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Biomedical subjects

Michael Bamberg

Publications and source records attributed to Michael Bamberg.

At least 37 records · Page 2Linked to original sources

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↗

Meeting report: primary central nervous system lymphoma: standards of care and future perspectives.

A standard of care for patients with primary central nervous system lymphoma (PCNSL) has not been defined. Current controversies concern, amongst others, the role, dose and timing of radiotherapy, the role of intrathecal chemotherapy and the delineation of age-specific standards of care. Given the strong clinical trial activities for PCNSL in Germany, the PCNSL conference held in Tubingen aimed at comparing the diverging trial strategies in Germany and at exploring the options for joint activities of the various PCNSL study groups in the near future.

Antineoplastic Agents↗

NOA-03 trial of high-dose methotrexate in primary central nervous system lymphoma: final report.

The NOA-03 trial explored high-dose methotrexate alone in 37 patients with primary central nervous system lymphoma. The overall median survival was 25 months. After 4 years, the rate of leukoencephalopathy in patients surviving more than 12 months was 58% with and 10% without whole-brain radiotherapy given at relapse (p = 0.11). Attention deficits were found in all six tested patients, and memory deficits in four patients. Two patients had normal, three had moderately restricted, and one had markedly restricted quality of life. Thus, high-dose methotrexate with deferred radiotherapy had only moderate efficacy and was associated with significant neurotoxicity in long-term surviving patients.

Antimetabolites, Antineoplastic↗

Primary central nervous system lymphomas (PCNSL): MRI features at presentation in 100 patients.

To avoid an unnecessary extend of surgery in primary central nervous system lymphoma (PCNSL), the diagnosis should be suspected after MRI. Pre-treatment MRI examinations of 100 immunologically competent patients with biopsy-proven PCNSL were evaluated. All patients had T2- and T1-weighted images with contrast enhancement. Diffusion-weighted MRI (DW-MRI) was available in 15, proton-MR-spectroscopy (1H-MRS) in four patients. The number of lesions ranged from one (n=65 patients) to eight (n=1) with a mean of 1.7. The most frequent locations were the cerebral hemispheres (n=66), the basal ganglia (n=27) and the corpus callosum (n=24). In the 65 patients with a solitary lesion, hemispheric lesions were most frequent (n=23) followed by corpus callosum (n=18). Contrast enhancement was found in all but one patient. 1H-MRS revealed a uniformly pathologic pattern of metabolite concentrations in all patients. Characteristic imaging features of PCNSL are contrast-enhancing lesions with a diameter of at least 15 mm in contact with the subarachnoid space. DW-MRI and proton spectroscopy may aid in differential diagnosis.

Adult↗

Clinical quality assurance for 106Ru ophthalmic applicators.

BACKGROUND AND PURPOSE: Episcleral brachytherapy using 106Ru/106Rh ophthalmic applicators is a proven method of therapy of uveal melanomas sparing the globe and in many cases sparing the vision. In the year 2001, an internal clinical quality assurance procedure revealed that part of the ophthalmic applicators leaked and that the calibration was erroneous. Consequently, the producer modernized its production procedures and, in May 2002, introduced a dose rate calibration that is traceable to the NIST standard. This NIST calibration confirmed that the previous calibration had been incorrect. In order to study the effects of the producer's new internal quality assurance procedures on the ophthalmic applicators, applicators of this new generation were submitted to a newly improved internal clinical acceptance test. PATIENTS AND METHODS: The internal clinical acceptance test consists of a leakage test and a dosimetric test of the ophthalmic applicators. The leakage test simulates contact of the ophthalmic applicators with chloride containing body fluid. The dosimetric tests measure depth dose curves and dose rate with a plastic scintillator dosimetric system and compare them with the indications in the producer's certificate. Furthermore, the depth dose profile of the most frequently used applicator (type CCB) was compared with published data. RESULTS: The internal clinical leakage test showed that all of the tested ophthalmic applicators belonging to the new generation (n=17) were tight and not contaminated. The dosimetric acceptance tests applied to seven different types of applicators revealed that the relative depth dose profiles in the therapeutically relevant range (up to a depth of <or=7 mm) deviate from the producer's indications only by -2.7 to +3.2%. The acceptance test of the dose rate values of the ophthalmic applicators at a distance of 2mm from the surface of the applicators resulted in a coefficient of variation of 1.7% (n=17). In the evaluation of the depth dose profile of the type CCB applicator the producer's indications and the results of the entrance test conformed very well to published data. CONCLUSIONS: The internal clinical quality assurance procedure has proved successful in three ways. (1) It had a catalytic effect that led to the development of a new generation of ophthalmic applicators. (2) It could be demonstrated that this new generation of applicators is up to the state of the art in brachytherapy. (3) With this new generation of 106Ru/106Rh ophthalmic applicators it is possible for the first time in the history of their use to apply the dose that is prescribed by the radiooncologist.

