Biomedical subjects

Volker Budach

Publications and source records attributed to Volker Budach.

At least 19 recordsLinked to original sources

PubMed2006

Radiochemotherapy combined with regional pelvic hyperthermia induces high response and resectability rates in patients with nonresectable cervical cancer > or =FIGO IIB "bulky".

PURPOSE: To evaluate preoperative radiochemotherapy combined with regional pelvic hyperthermia in patients with nonresectable cervical cancer >/= International Federation of Gynecology and Obstetrics (FIGO) IIB "bulky" in a Phase II study. METHODS AND MATERIALS: Thirty-two patients with nonresectable FIGO IIB-IVA cervical cancer confined to the pelvis were treated with radiochemotherapy (5 x 1.8 Gy/wk, 45-50.4 Gy; cisplatin, 40 mg/m2/wk) and weekly regional pelvic hyperthermia (SIGMA-60 applicator, system BSD-2000; BSD Medical Corp., Salt Lake City, UT). Responders underwent hysterectomy if possible, whereas patients still unresectable received definitive hyperthermic radiochemotherapy. Feasibility, toxicity, as well as response and resectability, local progression free- and overall survival rates, were evaluated. RESULTS: Thirty of 32 patients completed treatment. Grade III/IV toxicities (National Cancer Institute-Common Toxicity Criteria) were diarrhea (n = 5), weight loss >10 kg (n = 4), and nausea (n = 2). Twenty-four of 32 patients (75%) achieved a partial remission after 45-50 Gy, and 20 patients underwent hysterectomy (18 patients, R0; 8 patients pCR). Three-year overall survival was 60%, with moderate (13%) rates of severe late toxicity. R0-resected patients had a favorable chronic toxicity profile and an excellent prognosis (3-year survival rate: 93%). Response depended on thermal parameters (vaginal reference point), whereas response, R0-resection, and FIGO stage are significant prognostic factors for survival. CONCLUSION: Preoperative hyperthermic radiochemotherapy (45-50 Gy) induces high response rates and enables curative surgery in a high proportion of patients with nonresectable cervical cancer. Therefore, the use of hyperthermia in conjunction with standard chemo-/radiotherapy +/- surgery may allow for more effective tumor treatment while decreasing the risk of complications in patients with locally advanced cervical cancer.

Adult↗

PubMed2006

Noninvasive magnetic resonance thermography of soft tissue sarcomas during regional hyperthermia: correlation with response and direct thermometry.

BACKGROUND: The objective of this study was to evaluate noninvasive magnetic resonance (MR) thermography for the monitoring of regional hyperthermia (RHT) in patients with soft tissue sarcomas of the lower extremities and pelvis. METHODS: Noninvasive MR monitoring during RHT was performed in 9 patients who had high-risk soft tissue sarcomas of the lower extremities or pelvis during neoadjuvant chemotherapy plus RHT in the scope of the European Organization for Research and Treatment of Cancer 62961/European Society for Hyperthermic Oncology RHT-95 study. Anatomic and temperature-sensitive data sets were acquired every 10 minutes before and during RHT (using gradient-echo-sequences with variable echo times). MR temperature distributions were derived from the phase differences by using the proton-resonance frequency shift method. A phase convolution setting phase shifts to zero in the fat tissue was performed as a drift correction. The mean MR temperatures in the tumor and muscles and the index temperatures (e.g., T90, which covers 90% of the target volume) and thermal doses were determined and compared with pathohistologic responses and direct temperature measurements if available. RESULTS: Thirty of 72 MR-thermography data sets (>40% of heat sessions) were evaluable. A significant correlation was observed between pathohistologic response (defined as a necrosis rate >or=90%) and standardized thermal parameters, such as thermal dose cumulative equivalent minutes at 43 degrees C to 90% of the target volume (T90) (P = .050), mean T90 (P = .048), or T50 (P = .050). The correlation of 13 conventional temperature measurements performed in selected patients and sessions invasively in the tumor or noninvasively in rectum and bladder revealed an excellent correlation with MR temperatures (R2 = .96). CONCLUSIONS: Noninvasive MR thermography of soft tissue sarcoma was feasible and suitable for validating the quality of heating during RHT.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2006

A non-randomised, single-centre comparison of induction chemotherapy followed by radiochemotherapy versus concomitant chemotherapy with hyperfractionated radiotherapy in inoperable head and neck carcinomas.

