suffering from skull base chordoma or chondrosarcoma after fractionated stereotactic radiotherapy. METHODS AND MATERIALS: We report 45 patients treated for chordoma or chondrosarcoma with postoperative fractionated stereotactic radiotherapy between 1990 and 1997. Patients had CT and MRI for 3D treatment planning performed under stereotactic guidance. Median dose at isocenter was 66.6 Gy for chordomas and 64.9 Gy for chondrosarcomas. MRI imaging was obtained in intervals after therapy to evaluate local relapse. Survival was calculated according to the Kaplan-Meier method. RESULTS: All chondrosarcomas had achieved and maintained local control and recurrence-free status at follow-up of 5 years. Local control rate of chordomas was 82% at 2 years and 50% at 5 years. Survival was 97% at 2 years and 82% at 5 years. At maximum follow-up of 8 years local control and survival rate of chordomas was 40% (82%). Clinically significant late toxicity developed in one patient. CONCLUSIONS: Our results demonstrate the feasibility of fractionated photon beam therapy and its success in the treatment of skull base tumors. Modern 3D treatment techniques provide superior results compared to conventional techniques. The role of high-precision radiotherapy compared to particle beam therapy in the treatment of these tumors is not yet fully clear and further research is needed.     

Carbon ion radiotherapy of skull base chondrosarcomas

PURPOSE: To evaluate the effectiveness and toxicity of carbon ion radiotherapy in chondrosarcomas of the skull base. PATIENTS AND METHODS: Between November 1998 and September 2005, 54 patients with low-grade and intermediate-grade chondrosarcomas of the skull base have been treated with carbon ion radiation therapy (RT) using the raster scan technique at the Gesellschaft für Schwerionenforschung in Darmstadt, Germany. All patients had gross residual tumors after surgery. Median total dose was 60 CGE (weekly fractionation 7 x 3.0 CGE). All patients were followed prospectively in regular intervals after treatment. Local control and overall survival rates were calculated using the Kaplan-Meier method. Toxicity was assessed according to the Common Terminology Criteria (CTCAE v.3.0) and the Radiation Therapy Oncology Group (RTOG)/European Organization for Research and Treatment of Cancer (EORTC) score. RESULTS: Median follow-up was 33 months (range, 3-84 months). Only 2 patients developed local recurrences. The actuarial local control rates were 96.2% and 89.8% at 3 and 4 years; overall survival was 98.2%at 5 years. Only 1 patient developed a mucositis CTCAE Grade 3; the remaining patients did not develop any acute toxicities >CTCAE Grade 2. Five patients developed minor late toxicities (RTOG/EORTC Grades 1-2), including bilateral cataract (n = 1), sensory hearing loss (n = 1), a reduction of growth hormone (n = 1), and asymptomatic radiation-induced white matter changes of the adjacent temporal lobe (n = 2). Grade 3 late toxicity occurred in 1 patient (1.9%) only. CONCLUSIONS: Carbon ion RT is an effective treatment for low- and intermediate-grade chondrosarcomas of the skull base offering high local control rates with low toxicity.     

Outcomes of visual acuity in carbon ion radiotherapy: analysis of dose-volume histograms and prognostic factors

PURPOSE: To analyze the tolerance dose for retention of visual acuity in patients with head-and-neck tumors treated with carbon ion radiotherapy. METHODS AND MATERIALS: From June 1994 to March 2000, 163 patients with tumors in the head and neck or skull base region were treated with carbon ion radiotherapy. Analysis was performed on 54 optic nerves (ONs) corresponding to 30 patients whose ONs had been included in the irradiated volume. These patients showed no evidence of visual impairment due to other factors and had a follow-up period of >4 years. All patients had been informed of the possibility of visual impairment before treatment. We evaluated the dose-complication probability and the prognostic factors for the retention of visual acuity in carbon ion radiotherapy, using dose-volume histograms and multivariate analysis. RESULTS: The median age of 30 patients (14 men, 16 women) was 57.2 years. Median prescribed total dose was 56.0 gray equivalents (GyE) at 3.0-4.0 GyE per fraction per day (range, 48-64 GyE; 16-18 fractions; 4-6 weeks). Of 54 ONs that were analyzed, 35 had been irradiated with <57 GyE (maximum dose [Dmax]) resulting in no visual loss. Conversely, 11 of the 19 ONs (58%) irradiated with >57 GyE (Dmax) suffered a decrease of visual acuity. In all of these cases, the ONs had been involved in the tumor before carbon ion radiotherapy. In the multivariate analysis, a dose of 20% of the volume of the ON (D20) was significantly associated with visual loss. CONCLUSIONS: The occurrence of visual loss seems to be correlated with a delivery of >60 GyE to 20% of the volume of the ON.     