Brachytherapy↗

Leptomeningeal metastasis: survival and prognostic factors in 155 patients.

In this single-center retrospective study, 155 consecutive patients with leptomeningeal metastasis (LM) were analyzed for the prognostic role of patient- and therapy-related variables. Ten percent of the patients received radiotherapy alone, 32% had chemotherapy alone, 31% received radiochemotherapy, 17% had supportive therapy only, and 10% were not evaluable for therapy. Chemotherapy was systemic (17%), combined systemic and intrathecal (10%), or intrathecal only (35%). Clinical improvement was noted in 41% of the patients. Overall median survival time (MST) was 4.8 months. Survival varied considerably depending on the type of primary tumor in this largest published cohort of LM patients. Univariate Cox regression analysis revealed that age >60 and elevated cerebrospinal fluid (CSF) albumin or lactate levels were therapy-independent predictors of poor survival in the entire cohort as well as in the subgroup of patients with systemic primary tumors (n=105). The assessment of three therapy-independent parameters allows to group LM patients into groups of low, intermediate, and high risk of poor survival. Moreover, the application of systemic chemotherapy was a positive prognostic factor in patients with subarachnoid lesions detected by neuroimaging (RR 1.94, p=0.001) or with extra-CNS tumor deposits (RR 1.52, p=0.05). The results of this study suggest that systemic chemotherapy alone or in combination with other therapeutic modalities may improve outcome in patients with subarachnoid tumor cell deposits detectable by neuroimaging.

Adolescent↗

Hyperfractionated accelerated radiotherapy alone and with concomitant chemotherapy to the head and neck: treated within and outside of randomized clinical trials.

PURPOSE: A German multicenter randomized trial (ARO 95-6) compared hyperfractionated accelerated radiotherapy (RT) alone (to a total radiation dose of 77.6 Gy) with hyperfractionated accelerated radiochemotherapy (to 70.6 Gy) using concurrent mitomycin C and 5-fluorouracil. We analyzed the baseline patient characteristics and the influence of physician selection bias on treatment outcome for patients who were and were not enrolled in the randomized Phase III trial, with the therapies administered according to the trial protocols. METHODS AND MATERIALS: Between February 1996 and May 2000 at Tübingen University, 42 on-study patients and 41 off-study patients with Stage III-IV nonmetastatic squamous cell carcinoma of the head and neck were treated. The median follow-up for patients at risk (living at last evaluation) was 44 months, with a minimal follow-up of 2 years. RESULTS: The 4-year rate of overall survival, disease-specific survival, and locoregional tumor control was 25%, 40%, and 54%, respectively, for all 83 patients. Among patients enrolled in the study, the 4-year rate of overall survival for those receiving accelerated hyperfractionated radiochemotherapy was 33%, and that for patients receiving accelerated hyperfractionated RT alone was 18% (p = 0.25); among off-study patients, the comparable rates were 48% and 0% (p = 0.004). The 4-year rate of disease-specific survival among on-study patients receiving radiochemotherapy and RT alone was 41% and 36%, respectively (p = 0.5); among off-study patients the respective rates were 58% and 0% (p = 0.2). The rate of 4-year locoregional tumor control associated with radiochemotherapy and RT, respectively, was 51% and 54% among on-study patients and 72% and 23% among off-study patients (p = 0.08). CONCLUSION: Patients with advanced head-and-neck cancer who were entered into the randomized trial did not have statistically significantly different survival than patients treated according to the same protocol but outside the trial. Also, outside the trial, the physicians' selection bias in determining which patient received which treatment showed a much greater benefit from combined modality treatment than that found in the randomized trial.