BACKGROUND: The application of induction chemotherapy failed to provide a consistent benefit for local control in primary treatment of advanced head and neck (H&N) cancers. The aim of this study was to compare the results of concomitant application of radiochemotherapy for treating locally advanced head-and-neck carcinoma in comparison with the former standard of sequential radiochemotherapy. METHODS: Between 1987 and 1995 we treated 122 patients with unresectable (stage IV head and neck) cancer by two different protocols. The sequential protocol (SEQ; 1987-1992) started with two courses of neoadjuvant chemotherapy (cisplatin [CDDP] + 120-h continuous infusions (c.i.) of folinic acid [FA] and 5-fluorouracil [5-FU]), followed by a course of radiochemotherapy using conventional fractionation up to 70 Gy. The concomitant protocol (CON; since 1993) combined two courses of FA/5-FU c.i. plus mitomycin (MMC) concomitantly with a course of radiotherapy up to 30 Gy in conventional fractionation, followed by a hyperfractionated course up to 72 Gy. Results from the two groups were compared. RESULTS: Patient and tumor characteristics were balanced (SEQ = 70, CON = 52 pts.). Mean radiation dose achieved (65.3 Gy vs. 71.6 Gy, p = 0.00), response rates (67 vs. 90 % for primary, p = 0.02), and local control (LC; 17.6% vs. 41%, p = 0.03), were significantly lower in the SEQ group, revealing a trend towards lower disease-specific (DSS; 19.8% vs. 31.4%, p = 0.08) and overall (14.7% vs. 23.7%, p = 0.11) survival rates after 5 years. Mucositis grades III and IV prevailed in the CON group (54% versus 44%). Late toxicity was similar in both groups. CONCLUSION: Concurrent chemotherapy seemed more effective in treating head and neck tumors than induction chemotherapy followed by chemoradiation, resulting in better local control and a trend towards improved survival.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2006

Influence of organ at risk definition on rectal dose-volume histograms in patients with prostate cancer undergoing external-beam radiotherapy.

PURPOSE: To evaluate rectal dose-volume relations during three-dimensional conformal radiotherapy of patients with prostate cancer by means of different rectal volume contours. PATIENTS AND METHODS: 55 patients with prostate cancer underwent three-dimensional conformal external-beam radiotherapy. Rectal dose-volume histograms were calculated for four separately contoured rectal volumes in all patients resulting in four groups. In group 1 the outer rectal wall was contoured two CT slices above and below the planning target volume. The rectal contour of group 2 was drawn from the anal verge up to the sigmoid. Furthermore, the posterior half of the rectum was contoured for both volumes mentioned above (groups 1a and 2a). Statistical analysis was then performed using nonparametric Wilcoxon tests. RESULTS: The mean target dose was 72.9 Gy (standard deviation [SD] +/- 2.1 Gy). The minimum target dose was 70.2 Gy. Mean rectum dose (+/- SD) over all patients was 50.7 Gy (+/- 4.6 Gy), 45.2 Gy (+/- 5.4 Gy), 43.2 Gy (+/- 4.2 Gy), and 38.7 Gy (+/- 5.5 Gy) for group 1, 2, 1a, and 2a, respectively. The corresponding volumes receiving > or = 70 Gy for groups 1 and 2 were 14.0% (+/- 5.3%) and 11.9% (+/- 4.5%). These differences were statistically significant. Comparison of minimum and mean rectal dose also revealed a statistically significant difference toward higher doses in groups 1 and 1a (p < 0.001). Maximum rectal doses for groups 1 and 2 as well as for groups 1a and 2a revealed no statistically significant difference (p = 1.0). CONCLUSION: Data from the literature on normal-tissue complication probability (rectal bleeding) refer to different rectal contours. When applying dose restrictions to the rectum, contouring becomes a significant factor that determines the risk of rectal toxicity. The results of this study show that different ways of rectal contouring significantly influence doses to the rectum. The influence of organ at risk contouring should be considered thoroughly in conformal radiotherapy of prostate cancer patients, especially in dose escalation studies. It is recommended to calculate the doses for absolute rectal volumes and correlate these data with toxicity in order to be able to achieve comparable results among different institutions.

