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M Flentje

Publications and source records attributed to M Flentje.

At least 37 records · Page 2Linked to original sources
PubMed2000

The influence of the radicality of resection and dose of postoperative radiation therapy on local control and survival in carcinomas of the upper aerodigestive tract.

PURPOSE: To evaluate dose concepts in postoperative irradiation of carcinomas of the upper aerodigestive tract according to the radicality of resection. PATIENTS AND METHODS: In a retrospective analysis, the charts of 257 patients with histologically-proven carcinoma of the upper aerodigestive tract (40 T1, 80 T2, 53 T3, 84 T4 tumors, with nodal involvement in 181 cases) were reviewed according to the radicality of resection and dose of irradiation administered. Sixty-four patients had tumor-free resection margins (> 3 mm), 66 patients had close resection margins (< 3 mm), and 101 patients had R1 resections, and 26 patients had R2 resections. A median dose of 56 Gy was applied to the primary tumor bed and the cervical lymphatics (2 Gy/fraction, 5 fractions/week). In cases of R1 or R2 resection, or of close margins (< 3 mm), the tumor bed or, respectively, tumor residuals were boosted with doses up to a median of 66 Gy. Locoregional tumor control and survival was investigated by uni- and multivariate analyses according to T-, N-stage, grade of resection, total dose of radiation, and presence or absence of extracapsular tumor spread and lymphangiosis carcinomatosa. RESULTS: An overall 3- and 5-year survival rate of 60% and 45%, respectively, was achieved. Rates for freedom from locoregional recurrence were 77% and 72% at 3 and 5 years, respectively. The survival rates according to the grade of resection at 5 years were 67% for patients resected with tumor-free margins, 59% for patients resected with close margins, 26% for patients with R1 resection, and 27% for patients with R2 resection. Within a median follow-up period of 4.7 years for living patients, a total of 67 recurrences (26%) were observed (in 9% of patients resected with tumor-free margins, in 27% with close margins, in 37% of R1 resected, and in 19% of R2 resected patients). Freedom from locoregional recurrence at 3 years was achieved in 100% of the patients resected with tumor-free margins, in 92% of patients resected with close surgical margins, in 87% of R1 and 69% of R2 resected patients. In multivariate Cox-regression analysis, the variables grade of resection (p = 0.00031) and total dose of irradiation (p = 0.0046) were found as factors influencing locoregional control. Variables influencing survival according to multivariate analysis are T-stage (p = 0.0057), N-stage (p = 0.024), grade of resection (p = 0.000015), total dose of irradiation (p < 0. 000000). Extracapsular tumor spread and lymphangiosis carcinomatosa are factors of borderline significance (p = 0.055, p = 0.066). CONCLUSION: In postoperative radiotherapy of head and neck carcinomas, doses adapted to the risk of locoregional recurrent disease should be applied. Patients with R1 and R2 resections should be treated with doses of more than 68 Gy (2 Gy/fraction, 5 fractions/week) (with close margins [< 3 mm] more than 66 Gy) to achieve an improvement in locoregional control and survival.

Adult↗
PubMed2000

Transcranial sonography: integration into target volume definition for glioblastoma multiforme.

PURPOSE: Recent studies indicate that transcranial sonography (TCS) reliably displays the extension of malignant brain tumors. The effect of integrating TCS into radiotherapy planning for glioblastoma multiforme (GBM) was investigated herein. METHODS AND MATERIALS: Thirteen patients subtotally resected for GBM underwent TCS during radiotherapy planning and were conventionally treated (54 to 60 Gy). Gross tumor volumes (GTVs) and stereotactic boost planning target volumes (PTVs, 3-mm margin) were created, based on contrast enhancement on computed tomography (CT) only (PTV(CT)) or the combined CT and TCS information (PTV(CT+TCS)). Noncoplonar conformal treatment plans for both PTVs were compared. Tumor progression patterns and preoperative magnetic resonance imaging (MRI) were related to both PTVs. RESULTS: A sufficient temporal bone window for TCS was present in 11 of 13 patients. GTVs as defined by TCS were considerably larger than the respective CT volumes: Of the composite GTV(CT+TCS) (median volume 42 ml), 23%, 13%, and 66% (medians) were covered by the overlap of both methods, CT only and TCS only, respectively. Median sizes of PTV(CT) and PTV(CT+TCS) were 34 and 74 ml, respectively. Addition of TCS to CT information led to a median increase of the volume irradiated within the 80% isodose by 32 ml (median factor 1.51). PTV(CT+TCS) volume was at median 24% of a "conventional" MRI(T2)-based PTV. Of eight progressions analyzed, three and six occurred inside the 80% isodose of the plans for PTV(CT) and for PTV(CT+TCS), respectively. CONCLUSION: Addition of TCS tumor volume to the contrast-enhancing CT volume in postoperative radiotherapy planning for GBM increases the treated volume by a median factor of 1.5. Since a high frequency of marginal recurrences is reported from dose-escalation trials of this disease, TCS may complement established methods in PTV definition.