Carbon ion radiotherapy for unresectable sacral chordomas.

PURPOSE: The purpose is to evaluate the efficacy and toxicity of carbon ion radiotherapy for unresectable sacral chordomas. EXPERIMENTAL DESIGN: We performed a retrospective analysis of 30 patients with unresectable sacral chordomas treated with carbon ion radiotherapy at the Heavy Ion Medical Accelerator in Chiba, Japan. Twenty-three patients presented with no prior treatment, and the remaining 7 patients had locally recurrent disease following previous surgical resection. The median clinical target volume was 546 cm(3). The applied carbon ion dose ranged from 52.8 to 73.6 GyE (gray equivalent, median 70.4) in 16 fixed fractions over 4 weeks. RESULTS: At median follow-up of 30 months (range, 9 to 87 months), 26 patients were still alive and 24 patients remained continuously disease-free. Overall and cause-specific survival rates at 5 years were 52 and 94%, respectively. The overall local control rate at 5 years was 96%. Two patients experienced severe skin/soft tissue complications requiring skin grafts. No other treatment-related surgical interventions, including colostomy or urinary diversion, were carried out. All patients have remained ambulatory and able to stay at home after carbon ion radiotherapy. CONCLUSIONS: Carbon ion radiotherapy is effective and safe in the management of patients with unresectable sacral chordomas and offers a promising alternative to surgery.     

Combination of photon and proton radiation therapy for chordomas and chondrosarcomas of the skull base: the Centre de Protonthérapie D'Orsay experience

PURPOSE: Prospective analysis of local tumor control, survival, and treatment complications in 44 consecutive patients treated with fractionated photon and proton radiation for a chordoma or chondrosarcoma of the skull base. METHODS AND MATERIALS : Between December 1995 and December 1998, 45 patients with a median age of 55 years (14-85) were treated using a 201-MeV proton beam at the Centre de Protonthérapie d'Orsay, 34 for a chordoma and 11 for a chondrosarcoma. Irradiation combined high-energy photons and protons. Photons represented two-thirds of the total dose and protons one-third. The median total dose delivered within the gross tumor volume was 67 cobalt Gray equivalent (CGE) (range: 60-70). RESULTS: With a mean follow-up of 30.5 months (range: 2-56), the 3-year local control rates for chordomas and chondrosarcomas were 83.1% and 90%, respectively, and 3-year overall survival rates were 91% and 90%, respectively. Eight patients (18%) failed locally (7 within the clinical tumor volume and 1 unknown). Four patients died of tumor and 2 others of intercurrent disease. In univariate analysis, young age at time of radiotherapy influenced local control positively (p < 0.03), but not in multivariate analysis. Only 2 patients presented Grade 3 or 4 complications. CONCLUSION: In skull-base chordomas and chondrosarcomas, the combination of photons with a proton boost of one-third the total dose offers an excellent chance of cure at the price of an acceptable toxicity. These results should be confirmed with a longer follow-up.     