Data Interpretation, Statistical↗

PubMed2006

Temozolomide with or without radiotherapy in melanoma with unresectable brain metastases.

Brain metastases are a common complication in patients suffering from metastatic malignant melanoma. We analyzed efficacy and toxicity of the alkylating agent temozolomide with excellent CNS penetration and known activity in brain metastasis in 35 patients with unresectable melanoma brain metastases. Patients received 200 mg/m2 temozolomide on days 1 to 5 every 28 days as first or second-line therapy. This therapy regimen was combined with radiotherapy of the brain metastases in 22/35 patients. Grade III and IV toxicity was observed in 8/35 patients (leukopenia, granulocytopenia, thrombocytopenia, anemia, nausea and obstipation). Complete remission was observed in 1/34, partial remission in 2/34 and stable disease in 9/34 patients. In 5/34 a mixed response was assessed, 17/34 had disease progression and in one patient tumor response was not evaluable. The median progression free time was 5 (0-8) months for all patients, the median survival time for all patients from start of therapy was 8 (0-28) months, 9 (2-28) months in patients with concurrent stereotactic radiotherapy and 7 (3-17) months in patients with concurrent whole brain radiotherapy. Our results demonstrate that temozolomide can be combined with radiotherapy for the treatment of brain metastases in malignant melanoma, and that this combination may prolong survival in this patient group.

Antineoplastic Agents, Alkylating↗

PubMed2005

Hyperfractionated accelerated chemoradiation with concurrent fluorouracil-mitomycin is more effective than dose-escalated hyperfractionated accelerated radiation therapy alone in locally advanced head and neck cancer: final results of the radiotherapy cooperative clinical trials group of the German Cancer Society 95-06 Prospective Randomized Trial.

PURPOSE: To report the results and corresponding acute and late reactions of a prospective, randomized, clinical study in locally advanced head and neck cancer comparing concurrent fluorouracil (FU) and mitomycin (MMC) chemotherapy and hyperfractionated accelerated radiation therapy (C-HART; 70.6 Gy) to hyperfractionated accelerated radiation therapy alone (HART; 77.6 Gy). PATIENTS AND METHODS: Three hundred eighty-four stage III (6%) and IV (94%) oropharyngeal (59.4%), hypopharyngeal (32.3%), and oral cavity (8.3%) cancer patients were randomly assigned to receive either 30 Gy (2 Gy every day) followed by 1.4 Gy bid to a total of 70.6 Gy concurrently with FU (600 mg/m(2), 120 hours continuous infusion) days 1 through 5 and MMC (10 mg/m(2)) on days 5 and 36 (C-HART) or 14 Gy (2 Gy every day) followed by 1.4 Gy bid to a total dose of 77.6 Gy (HART). The data were analyzed on an intent-to-treat basis. RESULTS: At 5 years, the locoregional control and overall survival rates were 49.9% and 28.6% for C-HART versus 37.4% and 23.7% for HART, respectively (P = .001 and P = .023, respectively). Progression-free and freedom from metastases rates were 29.3% and 51.9% for C-HART versus 26.6% and 54.7% for HART, respectively (P = .009 and P = .575, respectively). For C-HART, maximum acute reactions of mucositis, moist desquamation, and erythema were lower than with HART, whereas no differences in late reactions and overall rates of secondary neoplasms were observed. CONCLUSION: C-HART (70.6 Gy) is superior to dose-escalated HART (77.6 Gy) with comparable or less acute reactions and equivalent late reactions, indicating an improvement of the therapeutic ratio.