Adult↗
PubMed2000

Postoperative neoadjuvant chemotherapy before radiotherapy as compared to immediate radiotherapy followed by maintenance chemotherapy in the treatment of medulloblastoma in childhood: results of the German prospective randomized trial HIT '91.

PURPOSE: The German Society of Pediatric Hematology and Oncology (GPOH) conducted a randomized, prospective, multicenter trial (HIT '91) in order to improve the survival of children with medulloblastoma by using postoperative neoadjuvant chemotherapy before radiation therapy as opposed to maintenance chemotherapy after immediate postoperative radiotherapy. METHODS AND MATERIALS: Between 1991 and 1997, 158 patients were enrolled and 137 patients randomized. Seventy-two patients were allocated to receive neoadjuvant chemotherapy before radiotherapy (arm I, investigational). Chemotherapy consisted of ifosfamide, etoposide, intravenous high-dose methotrexate, cisplatin, and cytarabine given in two cycles. In arm II (standard arm), 65 patients were assigned to receive immediate postoperative radiotherapy, with concomitant vincristine followed by 8 cycles of maintenance chemotherapy consisting of cisplatin, CCNU, and vincristine ("Philadelphia protocol"). All patients received radiotherapy to the craniospinal axis (35.2 Gy total dose, 1.6 Gy fractionated dose / 5 times per week followed by a boost to posterior fossa with 20 Gy, 2.0 Gy fractionated dose). RESULTS: During chemotherapy Grade III/IV infections were predominant in arm I (40%). Peripheral neuropathy and ototoxicity were prevailing in arm II (37% and 34%, respectively). Dose modification was necessary in particular in arm II (63%). During radiotherapy acute toxicity was mild in the majority of patients and equally distributed in both arms. Myelosuppression led to a mean prolongation of treatment time of 11.5 days in arm I and 7.5 days in arm II, and interruptions in 35% of patients in arm I. Quality control of radiotherapy revealed correct treatment in more than 88% for dose prescription, more than 88% for coverage of target volume, and 98% for field matching. At a median follow-up of 30 months (range 1.4-62 months), the Kaplan-Meier estimates for relapse-free survival at 3 years for all randomized patients were 0.70+/-0.08; for patients with residual disease: 0.72+/-0.06; without residual disease: 0.68+/-0.09; M0: 0.72+/-0.04; M1: 0.65+/-0.12; and M2/3: 0.30+/-0.15. For all randomized patients without M2/3 disease: 0.65+/-0.05 (arm I) and 0.78+/-0.06 (arm II) (p < 0.03); patients between 3 and 5.9 years: 0.60+/-0.13 and 0.64+/-0.14, respectively, but patients between 6 and 18 years: 0.62+/-0.09 and 0.84+/-0.08, respectively (p < 0.03). In a univariate analysis the only negative prognostic factors were M2/3 disease (p < 0.002) and an age of less than 8 years (p < 0.03). CONCLUSIONS: Maintenance chemotherapy would seem to be more effective in low-risk medulloblastoma, especially in patients older than 6 years of age. Neoadjuvant chemotherapy was accompanied by increased myelotoxicity of the subsequent radiotherapy, causing a higher rate of interruptions and an extended overall treatment time. Delayed and/or protracted radiotherapy may therefore have a negative impact on outcome. M2/3 disease was associated with a poor survival in both arms, suggesting the need for a more intensive treatment. Young age and M2/3 stage were negative prognostic factors in medulloblastoma, but residual or M1 disease was not, suggesting a new stratification system for risk subgroups. High quality of radiotherapy may be a major contributing factor for the overall outcome.

