Effektivität und Toxizität einer Re-Bestrahlung (Re-RT) bei metastatisch bedingter Rückenmarkkompression (MBRK)

BACKGROUND AND PURPOSE: Radiation myelopathy is a serious late toxicity after radiotherapy (RT) of metastatic spinal cord compression (MSCC). The risk of myelopathy depends on the equivalent dose in 2-Gy fractions (EQD2). Many radiation oncologists are concerned about spinal Re-RT, because it may result in a high cumulative EQD2. This study investigates effectiveness and feasibility of Re-RT for in-field recurrence of MSCC. PATIENTS AND METHODS: 74 patients, irradiated between 01/1995 and 12/2003 for MSCC, were reirradiated for in-field recurrence of MSCC (Table 1). Primary RT was performed with 1 x 8 Gy (n = 34), 5 x 4 Gy (n = 28), 10 x 3 Gy (n = 4), 15 x 2.5 Gy (n = 4), or 20 x 2 Gy (n = 4). Recurrence occurred after median 6 months (2-40 months). Re-RT was performed with 1 x 8 Gy (n = 35), 5 x 3 Gy (n = 16), 5 x 4 Gy (n = 13), 10 x 2 Gy (n = 4), 12 x 2 Gy (n = 3), or 17 x 1.8 Gy (n = 3). Cumulative EQD2 (alpha/beta = 2 Gy) was 39-40 Gy (n = 21), 49-50 Gy (n = 41), 56-60 Gy (n = 6), or > 60 Gy (n = 6). Follow-up after Re-RT was median 9 months (2-52 months). RESULTS: Re-RT led to an improvement of motor function in 29/74 patients (39%; Figures 1 to 3). On multivariate analysis, outcome was significantly influenced by type of primary tumor (p = 0.013) and by the time of developing motor deficits before Re-RT (p = 0.037), but not by radiation schedule (p = 0.560), by ambulatory status before Re-RT (p = 0.471), by cumulative EQD2 (p = 0.795), nor by the interval between primary RT and Re-RT (p = 0.420; Table 2). Radiation myelopathy was not observed in the whole series. CONCLUSION: Re-RT is an effective treatment for an in-field recurrence of MSCC. After a cumulative EQD2 < or = 50 Gy, radiation myelopathy appears unlikely.     

Gonadenbelastung bei lymphabflußbestrahlung operierter seminome

BACKGROUND: This article should demonstrate the problems concerning gonadal dose in seminoma patients, the impact of shielding and possible consequences for therapy and advising of patients with desire to have children. PATIENTS AND METHOD: Since November 1993 gonadal doses of 43 patients (Stage I/II, Royal Marsden) have been determined in 80 measurements with 2 ionization chambers on the ipsi- and contralateral side of the remaining testicle. The patients were all treated with ap/pa "hockey-stick"-shaped fields on a 6 MV linear accelerator. With single doses of 1.8 Gy in midplane, total doses of 34.2 Gy were applied in 13, and 30.6 Gy in 30 men. Protection was used in 33 patients, 6 times with conventional shielding, later plus an additional clam-shell from ap. The results of 22 measurements on 6 men with and without protection are of special interest. In 25 patients a sperm analysis before radiotherapy was conducted. RESULTS: Before the beginning of radiotherapy (RT) 56% of available patients have shown an impaired spermatogenesis. The mean gonadal doses were 2.4% of midplane dose-MD (4.8 cGy), 1.8% MD (3.2 cGy) and 1% MD (1.8 cGy) per fraction for patients without (n-patients = 10, m-measurements = 15), with conventional (n = 6, m = 7), and additional clam-shell shielding (n = 33, m = 58). The corresponding median values were 2.1% (SD 1.07), 1.7% (SD 0.28) and 1% (SD 0.41) of midplane dose (Table 1, Figure 1). According to direct comparisons, a dose reduction of about half can be expected in most cases (Figure 2). Mean dose fluctuations of 11.6% (median 10%) have to be taken into account. CONCLUSION: Effective shielding can diminish gonadal dose in seminoma patients to about 1% of midplane and gives a good possibility of taking the maintenance of fertility and the desire to have children into account (Table 2). The application should be considered especially for patients with impaired spermatogenesis before RT. Eventual fluctuations induced us to determine the gonadal dose 3 times per patient in direct measurements (Table 3).     