Actuarial Analysis↗

PubMed2005

High dose rate (HDR) brachytherapy with conformal radiation therapy for localized prostate cancer.

OBJECTIVES: To evaluate the outcome of high dose rate (HDR) brachytherapy with iridium 192 (Ir(192)) and 3D conformal external beam radiotherapy in patients with localized prostate cancer. METHODS: A total of 442 patients with localized prostate cancer underwent combined radiotherapy with interstitial brachytherapy with Ir(192) and 3D conformal external beam radiotherapy between December 1992 and March 2001. Patients underwent laparoscopic pelvic lymph node dissection to exclude patients with lymphatic involvement. Iridium 192 was delivered twice with a one-week interval in afterloading technique. 247 patients (56%) had clinical T3 disease and 128 patients (29%) had an initial PSA of more than 20 ng/ml. Progression was defined as biochemical failure according to ASTRO criteria. Patients were divided according to pretreatment variables that independently affected prostate-specific antigen (PSA) relapse-free survival in three risk groups. Low risk was defined as cT1c-cT2 and G1-G2 and PSA<10 ng/ml (n=94). Intermediate risk included patients with cT1c-cT2 and G1-G2 and PSA between 10 and 20 ng/ml (n=53). High risk group patients were cT3 or G3 or PSA>20 ng/ml (n=295). RESULTS: Median follow-up was 5 years. Late grade 3-4 complications according to RTOG/EORTC criteria occurred in 50 patients (11%). The initial PSA value decreased from median 11.8 ng/ml to 0.98 ng/ml 12 months after treatment, to 0.3 ng/ml after 60 months and to 0.1 ng/ml 10 years after therapy. 53% of the patients (n=235) reached a PSA nadir of 0.5 ng/ml. 66 patients (15%) had a local recurrence, 54 (12%) developed systemic disease and 12 (3%) had both local and systemic failure. The progression free survival rate was 65% at 5-year follow-up. Five-year progression free survival was 81% in the low risk group, 65% in the intermediate risk group and 59% in the high risk group. Five-year overall survival was 87% and 5-year disease specific survival 94%. Initial PSA value, risk group and age were significantly related to progression free survival. CONCLUSIONS: Combined HDR brachytherapy with Iridium 192 is an alternative treatment option for patients with localized prostate cancer. Initial PSA value, risk group, and age are important prognostic factors for progression free survival.

Aged↗

PubMed2005

Testicular dose in prostate cancer radiotherapy: impact on impairment of fertility and hormonal function.

PURPOSE: To determine the dose received by the unshielded testicles during a course of 20-MV conventional external-beam radiotherapy for patients with localized prostate cancer. Critical evaluation of the potential impact on fertility and hormonal impairment in these patients according to the literature. PATIENTS AND METHODS: The absolute dose received by the testicles of 20 randomly selected patients undergoing radiotherapy of prostate cancer was measured by on-line thermoluminescence dosimetry. Patients were treated in supine position with an immobilization cushion under their knees. A flexible tube, containing three calibrated thermoluminescence dosimeters (TLDs) was placed on top or underneath the testicle closest to the perineal region with a day-to-day alternation. The single dose to the planning target volume was 1.8 Gy. Ten subsequent testicle measurements were performed on each patient. The individual TLDs were then read out and the total absorbed dose was calculated. RESULTS: The mean total dose (+/- standard deviation) measured in a series of 10 subsequent treatment days in all patients was 49 cGy (+/- 36 cGy). The calculated projected doses made on a standard series of 40 fractions of external-beam radiotherapy were 196 cGy (+/- 145 cGy). The results of this study are appraised with the available data in the literature. CONCLUSION: The dose received by the unshielded testes can be assessed as a risk for permanent infertility and impairment of hormonal function in prostate cancer patients treated with external-beam radiotherapy.