Adolescent↗
PubMed2000

Cataract incidence after total-body irradiation.

PURPOSE: The aim of this retrospective study was to evaluate cataract incidence in a homogeneously-treated group of patients after total-body irradiation (TBI) followed by autologous bone marrow transplantation or peripheral blood stem cell transplantation. METHODS AND MATERIALS: Between 1982 and 1994, a total of 260 patients received either autologous bone marrow or blood stem cell transplantation for hematological malignancy at the University of Heidelberg. Two hundred nine of these patients received TBI in our hospital. Radiotherapy was applied as hyperfractionated TBI, with a median dose of 14.4 Gy in 12 fractions over 4 days. Minimum time between fractions was 4 h. Photons with an energy of 23 MeV were used with a dose rate of 7-18 cGy/min. Ninety-six of the 209 irradiated patients were still alive in 1996; 86 of these patients (52 men, 33 women) answered a questionnaire and could be examined ophthalmologically. The median age at time of TBI was 38.5 years, with a range of 15-59 years. RESULTS: The median follow-up is now 5.8 years, with a range of 1.7-13 years. Cataract occurred in 28/85 patients (32.9%) after a median of 47 months (1-104 months). In 6 of 28 patients who developed a cataract, surgery of the cataract was performed. Whole-brain irradiation prior to TBI had been performed more often in the group of patients developing cataract (14.3%) versus 10.7% in the group of patients without cataract. However, there was no statistical difference (Chi-square, p>0.05). CONCLUSION: Cataract is a common side effect of TBI. Cataract incidence found in our patients is comparable to results of other centers using a fractionated regimen for TBI. To assess the incidence of cataract after TBI, a long-term follow-up is required.

Adult↗
PubMed2000

The Internet as a source of medical information. Investigation in a mixed cohort of radiotherapy patients.

BACKGROUND: The widespread use of the internet has influenced patterns of medical information for tumor patients. The present study examines the use of various media and, in particular, the application of the internet, in a mixed cohort of radiotherapy patients. PATIENTS AND METHODS: All patients undergoing radiotherapy at the University of Würzburg were analyzed simultaneously in May of 2000 using a newly developed 9-item questionnaire. Questions related to the importance of various media for medical information (grading from 0 = unimportant to 2 = very important) and previous internet use. The data was correlated with clinical information from the patients' charts. RESULTS: In 95% of patients (n = 139) questionnaires were evaluable. Of 8 media, television (mean score 0.94), patient brochure (0.83) and newspaper (0.76) were considered most important for medical information while the internet ranged last (0.24). Whereas 61.2% knew the internet as a source of medical information, only 11.5% had searched the internet themselves and 15.1% had received internet information from family or friends. Only 24.1% from these 2 groups had discussed the information with their physician. The rates of internet use were substantially higher in subgroups with younger age, higher education and palliative treatment. CONCLUSION: The importance of the medium internet for the information of tumor patients is currently still low but likely to increase based on demographic factors.

Adult↗
PubMed2000

Influence of treatment technique on dose-volume histogram and normal tissue complication probability for small bowel and bladder. A prospective study using a 3-D planning system and a radiobiological model in patients receiving postoperative pelvic irradiation.