Radiation therapy for chordomas and chondrosarcomas of the base of the skull and cervical spine

PURPOSE: Prospective analysis of local tumour control, survival and treatment complications in 67 consecutive patients treated with fractionated photon and proton radiation for a chordoma or a chondrosarcoma of the base of the skull and of the cervical spine. PATIENTS AND METHODS: Between December 1995 and January 2000, 67 patients with a median age of 52.3 years (14-85), were treated using 201 MeV proton beam of the centre de protonthérapie d'Orsay (CPO), 49 for a chordoma and 18 for a chondrosarcoma. Irradiation combined high-energy photons and protons. Photons represented 2/3 of the total dose and protons 1/3. The median total dose delivered within gross tumour volume was 67 Cobalt Gray Equivalent (CGE) (60-70). RESULTS: With a mean follow-up of 32 months (4-71), the 3-year local control rates were for chordomas and chondrosarcomas of 70.8% and 85.2%, respectively and 4-year overall survival rates of 87.7% and 75%, respectively. Fourteen tumours (21.5%) failed locally (eight within the gross tumor volume, four into the CTV and 2 in an unknown site). Seven patients died of tumour and one of intercurrent disease. In univariate analysis, age inférieur ou égal à 52.3 years (p = 0.002), maximum tumoral diameter < 44.7 mm (p = 0.02) and GTV < 28.4 mL (0.02), at time of radiotherapy, influenced positively the local control. According to multivariate analysis, only age was an independent prognostic factor of local control. Only five (7.7%) patients presented grade 3 or 4 complications. CONCLUSION: In base of skull chordomas and chondrosarcomas, the combined photon and proton therapy offers excellent chances of cure at the price of an acceptable toxicity. These results should be confirmed with a longer follow-up.     

Proton therapy in pediatric skull base and cervical canal low-grade bone malignancies

PURPOSE: To evaluate outcomes and tolerance of high-dose photon and proton therapy in the management of skull base and cervical canal primary bony malignancies in children. PATIENTS AND METHODS: Thirty children were treated postoperatively with high-dose photon-proton (29 patients) or protons-only (1 patient) radiotherapy. Twenty-six patients had chordomas (CH), 3 had low-grade chondrosarcomas (CS), and 1 had an aggressive chondroma (AC). The mean age was 12.8 years. At the time of radiation, all but 1 patient had a gross residue. The anatomic sites affected were skull base (n = 16), cervical canal (n = 1), or both (n = 13). Mean total dose was 68.4 cobalt Gray equivalents, conventionally fractionated. RESULTS: With a mean follow-up of 26.5 months, 5 of 30 children failed locally: 5 of 5 lesions were CH, 5 of 5 patients had experienced pain at presentation (p = 0.03), and 4 of 5 had cervical extension (p = 0.07). The 5-year overall survival/progression-free survival rates for CS and CH were 100%/100% and 81%/77%, respectively. Side effects were scored according to the National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. Acute toxicity ranged between 0 and 2. Late toxicity of radiotherapy was severe in 1 patient (Grade 3 auditory) and minor or mild in the rest of the population (7 patients with Grade 2 pituitary dysfunction). CONCLUSIONS: High-dose combined fractionated photon-proton therapy is well tolerated in children and allows excellent local control with minimal long-term toxicity.     

Efficacy and safety of carbon ion radiotherapy in bone and soft tissue sarcomas.

PURPOSE: To evaluate the tolerance for and effectiveness of carbon ion radiotherapy in patients with unresectable bone and soft tissue sarcomas. PATIENTS AND METHODS: We conducted a phase I/II dose escalation study of carbon ion radiotherapy. Fifty-seven patients with 64 sites of bone and soft tissue sarcomas not suited for resection received carbon ion radiotherapy. Tumors involved the spine or paraspinous soft tissues in 19 patients, pelvis in 32 patients, and extremities in six patients. The total dose ranged from 52.8 to 73.6 gray equivalent (GyE) and was administered in 16 fixed fractions over 4 weeks (3.3 to 4.6 GyE/fraction). The median tumor size was 559 cm(3) (range, 20 to 2,290 cm(3)). The minimum follow-up was 18 months. RESULTS: Seven of 17 patients treated with the highest total dose of 73.6 GyE experienced Radiation Therapy Oncology Group grade 3 acute skin reactions. Dose escalation was then halted at this level. No other severe acute reactions (grade > 3) were observed in this series. The overall local control rates were 88% and 73% at 1 year and 3 years of follow-up, respectively. The median survival time was 31 months (range, 2 to 60 months), and the 1- and 3-year overall survival rates were 82% and 46%, respectively. CONCLUSION: Carbon ion radiotherapy seems to be a safe and effective modality in the management of bone and soft tissue sarcomas not eligible for surgical resection, providing good local control and offering a survival advantage without unacceptable morbidity.     