Aged↗

PubMed2005

Regional hyperthermia in conjunction with definitive radiotherapy against recurrent or locally advanced prostate cancer T3 pN0 M0.

BACKGROUND AND PURPOSE: Since long-term results of the standard treatment of locally advanced or recurrent prostatic carcinoma are unsatisfactory, the role for additional regional hyperthermia was evaluated in a phase I/II study. PATIENTS AND METHODS: From 08/1996 to 03/2000, 22 patients were treated by a standard irradiation regimen (68.4 Gy) in combination with regional hyperthermia (weekly, five to six times), and five of 22 patients received short-term (neoadjuvant) hormonal treatment. Of these, 15 patients had primary prostatic carcinoma T3 pN0 M0 and seven a histologically confirmed local recurrence after radical prostatectomy. Feasibility of hyperthermia, and acute/late toxicity as well as long-term follow-up (prostate- specific antigen [PSA] control, overall survival) were analyzed. Clinical endpoints were correlated with thermal parameters. RESULTS: Mean maximum temperatures along the urethra of 41.4 degrees C (41.0 degrees C for the recurrences), and mean T(90) values of 40.7 degrees C could be achieved. Severe acute toxicity of grade 3 occurred at the rectum in three, at the urethra in four, at the intestine in one, and a burn induced by hyperthermia in one of 22 patients. Late toxicity was only observed rectally in one patient (grade 3) and at the urethra in two patients (grade 2). There was no correlation between thermal parameters and any toxicity. The survival curves showed a PSA control for primary prostatic carcinoma > 50% after 6 years, but no long-term PSA control for the recurrences. Overall survival after 6 years was 95% for primary carcinoma, and 60% for the recurrences. There was a clear correlation between higher temperatures or thermal doses with long-term PSA control. CONCLUSION: Regional hyperthermia might be a low-toxicity approach to increase PSA control of common treatment schedules. Further evaluation, in particular employing improved hyperthermia technology, is worthwhile.

Aged↗

PubMed2004

Virtual simulation of a boost field in adjuvant radiotherapy of the breast.

BACKGROUND AND PURPOSE: In CT-based adjuvant radiotherapy of the breast, virtual simulation techniques have been developed. This paper demonstrates a simple virtual simulation of a boost field. MATERIAL AND METHODS: 41 fields were planned virtually, 26 as electron beams, 15 as tangential photon beams. RESULTS: Depending on the user's expertise the geometric accuracy was high; possible sources of error are illustrated. Resulting field sizes tended to be slightly larger compared to conventional simulation when applying the same rules of field definition. Differences in focus-skin distances with consecutive divergence effects as well as partial volume effects were discussed to be causal. CONCLUSION: Virtual simulation of a boost field has the potential to elegantly link the simplicity of a conventional simulation with the accurate tumor bed identification provided by a CT data set. It was shown to be feasible and favorable with regard to the patient, the medical staff, and the simulator time. Moreover, it offers a visualization of dose distributions, which was found helpful in some cases.

Breast Neoplasms↗

PubMed2004

Thermoradiotherapy using interstitial self-regulating thermoseeds: an intermediate analysis of a phase II trial.