PURPOSE: A prospective study was undertaken to evaluate the influence of pelvic irradiation techniques on the dose-volume histograms of organs at risk and to analyze its possible clinical relevance using radiobiological models. PATIENTS AND METHODS: For 20 patients receiving postoperative pelvic irradiation because of rectal cancer a 3-field technique (3-FT), a 4-field technique (4-FT) and an opposing field technique (OFT) were designed by a 3-D planning system (Helax, TMS). Dose-volume histograms (DVH) of small bowel, urinary bladder and planning target volume (PTV) were analyzed. The normal tissue complication probability (NTCP) was determined by the radiobiological model of Lyman and Kutcher using the tolerance data of Emami. RESULTS: Median dose to the PTV did not differ between the 3 techniques (3-FT/4-FT/OFT: 99.2%/98.6%/98.1% of the prescribed dose; p > 0.05). Although the median dose to the urinary bladder was lower for the 3-FT than for the 4-FT (44.7% vs 60.3%; p < 0.001), there was no difference in the calculated NTCP (0.0% vs 0.0%; p > 0.05). Using multiple field techniques both the dose to and the treated volume of the urinary bladder were significantly lower than using the OFT. As a consequence of this the late NTCP of the bladder was higher for the OFT (5.46%). Although the median dose to the small bowel was lower for the 3-FT than for the 4-FT (30.8% vs 54.5%; p < 0.005), the fractional part of small bowel within the high-dose region (90% isodose) was higher for the 3-FT (10.6% vs 8.2%; p > 0.05). Thus the calculated NTCP was higher for the 3-FT (0.79 vs 0.44) than for 4-FT. For the OFT the median dose to small bowel was 69.9% and the small bowel volume within the high-dose region was 57.8% resulting in a late NTCP of 9.36% (OFT vs 3-FT/4-FT: p < 0.05). CONCLUSION: Using multiple field techniques both the dose to the organs of risk and the fractional part of risk organs within the high-dose region can be reduced significantly. As a consequence of this a lower NTCP was calculated for the 3-FT and the 4-FT than for the OFT. Using the biological model a small, but significant difference between a 3-FT and a 4-FT was demonstrated in favor to the 4-FT.

Adult↗
PubMed2000

The postoperative adjuvant radiation therapy and radiochemotherapy for UICC stage II and III rectal cancer. A retrospective analysis.

AIM: This analysis was undertaken to review the outcome and toxicity of postoperative adjuvant therapy for Stage II and III rectal cancer. PATIENTS AND METHODS: We reviewed 112 patients treated with radiotherapy (44 patients) and radiochemotherapy (68 patients) after potentially curative (R0) surgery for rectal cancer (UICC Stages II and III), between 1983 and 1994 at the University Clinic of Würzburg. Median radiation dose was 56 Gy (range: 45 to 66 Gy). Chemotherapy consisted of 4 to 6 courses of 5-fluorouracil (5-FU) (420 mg/m2/d) and leucovorin (200 mg/m2/d). Median follow-up was 37 months. RESULTS: The overall survival was 84% for patients with UICC Stage II and 45% for patients with UICC Stage III disease (p = 0.0045). There were no statistically significant differences between patients treated with radiochemotherapy vs radiotherapy in terms of 5-year survival (63% after radiochemotherapy vs 53% after radiotherapy, p = 0.16), relapse-free survival (52% vs 50%) and locoregional control (69% vs 67%). UICC Stage III disease was associated with high failure rates (40% pelvic recurrences and 53% distant metastases). There was a statistically significant difference in terms of the incidence of distant metastases between the 2 treatment modalities for patients with Stage III disease (49% 5-year probability for developing distant metastases after radiochemotherapy vs 66% after radiotherapy, p = 0.047). In a multivariate analysis, the addition of chemotherapy, lymph node stage and grading were independent prognostic factors for survival. Severe late toxicity was documented in 5% of treated patients. CONCLUSIONS: Prognosis of patients with UICC Stage III rectal cancer remains poor after "standard" surgery followed by postoperative adjuvant treatment (pelvic radiotherapy and bolus intravenous injection of 5-FU and leucovorin). Major efforts should be made in order to improve prognosis for these patients, including optimization of surgical treatment and systemic treatment. More effective multimodality treatment strategies should be investigated in prospective randomized trials.

Adult↗
PubMed2000

A new verification film system for routine quality control of radiation fields: Kodak EC-L.

BACKGROUND: The use of modern irradiation techniques requires better verification films for determining set-up deviations and patient movements during the course of radiation treatment. This is an investigation of the image quality and time requirement of a new verification film system compared to a conventional portal film system. MATERIAL AND METHODS: For conventional verifications we used Agfa Curix HT 1000 films which were compared to the new Kodak EC-L film system. 344 Agfa Curix HT 1000 and 381 Kodak EC-L portal films of different tumor sites (prostate, rectum, head and neck) were visually judged on a light box by 2 experienced physicians. Subjective judgement of image quality, masking of films and time requirement were checked. RESULTS: In this investigation 68% of 175 Kodak EC-L ap/pa-films were judged "good", only 18% were classified "moderate" or "poor" 14%, but only 22% of 173 conventional ap/pa verification films (Agfa Curix HT 1000) were judged to be "good". CONCLUSIONS: The image quality, detail perception and time required for film inspection of the new Kodak EC-L film system was significantly improved when compared with standard portal films. They could be read more accurately and the detection of set-up deviation was facilitated.