Adult↗

On the actual state of industrial quality assurance procedures with regard to (106)Ru ophthalmic plaques.

BACKGROUND: In radiotherapy of intraocular tumors, e. g., in the case of malign choroid melanomas, episcleral brachytherapy with (106)Ru ophthalmic plaques has proven to be successful. In a study, the authors reported on the discovery of the following shortcomings in industrial quality assurance, which are relevant to therapy, during the course of an internal clinical acceptance test of (106)Ru ophthalmic plaques, manufactured by the company Bebig from Berlin, Germany. This consisted of inconsistent dose rate specifications in the manufacturer's certificate, covering a range of 111% and with the risk of leakage of the plaques. Bebig was called upon to adapt state-of-the-art production methods with regard to (106)Ru ophthalmic plaques. MATERIAL AND METHODS: In the meantime, Bebig has modernized production of (106)Ru ophthalmic plaques and adopted all the quality assurance procedures proposed by the authors. Moreover, the requested traceability of the calibration of activity and dose rate of the (106)Ru ophthalmic plaques to standards of the federal authorities in charge of measurement procedures has been implemented. RESULTS: In the year 2002, Bebig updated, among other things, the ASMW (GDR) calibration of the dose rate of the (106)Ru ophthalmic plaques from the years 1987-1989 by a calibration of the NIST (USA). The current NIST calibration, together with the new equipment for the measurement of the depth dose curves, led to the consequence that the new NIST 2001 dose rate values show, in the mean, a deviation of 0.75 times (plaque type CCC) up to 2.06 times (plaque types CCX, CCY, and CCZ) compared to the dose rate values that had been indicated so far in Bebig's certificate, based on the ASMW 1987 calibration. For the 95% confidence interval, Bebig estimated the measurement uncertainty to be +/- 25%. If one takes into consideration the minimal and maximal values in such 95% confidence intervals, it follows that the new NIST 2001 dose rate values deviate between 0.56 times (plaque type CCC) and 2.58 times (plaque types CCX, CCY, and CCZ) from the Bebig certificate (ASMW calibration 1987). As regards leakage, no objections arose in the case of the (106)Ru ophthalmic plaques produced according to the new quality standards. CONCLUSION: Legislation has to make sure that the use of radioactive material on humans be, among other things, permitted as a matter of principle only, if the dose rate calibration can be traced to standards of a federal authority of measurement procedures. Furthermore, special leakage tests for radiation sources which come into direct contact with body fluids should be established. A historical retrospect reveals that the greatest changes have taken place in the indication of the dose rates of (125)I sources. Since the beginning of the use of (125)I sources in brachytherapy in the late 1960s, the dose rate indications, so far, have had to be reduced in small steps over a period of about 35 years by nearly a factor of 2. As regards the (106)Ru ophthalmic plaques, the NIST 2001 calibration has resulted in a comparable reduction of the dose rate indications of up to a factor of 2 within the period of about several months. Thus, in the previous history of radiotherapy this case must be regarded as unique, because for the first time ever, an urgently needed recalibration has been protracted for such an unduly long period of time.

Calibration↗

Immediate postoperative radiotherapy or "watch and wait" in the management of adult low-grade glioma?

BACKGROUND: The EORTC Trial 22845 on the role of immediate postoperative radiotherapy in patients with supratentorial lowgrade glioma revealed an advantage of immediate postoperative radiotherapy for progression-free survival, but not for overall survival. It is still an open question in which clinical setting immediate radiotherapy should be considered and whether chemotherapy may become a useful alternative. MATERIAL AND METHODS: Reports in the literature spanning 60 years of radiation therapy were reviewed with respect to timing of radiotherapy, prognostic factors, dose prescriptions, modern treatment techniques, and late effects. Data on chemotherapy were also reviewed. Based on these data, the role of immediate postoperative radiotherapy or chemotherapy in adult low-grade glioma is presented. RESULTS: Radiotherapy is able to control symptoms in up to 80% of cases. Malignant transformation occurs in 36-86% of cases upon progressive disease. Long-term median survival crucially depends on prognostic factors and ranges between 12 months and 10 years. Radiotherapy does not cause neurocognitive deficits, provided that modern treatment techniques and moderate dose prescriptions are used. Recent series with small patient numbers indicate that chemotherapy using PCV or temozolomide may prolong median survival and induces response rates of 50% in oligodendroglial tumors. CONCLUSION: The arguments for immediate postoperative irradiation include: low-grade gliomas respond to radiotherapy; the tumors often display an aggressive pathobiological behavior; patients with high risk profile may benefit from immediate radiotherapy in terms of progression-free and overall survival; modern focal radiotherapy is far less toxic than feared; radiotherapy might be more effective at diagnosis than at progression. Chemotherapy might be an alternative in immediate postoperative treatment. Its role, however, is unclear. The forthcoming prospective trial of the EORTC will address this issue in a randomized setting.