OBJECTIVE: Thermoradiotherapy in the treatment of prostate cancer is based on a variety of experimental and clinical phase I data which have proven the synergistic effects of this combination. We report on a phase II trial in a special hyperthermia research group (SFB 273) of the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) to determine feasibility, acute toxicity and efficacy of this combination for prostate cancer. METHODS: 57 patients with localized prostate cancer were treated with interstitial hyperthermia using cobalt-palladium thermoseeds and conformal radiation between July 1997 and December 2000. Thermoseeds were placed into the prostate homogeneously. Hyperthermia was created using a magnetic field and was delivered in six sessions once weekly for one hour. 3D-conformal radiotherapy of 68.4Gy was given simultaneously in daily fractions of 1.8Gy. RESULTS: Intraprostatic temperatures were between 42 and 46 degrees C. No major side effects were observed during hyperthermia. Median follow-up was 36 months (range 3-72 months). Median PSA value decreased from 11.6ng/ml to 2.4ng/ml 3 months after treatment, to 1.3ng/ml 12 months after treatment and to 0.55ng/ml 2 years after therapy. CONCLUSION: Interstitial hyperthermia is feasible, well tolerated and led to a steep decrease of PSA values. Combining effective interstitial hyperthermia with conformal radiotherapy may be an exciting innovative treatment option for prostate cancer.

Aged↗

PubMed2004

Literature-based recommendations for treatment planning and execution in high-dose radiotherapy for lung cancer.

BACKGROUND AND PURPOSE: To review the literature on techniques used in high-dose radiotherapy of lung cancer in order to develop recommendations for clinical practice and for use in research protocols. PATIENTS AND METHODS: A literature search was performed for articles and abstracts that were considered both clinically relevant and practical to use. The relevant information was arbitrarily categorized under the following headings: patient positioning, CT scanning, incorporating tumour mobility, definition of target volumes, radiotherapy planning, treatment delivery, and scoring of response and toxicity. RESULTS: Recommendations were made for each of the above steps from the published literature. Although most of the recommended techniques have yet to be evaluated in multicenter clinical trials, their use in high-dose radiotherapy to the thorax appears to be rational on the basis of current evidence. CONCLUSIONS: Recommendations for the clinical implementation of high-dose conformal radiotherapy for lung tumours were identified in the literature. Procedures that are still considered to be investigational were also highlighted.

Dose-Response Relationship, Radiation↗

PubMed2004

Clinical and physical quality assurance for intensity modulated radiotherapy of prostate cancer.

The implementation of intensity modulated radiotherapy (IMRT) for patients with prostate cancer in daily routine has been elaborated at our department. Our quality assurance (QA) concept is one method to pave the way for initiating IMRT treatments for starting institutions. A clinical quality assurance (CQA) procedure has been set-up for all patients before and throughout the course of radiotherapy. Simultaneously medical physicists established a physical quality assurance (PQA) concept that has been followed for all patients as well. Alternative CQA and PQA procedures are discussed. The literature is reviewed and discussed with special respect to quality assurance in IMRT of prostate cancer patients.

Aged↗

PubMed2004

Clinical and physical determinants for toxicity of 125-I seed prostate brachytherapy.