Humans↗
PubMed2000

[Optimized 3-D planning by simple means. An example].

AIM: A treatment technique favorable for linacs with asymmetric jaws, which combines cranio-caudal matching fields with fields enclosing the whole target volume, is investigated with respect to field matching and sparing of normal tissue and organs at risk. PATIENT AND METHODS: For a pelvic target volume rapidly varying in cranio-caudal direction a 5-field technique was planned with individually weighted and blocked fields. Three fields adjoining in cranio-caudal direction were completed by 2 fields enclosing the whole target volume. The matching line was measured and calculated with Helax TMS. Furthermore a 4-field box and opposing fields were planned. The dose-volume histograms for target, bladder, intestine and soft tissue were exported. Normal tissue complication probability and tumor control probability, respectively, were calculated for all techniques. RESULTS: In the region of the matching line the summation of the measured normalized curves resulted in relative dose maxima of 6.0% (caudal) and 4.5% (cranial), respectively. For fields enclosing the whole target volume the dose maxima in the region of the matching line decreased to 2.0% (caudal) and 1.8% (cranial), respectively. For the dose profiles calculated with Helax TMS no overdose was found. The 5-field technique with adjoining fields results in a better sparing of the organs at risk compared to the other techniques, whereas the tumor control remains the same. CONCLUSIONS: In specific cases a technique with cranio-caudal adjoining fields can be recommended with respect to sparing of normal tissue and organs at risk.

Humans↗
PubMed2000

Radiation techniques for head and neck tumors.

PURPOSE: A technique that combines some advantages of conforming techniques for advanced oro- and hypopharyngeal carcinomas is proposed. The aim is to increase the dose homogeneity in the target volume relative to lateral opposed fields. METHODS AND MATERIALS: This publication compares conforming radiation techniques based on standard equipment, standard linear accelerator setup and commercially available planning software with lateral opposed fields. More advanced conformal techniques reported in the literature are taken into account in a semi-quantitative manner. Our standard method uses an arc rotation, sparing the spinal cord. In contrast to earlier methods of this type, the resulting dose deficit in the vicinity of the spine is compensated by static lateral wedged fields. Dose distributions for 25 consecutive patients were planned. RESULTS: The conforming techniques were found to produce more homogeneous dose distributions than lateral opposed fields. In the planning target volume (PTV) (mean: 940 cm(3)) a standard deviation of dose of 4.6% was achieved. Ninety-five percent of the PTV were enclosed by the 90% isodose. The maximal spinal cord dose was limited to 45 Gy. The dose distributions of these techniques could compete with literature data on advanced techniques (the published dose-volume histogram (DVHs) of PTVs were evaluated). At the linear accelerator time for realization took 14 min on average. The planning time is 1-4 h (mean: less than 2 h). CONCLUSION: A rotational technique applicable with standard equipment is presented. Dose coverage of target volumes is improved, while the spinal cord is spared.

Female↗
PubMed2000

Stereotactic radiotherapy of extracranial targets: CT-simulation and accuracy of treatment in the stereotactic body frame.

BACKGROUND AND PURPOSE: Evaluation of set-up accuracy and analysis of target reproducibility in the stereotactic body frame (SBF), designed by Blomgren and Lax from Karolinska Hospital, Stockholm. Different types of targets were analyzed for the risk of target deviation. The correlation of target deviation to bony structures was analyzed to evaluate the value of bones as reference structures for isocenter verification. MATERIALS AND METHODS: Thirty patients with 32 targets were treated in the SBF for primary or metastatic peripheral lung cancer, liver metastases, abdominal and pelvic tumor recurrences or bone metastases. Set-up accuracy and target mobility were evaluated by CT-simulation and port films. The contours of the target at isocenter level, bony structures and body outline were compared by matching the CT-slices for treatment planning and simulation using the stereotactic coordinates of the SBF as external reference system. The matching procedure was performed by using a 3D treatment planning program. RESULTS: Set-up accuracy represented by bony structures revealed standard deviations (SD) of 3.5 mm in longitudinal, 2.2 mm in anterior-posterior and 3.9 mm in lateral directions. Target reproducibility showed a SD of 4.4 mm in longitudinal, 3.4 mm ap and 3.3 mm in lateral direction prior to correction. Correlation of target deviation to bones ranged from 33% (soft tissue targets) to 100% (bones). CONCLUSION: A security margin of 5 mm for PTV definition is sufficient, if CT simulation is performed prior to each treatment to correct larger target deviations or set-up errors. Isocenter verification relative to bony structures is only safe for bony targets but not for soft tissue targets.