Preliminary toxicity and prostate-specific antigen response of a Phase I/II trial of neoadjuvant hormonal therapy, 103Pd brachytherapy, and three-dimensional conformal external beam irradiation in the treatment of locally advanced prostate cancer

PURPOSE: Standard therapies for locally advanced prostate cancer have resulted in suboptimal disease control rates. A Phase I/II trial was designed for patients with positive seminal vesicle biopsies, prostate-specific antigen (PSA) >15 ng/ml, Gleason score > or =8 or clinical classification T2c-T3 to improve local control and to test the tolerance of the prostate to high-dose radiation by using neoadjuvant hormonal therapy, 103Pd brachytherapy, and conformal three-dimensional external beam radiation therapy (EBRT). This article outlines treatment-related morbidity and PSA response to this regimen and analyzes the effect of escalating doses of brachytherapy. METHODS AND MATERIALS: Forth-three patients with T1c-T3 prostate cancer were enrolled in a Phase I/II trial from March 1994 through September 1997. Follow-up ranged from 12 to 64 months (median, 32 months). Pretreatment PSA ranged from 2.1 to 202 ng/ml (median, 16 ng/ml). Seventy-seven percent (33 of 43) of patients had high-grade tumors (score > or =7). Seventy-four percent (32 of 43) had stage > or =T2c. A total of 21 (49%) patients had positive seminal vesicle biopsies. Treatment consisted of hormonal therapy for 3 months with leuprolide and flutamide followed by a 103Pd implant and, 2 months later, 59.4 Gy of three-dimensional EBRT. Hormonal therapy was continued for 9 months. The planned 103Pd dose was escalated from 57 Gy (13 patients) to 77 Gy (13 patients) to 86 Gy (17 patients). RESULTS: The actuarial freedom from PSA failure (PSA>0.5 ng/ml) at 4 years was 74%. There were no significant differences found when analyzing patients by presenting PSA or seminal vesicle status. There was a trend toward improved outcome with higher doses delivered to the prostate via the implant. Patients receiving doses > or =65 Gy (31 patients) had a freedom from PSA failure rate at 4 years of 89.5%, compared with 52.5% for those receiving doses <65 Gy (10 patients; p=0.08). The last PSA values for those patients free from PSA failure were < or =0.1 ng/ml in 25 (69%), >0.1-0.2 ng/ml in 5 (14%), and >0.2-0.5 ng/ml in 6 (17%). The actuarial freedom from developing Grade 2 proctitis was 75% at 4 years. There was a trend toward increased proctitis with increasing prostate implant doses. Patients with doses < or =70 Gy (n=12) had a 92% freedom from Grade 2 proctitis compared with 67.5% for those with doses delivered to 90% of the gland from a dose-volume histogram of >70 Gy (n=29) (p=0.15). There were no cases of Grade 3 or 4 proctitis. The 3-year actuarial preservation of sexual potency rate was 43%. CONCLUSIONS: The preliminary results from this regimen show an improvement in PSA control for this group of locally advanced prostate cancer patients over more standard therapies. To maximize control while minimizing toxicity, doses of 65-70 Gy of 103Pd should be used when 59.4 Gy of three-dimensional EBRT is delivered. Longer follow-up will be needed to further substantiate these findings.     

Proton Therapy for Head and Neck Malignancies at Tsukuba

PURPOSE: To evaluate the effectiveness and feasibility of proton therapy for head and neck cancers. PATIENTS AND METHODS: From 1983 to 2000, 33 patients with head and neck malignancies but no history of surgical resection were treated with 250-MeV protons with or without X-ray irradiation. This study retrospectively evaluated local control, survival, and treatment sequelae of these patients. The median total target dose using protons with or without X-rays was 76 Gy (range: 42-99 Gy) and the median proton dose per fraction 2.8 Gy (range: 1.5-6.0 Gy). RESULTS: Overall 5-year survival and local control rates were 44% and 74%, respectively. One (3%) and six patients (18%) suffered from treatment-related acute and late toxicity > grade 3 (RTOG/EORTC acute and late radiation morbidity scoring criteria). One patient with a history of radiotherapy suffered from acute toxicity > grade 3. CONCLUSION: Proton therapy appeared to offer high local control rates with few toxicities relative to conventional radiotherapy. However, late toxicity was seen in areas where large radiation doses had been given.     

Outcomes of radiation therapy for maxillary sinus carcinoma

PURPOSE: We evaluated the outcome of radiation therapy for maxillary sinus carcinoma treated in our institution. MATERIALS AND METHODS: From 1984 to 2001, 48 patients with maxillary sinus carcinoma were irradiated with or without chemotherapy and surgery. Patients ranged from 20-89 years of age (median, 68 years) and included 29 men and 19 women. The clinical T factors for these patients, according to the UICC classification (1997), were T2(n = 2), T3(n = 13), and T4(n = 29). Lymph node involvement was observed in 13 patients. The follow-upperiod ranged from 2.5 to 150 months (median, 25 months). The total radiotherapy dose ranged from 40 Gy to 72.8 Gy. Forty-three patients underwent surgery. Intra-arterial chemotherapy was delivered in 39 patients, and systemic chemotherapy was delivered in 7 patients. Fourteen patients were classified as "unresected" (radiation therapy with or without antrostomy), and 34 patients as "resected" (partial, total, or extended total maxillectomy with pre- or postoperativeirradiation). RESULTS: The 5-year overall survival rate(OS), cause-specific survival rate(CSS), and local control rate(LC) of all patients were 52%, 64%, and 75%, respectively. There was no significant difference between the "uaresected" and "resected" groups in OS, CSS, or LC. Local recurrence was observed in 12 patients. In the "resected" group, for local control, it was important to reduce viable tumor before maxillectomy. Preoperative > or = 60 Gy irradiation was considered to be effective to reduce tumor viability. CONCLUSION: There was no significant difference between the "unresected" and "resected" groups in OS, CSS, or LC. In the "resected" group, preoperative irradiation > or = 60 Gy was considered to be effective for local control. In radical treatment of maxillary sinus carcinoma, maxillectomy is not always necessary. Concurrent chemoradiation therapy with or without antrostomy is a reasonable treatment strategy.     