BACKGROUND AND PURPOSE: To assess acute as well as long-term toxicity after permanent prostate seed implantation. To find predictive clinical or dosimetric factors for side effects in order to work out strategies for improvement. PATIENTS AND METHODS: A group of 174 patients with localised prostate cancer was treated with permanent seed implantation between 1999 and 2001, either alone (140 patients) or in combination with external radiotherapy (34 patients). For the majority (114/174, i.e. 66%) a CT was performed four weeks after implantation and analysed in the planning system VariSeed. In the postimplant analysis, dosimetric descriptors (doses, volumes) were determined for the prostate and rectum and compared with the intraoperative values. In addition, a questionnaire was sent to all patients to assess and quantify acute and chronic toxicity (urinary, rectal, sexual) and the impact on subjective acceptance and quality of life (return rate of questionnaires 83%). The derived score changes were correlated with clinical and dosimetric factors. RESULTS: In the mono-brachytherapy group 14% (16/140) required a bladder catheter, of them 8% (9/140) with a manifest urinary obstruction. Long-term rectal toxicity (<5%) and impairment of potency (<30%) are moderate and obviously below other treatment options. Urinary toxicity is dominant with an overall long-term dysuria up to 30% (at a mean observation interval of ten months), and a significant trend to decline with follow-up time. Conversely, the erectile function tends to deteriorate with follow-up time. Nevertheless, quality of life is not significantly reduced and acceptance is high. Our analysis suggests that the main factor for urinary toxicity and impaired erectile function is the dose load to larger portions of the prostate (D(50)>240 Gy), which appears to be attributed to unnecessarily high numbers of seeds (for a fixed activity per seed) and needles. The rectal toxicity is correlated with the high dose regions in the rectum (>/=145 Gy). Urinary toxicity is lower for combined-brachytherapy, while rectal toxicity and impairment of potency are slightly higher. CONCLUSIONS: Toxicity spectrum and quality of life after permanent seed implantation for early prostate cancer are acceptable for nearly all patients (98%). To further improve tolerance we should attempt to achieve a better dose homogeneity, i.e. by reducing D(50). Therefore, special attention should be given to D(50) during the real-time planning process. The necessity of more homogeneous dose distributions might imply a reduction of the activity per seed, e.g. from 0.7 mCi down to 0.6 mCi.

Aged↗

PubMed2003

Multigene analysis of Rb pathway and apoptosis control in esophageal squamous cell carcinoma identifies patients with good prognosis.

Deregulation of cell-cycle G(1)-restriction point control by disruption of Rb-pathway components is a frequent event in cancer. In concert with the inactivation of cell death pathways, such events not only contribute to tumor development but also determine the intrinsic and acquired resistance to cancer therapy and, ultimately, disease prognosis. We previously observed that the cyclin-dependent kinase inhibitor p16(INK4a) and the proapoptotic Bcl-2 homolog Bax are positive prognostic factors and identify patients with good prognosis in esophageal squamous cell carcinoma (SCC). In the present study, we therefore extend our analysis to additional genes controlling the G(1) restriction point and apoptosis, respectively. This retrospective analysis was performed in a cohort of 53 patients undergoing surgery for esophageal SCC with curative intent, i.e., R0 resection. Protein expression profiles of cyclin D1, p16(INK4a), Rb, p21(CIP/WAF-1), p53, Bax and Bcl-2 were analyzed by immunohistochemistry and compared to p53 mutational status, as determined by SSCP-PCR of exons 5-8. Loss of p16(INK4a), Rb, p21(CIP/WAF-1) or Bax and overexpression of cyclin D1 were associated individually with shorter overall survival, while Bcl-2 expression and p53 mutation were not of prognostic relevance. The longest survival was observed in a subgroup of patients whose tumors bore a combination of favorite genotypes, i.e., low cyclin D1 and high Rb, p21(CIP/WAF-1), p16(INK4a) and Bax protein expression. These results show that multigene analyses based on limited sets of functionally linked genes reliably identify patients with good vs. poor prognosis.

Adult↗

PubMed2003

CT-based delineation of lymph node levels and related CTVs in the node-negative neck: DAHANCA, EORTC, GORTEC, NCIC,RTOG consensus guidelines.

BACKGROUND AND PURPOSE: The appropriate application of 3-D CRT and IMRT for HNSCC requires a standardization of the procedures for the delineation of the target volumes. Over the past few years, two proposals--the so-called Brussels guidelines from Grégoire et al., and the so-called Rotterdam guidelines from Nowak et al.--emerged from the literature for the delineation of the neck node levels. Detailed examination of these proposals however revealed some important discrepancies. MATERIALS AND METHODS: Within this framework, the Brussels and Rotterdam groups decided to review their guidelines and derive a common set of recommendations for delineation of neck node levels. This proposal was then discussed with representatives of major cooperative groups in Europe (DAHANCA, EORTC, GORTEC) and in North America (NCIC, RTOG), which, after some additional refinements, have endorsed them. The objective of the present article is to present the consensus guidelines for the delineation of the node levels in the node-negative neck. RESULTS AND CONCLUSIONS: First a short discussion of the discrepancies between the previous Brussels and the Rotterdam guidelines is presented. The general philosophy of the consensus guidelines and the methodology used to resolve the various discrepancies are then described. The consensus proposal is then presented and representative CTVs that are consistent with these guidelines are illustrated on CT sections. Last, the limitations of the consensus guidelines are discussed and some concerns about the direct applications of these guidelines to the node-positive neck and the post-operative neck are described.