Adult↗
PubMed2000

[Results of radiotherapy in rectal carcinoma].

Adjuvant combined radio-chemotherapy in rectal cancer is indicated in stage UICC II and III (pT3/4 and/or pN+) without distant metastases (exception: resectable metastases of the liver). Radiotherapy alone improves local control in the pelvis. A statistical significant improvement of survival is only achievable in combination with systemic chemotherapy. In Germany neo-adjuvant, conventional fractionated radio-chemotherapy over five weeks is applied in patients with surgically inoperable tumors to achieve a "down-staging" with improvement of resectability. Neo-adjuvant radiotherapy of operable rectal cancer in five fractions of high single doses within one week has revealed a statistical significant improvement of survival if compared to surgery alone in the Swedish rectal cancer trial, but is not standard in Germany yet. The influence of technical advances in surgery as total mesorectal excision (TME) on indications of adjuvant therapy is evaluated in prospective randomized studies at this time.

Chemotherapy, Adjuvant↗
PubMed1999

Influence of patient positioning on dose-volume histogram and normal tissue complication probability for small bowel and bladder in patients receiving pelvic irradiation: a prospective study using a 3D planning system and a radiobiological model.

PURPOSE: A prospective study was undertaken to evaluate the influence of patient positioning (prone position using a belly board vs. supine position) on the dose-volume histograms (DVHs) of organs of risk, and to analyze its possible clinical relevance using radiobiological models. METHODS AND MATERIALS: From November 1996 to August 1997 a computed tomography (CT) scan was done in the prone position using a belly board and in supine position in 20 consecutive patients receiving postoperative pelvic irradiation because of rectal cancer. Using a three-dimensional (3D) planning system (Helax, TMS) the DVH for small bowel, bladder, a standard planning target volume (PTV) of postoperative irradiation of rectal cancer, the intersection of volume of PTV and small bowel (PTV intersection V(SB), respectively, of PTV and bladder (PTV intersection V(B)) were defined in each axial CT slice. The normal tissue complication probability (NTCP) was determined by the radiobiological model of Lyman and Kutcher using the tolerance data of Emami. For evaluation of late toxicity alpha/beta ratio was 2.5; for evaluation of acute toxicity, it was 10. Total dose was 50.4 Gy (1.8 Gy/fraction) (ICRU 50). RESULTS: Using the prone position compared to the supine position, the median volume of PTV intersection V(B) was reduced by 18.5 cm3 (62%). Median dose (related to the reference dose) to the bladder was 44.5% (22.4 Gy) in prone and 66.05% (33.3 Gy) in supine position (p<0.001). Median V(B) within the 90% (45.4 Gy), 80% (40.3 Gy), 60% (30.2 Gy), and 40% (20.2 Gy) isodose was significantly lower in the prone position when compared to the supine position. Using the radiobiological models, however, there was no difference of NTCP between prone position or supine position. In the prone position, median volume of PTV intersection V(SB) was reduced by 32.5 cm3 (54%). The median dose to small bowel was 30.85% (15.4 Gy) in the prone position and 47.35% (23.9Gy) in the supine position (p<0.001). Significant differences between prone and supine position were found for median V(SB) within the 90% (45.4 Gy), 80% (40.3 Gy), 60% (30.2 Gy), and 40% (20.2 Gy) isodose. According to the method of Lyman, median NTCP of small bowel was significant lower in prone than in supine position. CONCLUSION: The prone position with a standard belly board should be the standard positioning technique for patients receiving adjuvant postoperative radiation therapy following surgery of rectal cancer. Both irradiated volume and total dose to the organs of risk can be reduced significantly. As a consequence of this, radiation induced toxicity will be minimized.

Adult↗
PubMed1999

Sequence analysis of the ATM gene in 20 patients with RTOG grade 3 or 4 acute and/or late tissue radiation side effects.