Dose escalation study of carbon ion radiotherapy for locally advanced carcinoma of the uterine cervix

PURPOSE: To evaluate the toxicity and efficacy of carbon ion radiotherapy (CIRT) for locally advanced cervical cancer by two phase I/II clinical trials. METHODS AND MATERIALS: Between June 1995 and January 2000, 44 patients were treated with CIRT. Thirty patients had Stage IIIB disease, and 14 patients had Stage IVA disease. Median tumor size was 6.5 cm (range, 4.2-11.0 cm). The treatment consisted of 16 fractions of whole pelvic irradiation and 8 fractions of local boost. In the first study, the total dose ranged from 52.8 to 72.0 gray equivalents (GyE) (2.2-3.0 GyE per fraction). In the second study, the whole pelvic dose was fixed at 44.8 GyE, and an additional 24.0 or 28.0 GyE was given to the cervical tumor (total dose, 68.8 or 72.8 GyE). RESULTS: No patient developed severe acute toxicity. In contrast, 8 patients developed major late gastrointestinal complications. The doses resulting in major complications were > or =60 GyE. All patients with major complications were surgically salvaged. The 5-year local control rate for patients in the first and second studies was 45% and 79%, respectively. When treated with > or =62.4 GyE, the local control was favorable even for the patients with stage IVA disease (69%) or for those with tumors > or =6.0 cm (64%). CONCLUSIONS: In CIRT for advanced cervical cancer, the dose to the intestines should be limited to <60 GyE to avoid major complications. Although the number of patients in this study was small, the results support continued investigation to confirm therapeutic efficacy.     

Treatment with high marginal dose is mandatory to achieve long-term control of skull base chordomas and chondrosarcomas by means of stereotactic radiosurgery

Chordomas and chondrosarcomas of the skull base are rare. Since total resection of these tumors is difficult, adjuvant radiotherapy is necessary. This study was performed to evaluate the effect of stereotactic radiosurgery (SRS) for skull base chordomas and chondrosarcomas and to determine the optimal marginal dose for these tumors. Fourteen patients with histologically proven chordomas or chondrosarcomas underwent 16 sessions of SRS using gamma knife. The marginal doses ranged from 10 to 20 Gy (mean, 15 Gy). Lower marginal doses of 12 Gy on average (range, 10–12.5 Gy) were applied to four patients since they underwent prior fractionated radiotherapy, and partial treatment for which parts of tumors were excluded from planned target volume because of their proximity to critical structures was also applied to four patients. The whole tumors were covered with higher marginal doses of 18 Gy on average (range, 16–20 Gy) for six patients. The mean follow-up period was 65 months. Progression-free survival (PFS) rates at 3 and 5 years after SRS was 53 and 43%, respectively. Five-year PFS rates for patients who underwent SRS with higher and lower marginal doses were 80 and 14%, respectively, which were significantly different (P = 0.005). Tumor progression after partial irradiation mainly occurred from sites where delivered doses were reduced. Sufficient marginal doses at least 16 Gy appeared crucial. Proper combination with surgical resection to detach tumors from critical structures and to reduce tumor volume is necessary to completely deliver sufficient marginal doses for SRS.     