Brain Neoplasms↗

Postmastectomy radiotherapy of the chest wall. Comparison of electron-rotation technique and common tangential photon fields.

BACKGROUND AND PURPOSE: Different radiotherapy techniques are being used for postmastectomy irradiation. A retrospective analysis of patterns of locoregional failure (LRF) after modified radical mastectomy and axillary lymph node dissection followed by locoregional radiotherapy with or without systemic treatment was performed. Main emphasis was focused on the comparison of two postmastectomy radiotherapy techniques. PATIENTS AND METHODS: 287 evaluable patients with locally advanced disease and/or adverse pathologic features (pT3 17% of patients, pT4 35%, multicentricity 25%, pN more than three positive nodes and/or pN1biii 70%, "close margins" 29%, infiltration of pectoral fascia 20%) with or without adjuvant chemo-hormonal treatment were included between 1989 and 2000. Median age was 61 years (range 24-88 years). All patients had modified radical mastectomy and axillary lymphonodectomy level I-II(III) for primary breast cancer. Median total dose of conventionally fractionated radiotherapy to the chest wall was 50 Gy (range 46-56 Gy). A local boost to the tumor bed of 10 Gy was applied in 72 patients. 80% of the patients received supraclavicular and 60% ipsilateral internal mammary lymph node irradiation of 50 Gy. 19% of the patients received adjuvant chemo-hormonal therapy, 38% hormonal therapy, and 27% chemotherapy. The median follow-up of patients at risk was 43 months (average 54 months). RESULTS: The 5-year locoregional tumor control (LRC), LRC first event, disease-free, and overall survival were 85%, 91%, 61%, and 70% (Kaplan-Meier analysis), respectively. Cox regression analysis showed that stage III (relative risk [RR] 1.7), more than three involved axillary lymph nodes (RR 5.1), and infiltration of the pectoral fascia (RR 3.2) increased the risk of locoregional failure, while positive estrogen receptor status (RR 0.3) was associated with a reduced risk. No statistically significant differences in LRC were observed for patients treated either with the electron-rotation technique (LRC 92%) or with the photon-based technique (LRC 89%; p = 0.9). A subgroup analysis of tumors resected with "close margins" showed a higher LRF rate of 25% after electronbeam-rotation irradiation (n = 180) compared to an LRF of 13% with tangential opposed 6-MV photon fields (n = 107; p < 0.05). Large primary tumors of > or = 5 cm developed LRF in 29% of patients treated with electron-beam-rotation irradiation and in 17% of patients with photon-based irradiation (p = 0.1). CONCLUSION: In locally advanced breast cancer, the LRC after postmastectomy irradiation with both techniques is comparable with published data from randomized studies. The tangential opposed photon field technique seems to be beneficial after marginal resection (histopathologic "close margins") of the primary tumor.

Abdomen↗

Neuro-Oncology Working Group 01 trial of nimustine plus teniposide versus nimustine plus cytarabine chemotherapy in addition to involved-field radiotherapy in the first-line treatment of malignant glioma.