PURPOSE: Patients with ataxia-telangiectasia (A-T) show greatly increased radiation sensitivity and cancer predisposition. Family studies imply that the otherwise clinically silent heterozygotes of this autosomal recessive disease run a 3.5 to 3.8 higher risk of developing cancer. In vitro studies suggest moderately increased cellular radiation sensitivity of A-T carriers. They may also show elevated clinical radiosensitivity. We retrospectively examined patients who presented with severe adverse reactions during or after standard radiation treatment for mutations in the gene responsible for A-T, ATM, considering a potential means of future identification of radiosensitive individuals prospectively to adjust dosage schedules. MATERIAL AND METHODS: We selected 20 cancer patients (breast, 11; rectum, 2; ENT, 2; bladder, 1; prostate, 1; anus, 1; astrocytoma, 1; Hodgkins lymphoma, 1) with Grade 3 to 4 (RTOG) acute and/or late tissue radiation side effects by reaction severity. DNA from the peripheral blood of patients was isolated. All 66 exons and adjacent intron regions of the ATM gene were PCR-amplified and examined for mutations by a combination of agarose gel electrophoresis, single-stranded conformational polymorphism (SSCP) analysis, and exon-scanning direct sequencing. RESULTS: Only 2 of the patients revealed altogether four heteroallelic sequence variants. The latter included two single-base deletions in different introns, a single-base change causing an amino acid substitution in an exon, and a large insertion in another intron. Both the single-base deletions and the single-base change represent known polymorphisms. The large insertion was an Alu repeat, shown not to give rise to altered gene product. CONCLUSIONS: Despite high technical efforts, no unequivocal ATM mutation was detected. Nevertheless, extension of similar studies to larger and differently composed cohorts of patients suffering severe adverse effects of radiotherapy, and application of new technologies for mutation detection may be worthwhile to assess the definite prevalence of significant ATM mutations within the group of radiotherapy patients with adverse reactions. To date, it must be recognized that our present results do not suggest that heterozygous ATM mutations are involved in clinically observed radiosensitivity but, rather, invoke different genetic predisposition or so far unknown exogenous factors.

Adult↗
PubMed1999

Carcinoma of the external auditory canal and middle ear.

PURPOSE: To evaluate therapeutic modalities used at our institutions regarding local control, disease-free survival and actuarial survival in carcinoma of the external auditory canal and middle ear, in an attempt to provide guidelines for therapy. METHODS AND MATERIALS: A series of 27 patients with carcinoma of the external auditory canal and middle ear treated between 1978 and 1997 in our institutions were analyzed with particular reference to tumor size and its relation to surrounding tissues, patterns of neck node involvement, surgical procedures, and radiation techniques employed. Clinical endpoints were freedom from local failure, overall survival, and disease-free survival. The median follow-up was 2.7 years (range 0.1-17.9 years). RESULTS: Treatment by surgery and radiotherapy resulted in an overall 5-year survival rate of 61%. According to the Pittsburgh classification, the actuarial 5-year survival rate for early disease (T1 and T2 tumors) was 86%, for T3 tumors 50%, and T4 stages 41%. Patients with tumors limited to the external auditory canal had a 5-year survival rate of 100%, patients with tumor invasion of the temporal bone 63%, and patients with tumor infiltration beyond the temporal bone 38%. The rate of freedom from local recurrence was 50% at 5 years. Unresectability by dural and cerebral infiltration, and treatment factors such as complete resection or resection with tumor beyond surgical margins are of prognostic relevance. All patients with dural invasion died within 2.2 years. The actuarial 5-year survival rate of patients with complete tumor resection was 100%, but 66% in patients with tumor beyond surgical margins. 192Iridium high-dose-rate (HDR) afterloading brachytherapy based on three-dimensional computed tomography (3D CT)-treatment planning was an effective tool in management of local recurrences following surgery and a full course of external beam radiotherapy. CONCLUSION: Surgical resection followed by radiotherapy adapted to stage of disease and grade of resection is the preferred treatment of cancer of the external auditory canal and middle ear.

Adult↗
PubMed1999

HIT '91 (prospective, co-operative study for the treatment of malignant brain tumors in childhood): accuracy and acute toxicity of the irradiation of the craniospinal axis. Results of the quality assurance program.