Feasibility and toxicity of combined photon and carbon ion radiotherapy for locally advanced adenoid cystic carcinomas

PURPOSE: To investigate clinical feasibility and toxicity of combined photon and carbon ion radiotherapy in locally advanced adenoid cystic carcinomas (ACC) within a prospective Phase I/II trial. METHODS AND MATERIALS: Between September 1998 and April 2002, 16 patients with histopathologically proven ACC and residual macroscopic tumor were treated with combined photon RT and a carbon ion boost to the macroscopic tumor. Median total tumor dose within the gross tumor volume (GTV) was 72 GyE. Photon radiation therapy (RT) consisted of fractionated stereotactic RT in 7 patients; 9 patients received stereotactic intensity-modulated RT. Carbon ion boost was delivered by intensity-controlled raster scanning at the heavy ion synchrotron (SIS) at the Heavy Ion Research Center (GSI) in Darmstadt. RESULTS: Median follow-up was 12 months. Three patients developed locoregional recurrences 9, 11, and 24 months after RT, respectively. Actuarial local control rates were 80.8% and 64.6% at 1 and 3 years, respectively. Overall survival rates were 100% and 83.3% at 1 and 3 years, respectively. Acute side effects greater than Common Toxicity Criteria (CTC) Grade 2 were observed in 2 patients; no patient developed late effects > CTC Grade 2. CONCLUSIONS: Combined photon and carbon ion RT is feasible and effective in patients with locally advanced ACC. Acute and late toxicity is moderate with respect to the delivered tumor doses and in accordance with the radiobiologic modeling. A Phase III trial is designed.     

Fractionated proton radiation therapy of cranial and intracranial tumors

Since 1973 fractionated proton radiation therapy has been used in the treatment of malignant disease. Protons have favorable physical characteristics that yield dose distributions superior to those of photons in certain clinical situations. As of December 31, 1987, 1,678 patients had been treated. Of these, 110 had chordomas or low-grade chondrosarcomas of the base of skull. The first 68 patients have a minimum follow-up of 17 months. The median dose was 69 Cobalt Gray Equivalent (CGE). (CGE is the dose in proton Gray multiplied by 1.1, which is the relative biological effectiveness for protons relative to 60Cobalt.) The actuarial 5-year local control rate is 82%, and the disease-free survival rate is 76%. Thirteen patients with meningiomas have been treated, following subtotal resection. The median dose was 59.4 CGE. With a median follow-up of 26 months, no patient has had tumor progression. In addition, nine patients with gliomas and 12 with craniopharyngiomas have been treated.     

Randomised trial of proton vs. carbon ion radiation therapy in patients with low and intermediate grade chondrosarcoma of the skull base,clinical phase III study

Background  

Low and intermediate grade chondrosarcomas are relative rare bone tumours. About 5-12% of all chondrosarcomas are localized in base of skull region. Low grade chondrosarcoma has a low incidence of distant metastasis but is potentially lethal disease. Therefore, local therapy is of crucial importance in the treatment of skull base chondrosarcomas. Surgical resection is the primary treatment standard. Unfortunately the late diagnosis and diagnosis at the extensive stage are common due to the slow and asymptomatic growth of the lesions. Consequently, complete resection is hindered due to close proximity to critical and hence dose limiting organs such as optic nerves, chiasm and brainstem. Adjuvant or additional radiation therapy is very important for the improvement of local control rates in the primary treatment. Proton therapy is the gold standard in the treatment of skull base chondrosarcomas. However, high-LET (linear energy transfer) beams such as carbon ions theoretically offer advantages by enhanced biologic effectiveness in slow-growing tumours.     

Carbon ion radiotherapy for skull base chordomas and chondrosarcomas: a systematic review and meta-analysis of local control,survival, and toxicity outcomes

Journal of Neuro-Oncology - Carbon ion radiotherapy (CIRT) is an emerging radiation therapy to treat skull base chordomas and chondrosarcomas. To date, its use is limited to a few centers around...     

Randomised trial of proton vs. carbon ion radiation therapy in patients with chordoma of the skull base,clinical phase III study HIT-1-Study

Background  

Chordomas of the skull base are relative rare lesions of the bones. Surgical resection is the primary treatment standard, though complete resection is nearly impossible due to close proximity to critical and hence also dose limiting organs for radiation therapy. Level of recurrence after surgery alone is comparatively high, so adjuvant radiation therapy is very important for the improvement of local control rates. Proton therapy is the gold standard in the treatment of skull base chordomas. However, high-LET beams such as carbon ions theoretically offer biologic advantages by enhanced biologic effectiveness in slow-growing tumors.     