Decreased Local Control Following Radiation Therapy Alone in Early-Stage Glottic Carcinoma with Anterior Commissure Extension*

PURPOSE: To assess the patterns of failure in the treatment of early-stage squamous cell carcinoma of the glottic larynx. PATIENTS AND METHODS: Between 1983-2000, 122 consecutive patients treated for early laryngeal cancer (UICC T1N0 and T2N0) by radical radiation therapy (RT) were retrospectively studied. Male-to-female ratio was 106 : 16, and median age 62 years (35-92 years). There were 68 patients with T1a, 18 with T1b, and 36 with T2 tumors. Diagnosis was made by biopsy in 104 patients, and by laser vaporization or stripping in 18. Treatment planning consisted of three-dimensional (3-D) conformal RT in 49 (40%) patients including nine patients irradiated using arytenoid protection. A median dose of 70 Gy (60-74 Gy) was given (2 Gy/fraction) over a median period of 46 days (21-79 days). Median follow-up period was 85 months. RESULTS: The 5-year overall, cancer-specific, and disease-free survival amounted to 80%, 94%, and 70%, respectively. 5-year local control was 83%. Median time to local recurrence in 19 patients was 13 months (5-58 months). Salvage treatment consisted of surgery in 17 patients (one patient refused salvage and one was inoperable; total laryngectomy in eleven, and partial laryngectomy or cordectomy in six patients). Six patients died because of laryngeal cancer. Univariate analyses revealed that prognostic factors negatively influencing local control were anterior commissure extension, arytenoid protection, and total RT dose < 66 Gy. Among the factors analyzed, multivariate analysis (Cox model) demonstrated that anterior commissure extension, arytenoid protection, and male gender were the worst independent prognostic factors in terms of local control. CONCLUSION: For early-stage laryngeal cancer, outcome after RT is excellent. In case of anterior commissure extension, surgery or higher RT doses are warranted. Because of a high relapse risk, arytenoid protection should not be attempted.     

Palliative Radiochemotherapie mit Bendamustin bei fortgeschrittenen Tumorrezidiven im HNO-Bereich

BACKGROUND: In case of recurrent carcinoma of the head and neck region therapeutic options are often limited due to intensive prior therapy and/or reduced physical condition of the patient. Nevertheless there is a need for palliative treatment to control symptoms like pain, obstruction of the airways, dysphagia and for hygienic and cosmetic reasons. Side effects, treatment time and achievable results have to be adjusted to the needs of this patient subgroup. PATIENTS AND METHOD: 14 patients (13 male, one female) with recurrent squamous cell carcinoma of the head and neck region were studied. Average age was 56.1 years (range 42-76 years) (Table 1). Prior therapy: radiotherapy n = 14 (42-71.3 Gy), surgery: n = 10, chemotherapy: n = 13 (Table 2). Our patients received 100-150 mg/m2 Bendamustin i.v. (day 1 and 2) and involved field irradiation 15 Gy (daily dose 3 Gy, day 1-5) (Figure 1). Remission status, time to progression, side effects and survival were documented. RESULTS: Ten patients showed partial remissions, four patients had complete remissions of the treated lesion (Figure 2), amelioration of 70% of tumor symptoms was documented (Figure 3). Time to progression was 2-104 weeks. Side effects: 71% of patients had no significant side effects, CTC Grade 3 to 4 toxicity was seen in two patients (14%). CONCLUSION: The reported therapy regimen allows successful palliative treatment of intensively pretreated patients with progressive recurrent tumors of the head and neck. Side effects are tolerable even in patients with reduced physical condition.     

Telethermographische Untersuchungen zur Wirkung von Immunglobulinen (Beriglobin®) auf das Wärmeabstrahlungsverhalten bei der Strahlendermatitis

Background

Immunoglobulines are supposed to have a soothing effect on the degree of dermatitides and mucositides caused by irradiation. Research so far has been based on empiric information or reports of case studies mostly basing on subjective criteria. This study reports on objective thermographic measuring of heat radiation of dermatitides developing in the course of radiotherapy in case of female patients receiving postoperative radiotherapy after breast preserving operation on mamma carcinoma. Idea behind this is that immunglobulines affect inflammations of skin induced by irradiation, then also one of theses parameters, in this case heat, would be subject to change.