PURPOSE: The role of chemotherapy in the primary treatment of malignant glioma remains controversial. The results from the German-Austrian Glioma trial (GAG, 1983 to 1988) demonstrated a survival benefit for chemotherapy using carmustine (BCNU) plus teniposide (VM26) over BCNU alone in addition to radiotherapy in patients with a Karnofsky performance score (KPS) more than 60. The Neuro-Oncology Working Group (NOA) of the German Cancer Society therefore compared the efficacy of nimustine (ACNU) plus VM26 and ACNU plus cytarabine (Ara-C) chemotherapy in addition to standard radiotherapy in patients with newly diagnosed malignant glioma. PATIENTS AND METHODS: From 1994 to 2000, 375 patients were randomly assigned to receive radiotherapy and cycles of ACNU 90 mg/m2 intravenously (IV) on day 1 and VM26 60 mg/m2 IV on days 1 to 3 (n = 183), or ACNU 90 mg/m2 IV on day 1 and Ara-C 120 mg/m2 IV on days 1 to 3 (n = 179), in 6-week intervals. Thirteen patients were not eligible after central neuropathology review. The remaining 362 patients had glioblastoma (n = 301) or anaplastic glioma (n = 61). RESULTS: Median survival and 2-year survival rates were 17.3 months and 25% for ACNU plus VM26, and 15.7 months and 29% for ACNU plus Ara-C in glioblastoma, and 60 months and 88% for ACNU plus VM26 and 62.5 months and 72% for ACNU plus Ara-C in anaplastic glioma. Multivariate analysis revealed no survival advantage for either arm or for subpopulations defined by histology, age, or KPS. Hematologic toxicity was more prominent in the ACNU plus Ara-C arm. CONCLUSION: The median survival times and 2-year survival rates for patients with anaplastic glioma and glioblastoma achieved in the NOA-01 trial compare favorably with historical trials and with the Radiation Therapy Oncology Group database. The toxicity profile favors ACNU plus VM26 for further evaluation.

Adolescent↗

Experimental thermoradiotherapy in malignant hepatocellular carcinoma.

PURPOSE: The human liver is known to be a relatively radiosensitive organ that develops clinically relevant late radiation hepatitis subsequent to whole liver treatment with total doses above 30 Gy in conventional fractionation. Experimental data, as well as clinical series, have demonstrated that hyperthermia of solid tumors in addition to radiotherapy enhances tumor growth inhibition and tumor control probability. We therefore developed an experimental model for combined radiotherapy and hyperthermia of the liver in transplantable rat Morris hepatoma 3924A. METHODS AND MATERIALS: A cube of approximately 8 mm(3) was implanted subcapsularly into the middle liver lobe of 59 male syngenic ACI rats weighing approximately 180-200 g. On Day 16 after tumor implantation, irradiation of the tumor-bearing liver with either 0 Gy/25 Gy/35 Gy/45 Gy total dose in 10 fractions +/- hyperthermia (target temperature 40-42 degrees C) twice a week was initiated. Energy deposition was monitored by temperature probes in the liver and esophagus of the rats. Determination of tumor volume with magnetic resonance imaging was performed 2 to 5 weeks after the end of therapy. The tumor growth rates could be estimated for 44 rats. If the growth rate was positive (37 rats), the inverse of the growth rate was interpreted as the time to 10-fold tumor volume. Otherwise the maximum observation time was considered as a censored value in a parametric survival analysis. RESULTS: Intrahepatic temperature probes showed a temperature plateau of greater than 40 degrees C after 5 to 8 min subsequent to initiation of hyperthermia. The target temperatures could be maintained for at least 22 min > or =40 degrees C and 10 min > or =41 degrees C, respectively. Median plateau temperature in liver, esophagus, and epicutaneously was 41.2 degrees C (standard deviation [SD] 0.7 degrees C; range 38.2 to 43.3 degrees C), 40.4 degrees C (SD 1.08 degrees C; range 38.9 to 41.8 degrees C), and 40.8 degrees C (SD 0.8 degrees C; range 38.2 to 42.7 degrees C), respectively. Elevation of the temperature in the esophagus correlated with intrahepatic temperatures in the range of 39-42 degrees C, r = 0.957. The increase in time to 10-fold tumor volume for each step of irradiation dosage was by 34% (95% confidence interval [CI] 20% to 49%) without hyperthermia and by 60% (95% CI 47% to 80%) with hyperthermia (p < 0.0001). CONCLUSION: Treatment outcome after experimental percutaneous thermoradiotherapy in intrahepatically implanted Morris hepatoma 3924A was related to total dose of irradiation and concurrently administered regional hyperthermia. An increased radiosensitivity due to hyperthermia (<42 degrees C) has to be assumed.

Animals↗

Radiotherapy for stages IIA/B testicular seminoma: final report of a prospective multicenter clinical trial.