Carbon ion radiotherapy for stage I non-small cell lung cancer.

BACKGROUND AND PURPOSE: Heavy ion radiotherapy is a promising modality because of its excellent dose localization and high biological effect on tumors. Using carbon beams, a dose escalation study was conducted for the treatment of stage I non-small cell lung cancer (NSCLC) to determine the optimal dose. MATERIALS AND METHODS: The first stage phase I/II trial using 18 fractions over 6 weeks for 47 patients and the second one using nine fractions over 3 weeks for 34 patients were conducted by the dose escalation method from 59.4 to 95.4 Gray equivalents (GyE) in incremental steps of 10% and from 68.4 to 79.2 GyE in 5% increments, respectively. The local control and survival rates were obtained using the Kaplan-Meier method. RESULTS: Radiation pneumonitis at grade III occurred in three of 81 patients, but they fully recovered. This was not a dose-limiting factor. The local control rates in the first and second trials were 64% and 84%, respectively. The total recurrence rate in both trials was 23.2%. The infield local recurrence in the first trial was significantly dependent on carbon dose. The doses greater than 86.4 GyE at 18 fractions and 72 GyE at nine fractions achieved a local control of 90% and 95%, respectively. The 5 year overall and cause-specific survivals in 81 patients were 42% and 60%, respectively. CONCLUSIONS: With our dose escalation study, the optimum safety and efficacy dose of carbon beams was determined. Carbon beam therapy attained almost the same results as surgery for stage I NSCLC although this was a I/II study.     

Dose escalation study of carbon ion radiotherapy for locally advanced head-and-neck cancer

PURPOSE: To evaluate the toxicity and efficacy of carbon ion radiotherapy for head-and-neck cancer in a Phase I/II dose escalation clinical trial. METHODS AND MATERIALS: Between June 1994 and January 1997, 36 patients with locally advanced, histologically proven, and new or recurrent cancer of the head and neck were treated with carbon ions. A dose escalation study was conducted, delivering 18 fractions through 6 weeks for 17 patients (Group A) and 16 fractions through 4 weeks for 19 patients (Group B). Eligibility and ineligibility criteria were the same in both groups. The dosages were escalated in increments of 10% after careful observation of at least 3 patients treated with the same dosages. The endpoints of the study were a Grade 3 reaction of the skin and the mucous membrane or local control of the tumors. RESULTS: Follow-up time ranged from 77 to 108 months with a median of 90 months. Grade 3 acute reaction of the skin was detected in 1 of the 2 patients in Group A who were treated with 70.2 GyE/18 fractions/6 weeks. In Group B, Grade 3 acute skin reaction was detected in 20% (1/5), 27% (2/11), and 67% (2/3) patients treated with 52.8 GyE, 57.6 GyE, and 64.0 GyE through 16 fractions for 4 weeks, respectively. There was only 1 patient with a Grade 3 acute reaction of the mucous membrane. Only 1 patient developed a Grade 2 late reaction of the mucous membrane (superficial ulcer), which was located close to the tumor. No other Grade 2 or greater late reaction was noted until the time of analysis. Acute tumor reactions in 34 patients consisted of 10 patients of complete response 19 of partial response, 4 of no change, and 1 of progressive disease. Local control of 34 patients calculated by the Kaplan-Meier method was 75% at 5 years. Five years' local control of five malignant melanomas showed 100%, and that of 9 patients with adenoid cystic carcinoma was 90%. Also, local control of 8 patients of salivary glands and 4 patients of ears was 100% at 56 months and 5 years. CONCLUSIONS: The dose fractionation methods of 70.2 GyE through 18 fractions for 6 weeks and 64.0 GyE through 16 fractions for 4 weeks showed equal clinical outcome in terms of morbidity and local control. The outcome of carbon ion radiotherapy showed a specific effectiveness in local control of non-squamous cell carcinoma such as adenoid cystic carcinomas and malignant melanomas. From the results of this study, it can be concluded that carbon ion radiotherapy will deliver a high local control rate without unacceptable injuries to the surrounding normal tissues.