Patients and Method

Sixteen patients received 10 ml Beriglobin^® before first and 5 ml after 5th and 10th radiation (corresponds to 0 Gy, 10 Gy and 20 Gy) as intragluteal injection. Before starting with radiation as well as after 10 Gy respectively applied, upper bodies of patients were examined thermographically until final dose of 50 Gy was reached. Here temperature progress on upper body halves exposed to irradiation was compared with the untreated halves as well as with upper bodies of control group consisting of 20 patients who had received no immunoglobuline injections.

Results

Patients who received immunoglobuline injections showed no differences in their skin temperature progress in comparison with the control group (Table 1, Figure 1). Skin temperature at the beginning as well as temperature progress during treatment and temperature at the end of treatment were identical in both groups. Also the relative temperature increase (temperature of body half subject to irradiation minus temperature of the other body half) was identical in both therapy groups (Table 2, Figure 2).

Conclusion

Immunoglobulines (Beriglobin^®) do not influence the course of thermal radiation due to dermatitis developing during a series of irradiation treatments. This results in the conclusion, that immunoglobulines do not have any influence in the vasodilatative part of dermatitis and vasodilatative redness respectively.     

Spättoxizität nach präoperativer Kurzzeitvorbestrahlung und risikoadaptierter postoperativer Nachbestrahlung bei operablem Rektumkarzinom Resultate einer randomisierten prospektiven Studie

AIM: Analysis of a randomized study of preoperative radiation therapy for operable carcinoma of the rectum with regard to late sequelae. Results of tumor control and survival, which have already been published in detail are summarized for comparison and for confirmation of the conclusions. PATIENTS AND METHODS: Between January 1988 and October 1993 94 patients with operable carcinoma of the rectum were included in a randomized trial. Fourty-seven patients were treated with 5 x 3.3 Gy (field size 16 x 16 cm, 9 MeV photons) 24 to 48 hours prior to surgery; 46 patients did not receive preoperative irradiation. If risk factors (T4-stage, R1/R2 resection, intraoperative tumor perforation) were present, postoperative irradiation was performed after CT-planning. Total postoperative doses of 41.4 Gy (preoperative irradiation) or 59.8 Gy (surgery only) were applied with doses per fraction of 1.8 to 2.0 Gy. Local control, survival, and pattern of side effects were analyzed at 5 years after conclusion of the trial. RESULTS: The frequency of local recurrence was markedly reduced by preoperative irradiation of R0-resected patients (24% vs 13%, p = 0.08). The time to recurrence was delayed (1.9 vs 3 years). The 5-year actuarial survival rate was significantly higher in the preoperatively irradiated group compared to the not pre-irradiated group (40% vs 28%, p = 0.027). Multivariate analysis revealed UICC-grading as the only independent parameter for local control (p = 0.0003), while preoperative irradiation (p = 0.07) and T-stage (p = 0.08) only displayed a trend. For patient survival, age (p = 0.0003). R-status (p = 0.01) and UICC-score (p = 0.001) were significant prognostic factors. Preoperative irradiation had a non-significant effect only (p = 0.078). Radiation-induced side effects with a LENT-SOMA score > 2 were observed neither during frequent follow-up nor at an additional examination of those patients still alive in 1998 (n = 25). Of 4 pre- and postoperatively irradiated patients with risk factors, 3 had side effects grade 1 or 2, predominantly rectal changes, at 5 to 11 years after treatment. CONCLUSIONS: A positive effect on tumor control and survival is achieved with preoperative irradiation with the doses used in this study, with moderate side effects.     

Phase I/II Trial of External Irradiation plus Medium-Dose Brachytherapy Given Concurrently to Liposomal Doxorubicin and Cisplatin for Advanced Uterine Cervix Carcinoma

BACKGROUND AND PURPOSE: Although the standard of care for patients with locally advanced uterine cervix carcinoma is cisplatin-(CDDP-)based chemotherapy and irradiation (RT), the optimal regimen remains to be elucidated. A phase I/II study was conducted to evaluate the dose limiting toxicity (DLT) and the maximum tolerated dose (MTD) of liposomal doxorubicin (Caelyx) combined with CDDP and RT for cervical cancer. PATIENTS AND METHODS: 24 patients with stage IIB-IVA were enrolled (Table 1). They all received external RT (up to 50.4 Gy) and two medium-dose rate (MDR) brachytherapy implants (20 Gy each at point A). The Caelyx starting dose of 7 mg/m2/week was increased in 5-mg/m2 increments to two levels. The standard dose of CDDP was 20-25 mg/m2/week. RESULTS: Concurrent chemoradiation (CCRT) sequelae and the DLTs (grade 3 myelotoxicity and grade 3 proctitis in five patients treated at the 17 mg/m2/week Caelyx dose level) are shown in Tables 2, 3, 4, and 5. After a median follow-up time of 17.2 months (range 4-36 months), four patients had died, 15 showed no evidence of progressive disease, and five (20.8%, 95% confidence interval [CI]: 12.5-29.1%) were alive with relapse (Figure 1). There were seven complete (29.1%, 95% CI: 19.8-38.4%) and 17 partial clinical responses (95% CI: 61.1-80.1%). The median progression-free survival was 10.4 months. Causes of death were local regional failure with or without paraaortic node relapse combined with distant metastases (Table 6). CONCLUSION: Conclusion: The MTD of Caelyx given concurrently with CDDP and RT was determined at the 12 mg/m2/week dose level. The above CCRT schema is a well-tolerated regimen, easy to administer in ambulatory patients, and results appear promising.     