PURPOSE: A prospective multicenter trial was initiated to evaluate the role of modern radiotherapy with reduced treatment portals for stage IIA and IIB testicular seminoma. PATIENTS AND METHODS: Patients with stages IIA/B disease (Royal Marsden classification) were assessable for the trial. Staging comprised computed tomography of the chest, abdomen, and pelvis as well as analysis of tumor markers alpha-fetoprotein and beta human chorionic gonadotropin. Linac-based radiotherapy was delivered to para-aortic and high ipsilateral iliac lymph nodes. The total doses were 30 Gy for stage IIA and 36 Gy for stage IIB disease. RESULTS: Between April 1991 and March 1994, 94 patients were enrolled for the trial by 30 participating centers throughout Germany. Seven patients were lost to follow-up. Median time to follow-up of 87 assessable patients was 70 months. There were 66 stage IIA and 21 stage IIB patients. One mediastinal and one field-edge relapse were observed in the stage IIA group. In the stage IIB group, there was one mediastinal and one mediastinal/pulmonary relapse. All patients were treated with a salvage regimen of platinum-based chemotherapy. Actuarial relapse-free survival at 6 years was 95.3% (95% confidence interval [CI], 88.9% to 100%) and 88.9% (95% CI, 74.4% to 100%) for stage IIA and IIB groups, respectively. Maximum acute side effects were 8% grade 3 nausea for stage IIA and 10% grade 3 nausea and diarrhea for stage IIB groups. No late toxicity was observed. CONCLUSION: Radiotherapy for stages IIA/B seminoma with reduced portals yields excellent tumor control at a low rate of acute toxicity and no late toxicity, which supports the role of radiotherapy as the first treatment choice for these patients.

Adult↗

Radiation therapy alone in early stage non-small cell lung cancer.

Among the patients with early stage (I/II) non-small cell lung cancer (NSCLC), there are those who, due to medical comorbidities, advanced age, or refusal, never undergo surgery. For them, exclusive radiation therapy (RT) has been the treatment of choice, achieving median survival times of 30 months and 5-year survival of up to 42%. Doses of > or =65 Gy with standard fractionation (or its radiobiological equivalent when altered fractionation is used) are necessary for long-lasting local control of the disease, with smaller tumors having a more favorable prognosis. The issue of elective nodal irradiation (ENI) remains controversial, since failure patterns identified local failure as the predominant pattern. None of the potential pretreatment patient- and tumor-related prognostic factors has been shown to clearly influence survival. Toxicity is generally mild to moderate, although high doses (e.g., 80 Gy) may carry a risk for an excessive rate of side effects. Conformal treatment and consideration of comorbidities such as altered lung function may be essential, since simultaneous supportive treatment of acute sequelae (mainly acute esophagitis) is necessary. RT is an effective treatment modality in technically operable, but medically inoperable patients with early stage NSCLC and offers a long-lasting cure.

Carcinoma, Non-Small-Cell Lung↗

Limited-disease small-cell lung cancer.

Substantial improvements in treatment outcome for limited-disease small-cell lung cancer (LD SCLC) have been achieved in the last two decades owing to the introduction of chemotherapy (CHT) consisting of cisplatin and etoposide (PE), and the understanding that thoracic radiation therapy (TRT) is an essential component in improving treatment outcome. In addition, a recent metaanalysis confirmed the importance of prophylactic cranial irradiation (PCI) in general treatment plans for patients who show a complete response to treatment. However, numerous questions remain unanswered regarding this disease. While TRT/PE/PCI is considered to be the standard treatment in the majority of centers worldwide, the emergence of new and effective drugs (e.g., topoisomerase I inhibitors and paclitaxel) for the treatment of LD SCLC will likely affect therapy strategies in the near future. Important issues regarding optimal doses and fractionation regimens, as well as the timing of TRT, remain to be resolved. While most centers currently use b.i.d. fractionation as a result of the Intergroup findings, high-dose standard TRT may also be beneficial. TRT volumes are also considered an important issue, since they likely relate to the incidence of both local failure and toxicity. Finally, the optimization of PCI (total dose, fractionation regimen, and timing) is already under way. The value of surgery is limited to peripheral tumors and poorly responding cancer, and to confirm histology or improve local control and survival.

Antineoplastic Combined Chemotherapy Protocols↗