BACKGROUND: It was the aim of the quality control program of the randomized trial HIT '91 (intensive chemotherapy before irradiation versus maintenance chemotherapy after irradiation) to assess prospectively the quality of neuroaxis irradiation with respect to the protocol guidelines and to evaluate acute toxicity with respect to treatment arm. PATIENTS, MATERIALS AND METHODS: Data of 134 patients undergoing irradiation of the craniospinal axis were available. Positioning aids, shielding techniques, treatment machines, choice of energy, total dose and fractionation were evaluated. A total of 651 simulation and verification films were analyzed to assess the coverage of the clinical target volume (whole brain, posterior fossa, sacral nerve roots) and deviations of field alignment between simulation and verification of first treatment. Field matching between whole brain and adjacent cranial spinal fields was analyzed with respect to site and width of junction. Acute maximal side effects were evaluated according to a modified WHO score for neurotoxicity, infections, skin, mucosa and myelotoxicity. RESULTS: In 91.3% of patients contemporary positioning aids and individualized shielding techniques were used to assure a reproducible treatment. In 98 patients (73.1%) linear accelerators and in 36 patients (26.8%) Cobalt machines were used. Single and total dose were administered according to the protocol guidelines in more than 90% of patients. In 20.2% of patients the cribriform plate, in 1.4% the middle cranial fossa and in 21.1% the posterior fossa and in 4.5% the 2nd sacral segment were incompletely encompassed by the treatment portals. Ninety-five percent of deviations of field alignment were less than 13.0 mm (whole brain) and 12 mm (cranial spinal field) with a random error between 4.9 and 7.6 mm (whole brain) and 6.9 mm and 9.9 mm (spinal canal), respectively. In 77.5% of patients the junctions between whole brain and cranial spinal fields were placed without a gap. A gap between 5 and 10 mm was left in 15 patients (18.7%), exceeding 10 mm in 3 patients. Acute neurotoxicity and skin reactions were mild, the rate of infections was low in both treatment arms. However, myelotoxicity resulted in interruptions of radiotherapy in 31.9% after intensive chemotherapy as compared to 20.0% without preceding chemotherapy. CONCLUSIONS: In the HIT '91 trial a precise radiotherapy of craniospinal axis has been performed in the majority of patients. Our findings indicate that the high quality is possibly an important contributing factor for the therapeutic outcome. However, preceding intensive chemotherapy caused marked toxicity of subsequent irradiation leading to a high rate of interruptions. Our database is subject to a future analysis of recurrences.

Brain Neoplasms↗
PubMed1999

[Combined radiochemotherapy of non-small-cell bronchial carcinoma with taxol].

BACKGROUND: In the last few years platin-based radiochemotherapy has become standard treatment for patients with advanced, surgically unresectable non-small-cell lung cancer (NSCLC). More recently new chemotherapeutic agents have shown superior activity. Among them paclitaxel (Taxol) is one of the most extensively investigated. RADIOTHERAPY: Despite of promising initial results, locally uncontrolled tumor and distant metastases continue to be the most serious problem of this disease. Improvement of local control can be achieved by escalating radiation dose, by shortening of treatment time with accelerated fractionation or by additional use of radiosensitizing agents. Concerning local control a tumor volume-dose relationship has been described. Three-dimensional conformal treatment planning eventually with intensity modulated fields, combined with biological TCP/NTCP calculation models allows risk-adapted escalation and intensification of irradiation. TAXOL: A radiosensitizing effect of Taxol by means of G2/M block has been reported. However, radiobiological data are contradictory and suggest a radiosensitizing effect even without cell-cycle arrest. For simultaneous paclitaxel and 60 Gy normally fractionated radiotherapy several prospective dose escalation studies have confirmed a maximum weekly Taxol dose of 60 mg/m2. Changes in paclitaxel application (e.g. daily, twice weekly or biweekly) or in radiotherapy fractionation require a corresponding adaption of Taxol dose. Dose limiting toxicity of this simultaneous treatment is esophagitis. With respect to the high rate of distant metastases sequential application of combined chemotherapeutic regimens (e.g. Taxol 200 mg/m2/Carboplat AUC 6) is generally recommended.

Carcinoma, Bronchogenic↗