Is 50 Gy Sufficient to Achieve Long-Term Local Control after Incomplete Resection of Typical Neurocytomas?

BACKGROUND AND PURPOSE: Central neurocytomas are generally described as rare benign central nervous system tumors. They can be divided in two groups, typical and atypical neurocytomas. Typical neurocytomas are associated with better outcome. This study investigates whether a decrease in radiation dose from 54 Gy to 50 Gy for incompletely resected typical neurocytomas would jeopardize the outcome. PATIENTS AND METHODS: The data of all reported neurocytoma patients were reviewed. Tumors with an atypical histology or an MIB-1 labeling index > 3% were defined as atypical neurocytomas and excluded from this analysis. If the reported data were incomplete, the authors were contacted for additional relevant data. Two groups were created based on an EQD2 (equivalent dose in 2-Gy fractions) of < or = 50 Gy or > 50 Gy and compared for overall survival and local control. Additionally, the patients who received an EQD2 < 50 Gy were compared to those patients receiving an EQD2 = 50 Gy. RESULTS: The data were complete in 94 patients. The 10-year survival was 100% after < or = 50 Gy (n = 34) and 93% after > 50 Gy (n = 60; p = 0.51). The 10-year local control rates were 83% and 88%, respectively (p = 0.69). At 10 years, overall survival was 100% both after < 50 Gy and after 50 Gy (p = 1.0), local control was 71% and 90%, respectively (p = 0.029). CONCLUSION: After incomplete resection of typical neurocytomas, radiotherapy with 50 Gy (2-Gy fractions) appears sufficient, as it resulted in similar local control as doses > 50 Gy and insignificantly better local control than doses < 50 Gy.     

Small bowel toxicity after high dose spot scanning-based proton beam therapy for paraspinal/retroperitoneal neoplasms

Purpose

Mesenchymal tumours require high-dose radiation therapy (RT). Small bowel (SB) dose constraints have historically limited dose delivery to paraspinal and retroperitoneal targets. This retrospective study correlated SB dose–volume histograms with side-effects after proton radiation therapy (PT).

Patients and methods

Between 1997 and 2008, 31 patients (mean age 52.1 years) underwent spot scanning-based PT for paraspinal/retroperitoneal chordomas (81?%), sarcomas (16?%) and meningiom (3?%). Mean total prescribed dose was 72.3 Gy (relative biologic effectiveness, RBE) delivered in 1.8–2 Gy (RBE) fractions. Mean follow-up was 3.8 years. Based on the pretreatment planning CT, SB dose distributions were reanalysed.

Results

Planning target volume (PTV) was defined as gross tumour volume (GTV) plus 5–7 mm margins. Mean PTV was 560.22 cm³. A mean of 93.2?% of the PTV was covered by at least 90?% of the prescribed dose. SB volumes (cm³) receiving doses of 5, 20, 30, 40, 50, 60, 70, 75 and 80 Gy (RBE) were calculated to give V5, V20, V30, V40, V50, V60, V70, V75 and V80 respectively. In 7/31 patients, PT was accomplished without any significant SB irradiation (V5?=?0). In 24/31 patients, mean maximum dose (Dmax) to SB was 64.1 Gy (RBE). Despite target doses of >?70 Gy (RBE), SB received >?50 and >?60 Gy (RBE) in only 61 and 54?% of patients, respectively. Mean SB volumes (cm³) covered by different dose levels (Gy, RBE) were: V20 (n?=?24): 45.1, V50 (n?=?19): 17.7, V60 (n?=?17): 7.6 and V70 (n?=?12): 2.4. No acute toxicity ≥ grade 2 or late SB sequelae were observed.

Conclusion

Small noncircumferential volumes of SB tolerated doses in excess of 60 Gy (RBE) without any clinically-significant late adverse effects. This small retrospective study has limited statistical power but encourages further efforts with higher patient numbers to define and establish high-dose threshold models for SB toxicity in modern radiation oncology.     