Head and Neck Neoplasms↗

PubMed2003

CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment.

Multiple systems have been developed for grading the adverse effects (AEs) of cancer treatment. The National Cancer Institute Common Toxicity Criteria (CTC) system has substantially evolved since its inception in 1983. The most recent version, CTCAE v3.0 (Common Terminology Criteria for Adverse Events version 3.0) represents the first comprehensive, multimodality grading system for reporting the acute and late effects of cancer treatment. The new CTC requires changes in the application of AE criteria including new guidelines regarding late effects, surgical and pediatric effects, multimodality issues, and for reporting the duration of an effect. It builds on the strengths of previous systems, represents a considerable effort among hundreds of participants, and signifies an international collaboration and consensus of the oncology research community. This article updates recent progress in the evolution of adverse effects grading systems and reviews the development of CTCAE v3.0.

Academies and Institutes↗

PubMed2003

Increased radiation-induced apoptosis and altered cell cycle progression of human lung cancer cell lines by antisense oligodeoxynucleotides targeting p53 and p21(WAF1/CIP1).

Lung cancer is difficult to control locally by radiotherapy and is known to have frequently p53 mutations. Previous results have shown that non-small-cell lung cancer (NSCLC) cell lines with nonfunctional p53 have a higher fraction of radiation-induced apoptosis and that apoptosis follows after the release from the G2/M arrest. The aim of the present work was to study whether inhibition of the p53 response in NSCLC cell lines can modulate the G2/M arrest and the induction of apoptosis after ionizing radiation. Antisense oligodeoxynucleotides (As-ODNs) were used to inhibit the p53 response in the cell lines H460 and A549 with functional p53. In addition, H661 with nonfunctional p53 was used. The results have shown that As-ODNs targeting mRNA of p53 and p21 downregulate radiation-induced expression of p53 and p21(WAF1/CIP1). Delayed apoptosis (35.7+/-4.2% in H460, 1.2+/-0.4% in A549 and 72.2+/-6.5% in H661) was observed after cell cycle progression beyond the G2 block, either in the late G2 phase of the same cell cycle being irradiated (H661) or in the G1 phase of the subsequent cell cycle (H460, A549). As-p53 significantly decreased the fraction of G2/M-arrested cells in H460 cells and increased radiation-induced apoptosis at 96 hours by 17.9+/-8.5 and 9.1+/-3.3% to 53.6+/-7.4 and 10.8+/-2.9% in H460 and A549 cells (P<.01), respectively, but had no effect in H661 cells with nonfunctional p53. In addition, As-p21 decreased the fraction of G2-arrested A549 and H460 cells and increased apoptosis by 23.8+/-5.2 and 31.6+/-7.3% to 59.4+/-3.1 and 32.8+/-7.3%, respectively (P<.01). In conclusion, these data show that radiation-induced G2 arrest is decreased in NSCLC cells and radiation-induced apoptosis is increased when p53-responsive pathways are blocked via As-ODN targeting p53 or p21(WAF1/CIP1) mRNA. In view of the fact that p53 and p21 As-ODN had similar effects on radiation-induced apoptosis normalized by their ability to inhibit radiation-induced p21 expression, we concluded that p21 is an important trigger of late ionizing radiation-induced apoptosis.

Apoptosis↗