Radiotherapy for Orbital Lymphoma

PURPOSE: To analyze the effectiveness of radiotherapy in the management of orbital non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: 42 patients (median age 64.5 years) were reviewed retrospectively. The median follow-up period was 58 months. 26 patients had stage IE orbital lymphoma (22 indolent, four aggressive NHLs). 16 patients had advanced NHLs in stages II-IV with orbital involvement (eleven indolent, five aggressive NHLs). The median radiation dose was 40 Gy (20-46 Gy) for indolent lymphoma and 44 Gy (20-48 Gy) for aggressive lymphoma. Patients with stage IE were treated with at least 30 Gy. RESULTS: The 5-year local control rate for patients with stage I was 100%, the 5-year overall survival 91%. Two distant relapses were found, but no lymphoma-related death was detected. The 5-year local control rate for patients in stages II, III, and IV was 80%. Two local failures were detected. The 5-year overall survival for the advanced stages was 47%, nine patients with stages III and IV died due to systemic progression of lymphoma. Acute, radiotherapy-related complications grade 3/4 were not observed. Late effects grade 1/2 were documented in 45%. Six patients, treated with doses of > 36 Gy, developed grade 3 complications (four cataract, two dryness). CONCLUSION: Radiotherapy alone yields excellent local control and overall survival rates in orbital lymphoma stage IE. Local irradiation is also well tolerated and effective in advanced NHL stages with orbital infiltration. Doses of > 36 Gy resulted in an increase of late complications.     

Long-term Results of Radiotherapy in Patients with Chronic Palmo-plantar Eczema or Psoriasis

BACKGROUND AND PURPOSE: Radiotherapy (RT) is well accepted for therapy-refractory palmo-plantar eczema or psoriasis, despite of lacking evidence regarding beneficial long term effects. Furthermore, the optimal irradiation dose is unknown. We evaluated the outcome of RT with two different RT single/total dose (SD/TD) treatment policies. PATIENTS AND METHODS: 28 consecutive patients with therapy-refractory eczema (n = 22) or psoriasis (n = 6) of palms and/or soles were irradiated twice a week either with a D(max) SD of 1 Gy (6/98-5/03; median TD: 12 Gy) or 0.5 Gy (6/03-7/04; median TD: 5 Gy). Median age was 52 years (27-71), median follow-up 20 months (4-76). Totally 88 regions were treated, 49 with 1 Gy, 39 with 0.5 Gy SD. Eight different symptoms were scored from 0 (absent) -3 (severe), giving a possible sum score of 0-24. Patients' rating of RT result was also documented (worse/stable/better/complete remission). RESULTS: The sum score was 15 (6-23) before RT, 2 (0-16) at the end of RT, and 1 (0-21) at last follow-up, respectively. The improvement was highly significant in both treatment regimens. Better or complete remission by the patients were reported in 44 and 39 (= 83 out of 88) localisations, that was often stable during the follow-up. 5 (6%) regions in 3 (11%) patients didn't benefit from RT. CONCLUSION: RT reveals excellent results in palmo-plantar eczema or psoriasis. We recommend a SD of 0.5 Gy twice a week up to a TD of 4-5 Gy.     

The Efficiency and Tolerance of Half-Body Irradiation (HBI) in Patients with Multiple Metastases

AIM: To present our experience regarding the efficiency and tolerance of half-body irradiation in patients with multiple cancer metastases. PATIENTS AND METHODS: Between January 1986 and December 1997, 102 patients with multiple cancer metastases received half-body irradiation (HBI) at the Center of Oncology--Maria Sklodowska-Curie Memorial Institute in Krakow. Most of the patients (93/102) had bone metastases (Table 1). The HBI was performed with 9 MV photon beam from linear accelerator. In 88 patients only one region (upper, mid or lower) was treated, and 14 patients received upper and lower HBI (13 patients), or upper and mid HBI (one patient) (Table 2). The mean doses were: 6 Gy in upper HBI, 8 Gy in mid HBI, and 9 Gy in lower HBI (Table 3). RESULTS: The positive palliative effect (complete or partial pain relief) was observed in 77 (75.5%) patients (Table 4). Complete pain relief was higher in patients with prostate cancer, and in patients who received mid or lower HBI. During follow-up 47 (46.1%) patients developed pain progression after treatment (Table 5). The probability of survival without pain progression was higher in patients who developed complete pain relief (86.7% at 6 months, 69.3% at 12 and 24 months) than in patients with partial response (52.9% at 6 months, 32.8% at 12 months, and 5.5% at 24 months) (Figure 1). In most of the patients (74/102, 72.5%) the tolerance was good. CONCLUSIONS: HBI is an efficient method for palliation in patients with multiple painful metastases.     

CT-Guided Interstitial Brachytherapy of Primary and Secondary Lung Malignancies

BACKGROUND AND PURPOSE: CT-guided interstitial brachytherapy of primary lung malignancies and pulmonary metastases represents a novel interventional technique, combining conventional high-dose-rate (HDR) iridium-192 ((192)Ir) brachytherapy with modern CT guidance for applicator positioning and computer-aided 3-D radiation treatment planning. The purpose of this study was to assess safety and efficacy of this technique. PATIENTS AND METHODS: 30 patients with 83 primary or secondary lung malignancies were recruited in a prospective nonrandomized trial (Table 1). After catheter positioning under CT fluoroscopy, a spiral CT was acquired for treatment planning (Figure 1). All but two patients received a defined single dose (coverage > 99%) of at least 20 Gy from a (192)Ir source in HDR technique. RESULTS: Adverse effects were nausea (n = 3, 6%), minor (n = 6, 12%) and one major pneumothorax (2%). Post intervention, no changes of vital capacity and forced expiratory volume could be detected. The median follow-up period was 9 months (1-21 months) with a local tumor control of 91% at 12 months (Figure 2). CONCLUSION: CT-guided interstitial brachytherapy proved to be safe and effective for the treatment of primary and secondary lung malignancies.     

What is the optimal dose for 125I prostate implants? A dose-response analysis of biochemical control, posttreatment prostate biopsies, and long-term urinary symptoms

PURPOSE: To define the optimal dose for 125I prostate implants by correlating post implant CT dosimetry findings with urinary symptoms, biochemical failure, and posttreatment biopsies. METHODS AND MATERIALS: Patients with T1-T2, Gleason score 2-6 prostate cancer treated with I-125 brachytherapy were analyzed. Group 1 (276 patients) was observed from 18 to 108 months (median, 34 months) and had urinary symptoms prospectively assessed using the International Prostate Symptom Score (IPSS) system. Group 2 (181 patients) observed from 24 to 108 months (median, 44 months) and did not receive hormonal therapy. Implant dose was defined as the D90 (dose delivered to 90% of the prostate on a dose-volume histogram). Patients were analyzed by dose categories: <140 Gy, 140 to <160 Gy, 160 to <180 Gy, and > or =180 Gy. In Group 1, the mean pre- to postimplant IPSS scores were compared in different dose categories by using a matched paired t test. In Group 2, the effect of dose on biochemical control was tested with actuarial methods by using the American Society for Therapeutic Radiology and Oncology definition and on local control with posttreatment biopsies (113 patients). RESULTS: A comparison of pre- with postimplant IPSS revealed no significant changes in scores in the dose groups <180 Gy except for small changes in urgency and bladder emptying in the dose group <140 Gy. In dose group >180 Gy, mean scores changed from 0.5 to 1.0 (p=0.002) for emptying, 0.76 to 1.29 (p=0.004) for weak stream, 0.24 to 0.51 (p=0.009) for straining, 1.55 to 1.82 (p=0.05) for nocturia, and 6.3 to 8.45 (p=0.0009) for the total score. Freedom from biochemical failure (FFBF) at 5 years was 68% for doses <140 Gy, 97% for 140 to <160 Gy, 98% for 160 to <180 Gy, and 95% for > or =180 Gy (p=0.0025). Overall, patients with doses <140 Gy (median follow-up, 66 months) had an FFBF of 68%, compared with 96% for patients with doses > or =140 Gy (median follow-up, 35 months; p=0.0002). Multivariate analysis found dose to be the most significant factor affecting FFBF. Positive biopsies were found in 23% for doses <140 Gy, 21% for 140 to <160 Gy, 10% for 160 to <180 Gy, and 8% for > or =180 Gy. Overall, biopsies were positive in 22% for doses <160 Gy vs. 9% for > or =160 Gy (p=0.05). CONCLUSIONS: Optimal 125I prostate implants should deliver a D90 of 140-180 Gy, on the basis of postimplant dosimetry. Doses of <140 Gy are associated with increased biochemical failure, and doses >180 Gy with a small increase in long-term urinary symptoms.     

Transperineal Low-Dose Rate Iridium-192 Interstitial Brachytherapy in Cervical Carcinoma Stage IIB

PURPOSE: To assess local control, survival and complications in patients with cervical carcinoma Stage IIB treated radically with transperineal Iridium-192 low-dose rate interstitial brachytherapy following external beam radiotherapy. PATIENTS AND METHODS: 65 women (age 25-70 years, mean 47 years) with cervical carcinoma Stage IIB were initially treated with external beam radiotherapy on a telecobalt or 6 MV linear accelerator to a dose of 50 Gy delivered in 5-6 weeks. After 2-3 weeks of completing external radiation, patients received interstitial brachytherapy with Iridium-192 (activity 0.5-1 mCi/cm) using a Syed-Neblett perineal template. The median dose delivered to the implant volume was 24 Gy (range 20-32 Gy) delivered at an average dose rate of 0.70 Gy/h (range 0.40-1.20 Gy/h). A point defined at 1.5 cm lateral to the central uterine tandem at the level of os was taken as a representative for assessing the dose to the cervix. Mean doses delivered by interstitial brachytherapy to point A, cervix, point B and rectum were 38 Gy, 34 Gy, 16 Gy and 16 Gy, respectively. RESULTS: At a median follow-up of 53 months, the actuarial disease free survival and overall survival for 65 patients at both 5 and 10 years was 64% and 44%, respectively. Response to radiotherapy was a strong predictor of local control with 82% of patients continuing to have pelvic control after initial complete response. Overall, nine (14%) patients had persistent disease, ten (15%) developed a central recurrence after initial control and three patients developed distant metastasis on follow-up. No patient had any immediate treatment-related complication. Late toxicity included grade I-II rectal reactions in five patients and grade IV bladder complication (vesico-vaginal fistula) in two patients. 5 years after treatment, one patient developed intestinal obstruction, which was relieved after conservative management. Two patients developed vaginal stenosis. The 5- and 10-year disease free survival was 48% in patients aged less than 45 years as compared to 80% in patients of more than 45 years (p = 0.009). Dose to the cervical point was a prognostic indicator with 5- and 10-year disease free survival of 47% in patients who received < 35 Gy in comparison to 80% in patients who had > 35 Gy (p = 0.03). There was no difference in local control and survival in patients with minimal and moderate parametrial involvement. Bulky disease (> 4 cm) at presentation and a longer gap between external radiation and brachytherapy showed a trend towards inferior local control. CONCLUSIONS: Interstitial brachytherapy after external beam irradiation in patients with cervical carcinoma Stage IIB results in acceptable local control, survival and complication rates. Increased dose to the cervical disease results in improved local control and survival and should therefore be considered while optimizing brachytherapy treatment plans. Comparison of the results with those of standard intracavitary therapy remains to be proven in a randomized trial.     

Bestrahlung von Schädelbasistumoren mit Kohlenstoffionen bei der GSI Erste klinische Ergebnisse und zukünftige Perspektiven

BACKGROUND: Radiobiological and physical examinations suggest clinical advantages of heavy ion irradiation. We report the results of 23 women and 22 men (median age 48 years) with skull base tumors irradiated with carbon ion beams at the Gesellschaft für Schwerionenforschung (GSI), Darmstadt, from December 1997 until September 1999. PATIENTS AND METHODS: The study included patients with chordomas (17), chondrosarcomas (10) and other skull base tumors (Table 1). It is the first time that the intensity-controlled rasterscan-technique and the application of positron-emission tomography (PET) for quality assurance was used. All patients had computed tomography for three-dimensional-treatment planning (Figure 1). Patients with chordomas and chondrosarcomas underwent fractionated carbon ion irradiation in 20 consecutive days (median total dose 60 GyE). Other histologies were treated with a carbon ion boost of 15 to 18 GyE delivered to the macroscopic tumor after fractionated stereotactic radiotherapy (median total dose 63 GyE). RESULTS: Mean follow-up was 9 months. Irradiation was well tolerated by all patients. Partial tumor remission was seen in 7 patients (15.5%) (Figure 2). One-year local control rate was 94%. One patient (2.2%) deceased. No severe toxicity and no local recurrence within the treated volume were observed. CONCLUSION: Clinical effectiveness and technical feasibility of this therapy modality could clearly be demonstrated in our study. To evaluate the clinical relevance of the different beam modalities studies with larger patient numbers are necessary. To continue our project a new heavy ion accelerator exclusively for clinical use is planned to be constructed in Heidelberg.     

Prospective assessment of patient-reported long-term urinary morbidity and associated quality of life changes after 125I prostate brachytherapy

PURPOSE: Prostate brachytherapy has been reported to have less morbidity for patients than radical prostatectomy or external beam irradiation. However, to date there have been no long-term data to support these claims. With radiation doses in excess of 140 Gy required to control the tumor, disabling chronic urinary symptoms and associated quality of life (QOL) changes might be expected to occur. This study prospectively assessed the long-term effects of (125)I prostate brachytherapy on urinary morbidity. METHODS AND MATERIALS: A total of 248 patients with a median age of 67 years (range, 43-83 years) who presented with T1-T2 prostate cancer were treated with (125)I seed implantation and followed up for a minimum of 18 months after treatment (range, 18 to 108 months; median, 31 months). There were 177 T1b-T2a cases and 41 patients with prostate-specific antigen >10 ng/ml; 20.2% were treated with hormonal therapy. All patients prospectively reported their urinary symptoms and QOL assessment on American Urological Association symptom score records before treatment and at each follow-up visit. Urinary symptoms at last follow-up were compared with pretreatment scores. Radiation doses to the prostate (dose delivered to 90% of the gland; D(90)) and urethra (D(30)) were determined by CT-based dosimetry. RESULTS: The median prostate D(90) was 165 Gy (range, 16.5-260 Gy), and the median urethra D(30) was 192 Gy (range, 23.5-306 Gy). Mean individual scores and QOL ranged from 0.31 to 1.65 before implantation and 0.39 to 1.73 afterward. There were no significant differences between pretreatment and last mean scores for any of the categories except for a small but significant increase in urgency (p=0.01) and weak stream (p=0.03). The cohort of patients who initially presented with marked urinary symptoms (initial score >or=3) had improvement in individual scores by 31.4% to 58.2%, total score by 31.1% (p=0.0005), and QOL by 40.6% (p<0.0001). CONCLUSIONS: This study suggests that prostate brachytherapy is associated with minimal long-term urinary morbidity. The subgroup of patients who present with marked urinary symptoms before implantation has improvement in symptoms and QOL after implantation. These data substantiate the favorable long-term QOL outcomes associated with modern brachytherapy techniques.