Treatment of rectal cancer.
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Antineoplastic Combined Chemotherapy Protocols↗
Biomedical subjects
Wolfgang Hinkelbein
Publications and source records attributed to Wolfgang Hinkelbein.
Proton or photon irradiation for hemangiomas of the choroid? A retrospective comparison.
PURPOSE: The aim of this study was to compare, on a retrospective basis, the results of therapy in patients with uveal hemangioma treated with photon or proton irradiation at a single center. METHODS: From 1993 to 2002 a total of 44 patients were treated. Until 1998 radiotherapy was given with 6 MV photons in standard fractionation of 2.0 Gy 5 times per week. In 1998 proton therapy became available and was used since then. A dose of 20 to 22.5 Cobalt Gray Equivalent (CGE) 68 MeV protons was given on 4 consecutive days. Progressive symptoms or deterioration of vision were the indications for therapy. RESULTS: Of the 44 patients treated, 36 had circumscribed choroidal hemangiomas and 8 had diffuse choroidal hemangiomas (DCH) and Sturge-Weber syndrome. Of the patients, 19 were treated with photons with a total dose in the range of 16 to 30 Gy. A total of 25 patients were irradiated with protons. All patients with DCH but 1 were treated with photons. Stabilization of visual acuity was achieved in 93.2% of all patients. Tumor thickness decreased in 95.4% and retinal detachment resolved in 92.9%. Late effects, although generally mild or moderate, were frequently detected. In all, 40.9% showed radiation-induced optic neuropathy, maximum Grade I. Retinopathy was found in 29.5% of cases, but only 1 patient experienced more than Grade II severity. Retinopathy and radiation-induced optic neuropathy were reversible in some of the patients and in some resolved completely. No differences could be detected between patients with circumscribed choroidal hemangiomas treated with protons and photons. Treatment was less effective in DCH patients (75%). CONCLUSIONS: Radiotherapy is effective in treating choroidal hemangiomas with respect to visual acuity and tumor thickness but a benefit of proton therapy could not be detected. Side effects are moderate but careful monitoring for side effects should be part of the follow-up procedures.
Adolescent↗
Uterus necrosis after radiochemotherapy in two patients with advanced cervical cancer.
BACKGROUND: Simultaneous platinum-based radiochemotherapy is the standard of care for patients with advanced or node-positive cancer of the uterine cervix. A large body of literature concerning therapy-related acute and late morbidity is available. Chemoradiation-associated necrosis of the uterus has not been described so far. CASE REPORT: Two patients are reported who were treated by combined chemoradiation between 2004 and 2005 for histologically confirmed cervical cancer following laparoscopic staging. Both patients were diagnosed with squamous cell cancer of the cervix FIGO stage IIB (T2b pN1 pM1 LYM G2) and FIGO IIIA (T3a pN1 M0 G2), respectively. External-beam radiotherapy was applied in a 3-D-planned four-field technique, covering pelvic lymph nodes and primary tumor. Patient #1 received additional paraaortic irradiation. Patient #2 underwent 5 x 5 Gy brachytherapy covering the tumor. Simultaneously, cisplatin was given to both patients. Following chemoradiation, both patients developed pelvic pain and an elevation of C-reactive protein (CRP) in the presence of a normal leukocyte count. Both patients underwent relaparoscopy, and necrosis of the uterus combined with partial necrosis of the bladder was diagnosed in patient #1. Patient #1 underwent total supralevatoric exenteration and patient #2 laparoscopically assisted hysterectomy with bilateral salpingo-oophorectomy. CONCLUSION: In patients with persisting or incident pelvic pain, questionable findings in imaging techniques and/or elevated inflammation parameters following completion of chemoradiation for cervical cancer, differential diagnosis should include radiogenic necrosis of the uterus and other pelvic organs. Laparoscopy is an ideal technique to exclude or confirm this diagnosis.
Adult↗
Interindividual variability of lymph drainages in patients with cervical cancer. Implication on irradiation planning.
BACKGROUND AND PURPOSE: Lymph node metastases and the number of positive lymph nodes are important prognostic factors for patients with cervical cancer. The most important route is the lateral drainage via the obturator to the internal and external iliac and common iliac area. The risk for common iliac lymph node metastases is increased in patients with positive pelvic or paraaortic lymph nodes. Positive common iliac lymph nodes are associated with a poorer prognosis than positive pelvic lymph nodes excluding common iliac group. For radiation planning in patients with cervical cancer, lymph node regions at high risk for metastases have to be encompassed. Usually, standard fields are used with the upper field border on the fourth/fifth lumbar vertebra. The authors evaluated whether standard fields are sufficient for encompassing the common iliac lymph nodes. PATIENTS AND METHODS: Pretreatment computed tomographic (CT) images of 42 patients with cervical cancer were evaluated to locate the aortic bifurcation and the subsequent common iliac lymph drainage. Anatomy of the lymph drain was correlated with standard radiation portals. RESULTS: In 17/42 patients (40%) the aortic bifurcation lay superior to the upper field border. In an additional nine patients (21%) the bifurcation was located on the level of the upper field border. In 26/42 patients (62%) standard radiation fields encompassed the common iliac lymph nodes insufficiently. CONCLUSION: Common iliac lymph node metastases are found in up to 50% of patients with node-positive cervical cancer. The results of this study demonstrate an unsatisfactory coverage of the common iliac lymph drain by standard fields in most patients. Thus it is necessary to individualize the planning target volume and to include the whole common iliac vessels according to the patient's anatomy on radiation treatment planning CT in order to improve local control.
Female↗
Proton therapy of uveal melanomas: intercomparison of MRI-based and conventional treatment planning.
BACKGROUND AND PURPOSE: Proton therapy for uveal melanoma provides high-conformal dose application to the target volume and, thus, an optimal saving of the organs at risk nearby. Treatment planning is done with the model-based treatment-planning system EYEPLAN. Tumor reconstruction is based only on a fundus composite, which often leads to an overestimation of the clinical target volume (CTV). The purpose was to exploit MRI on trial in a proton therapy-planning system by using the novel image-based treatment-planning system OCTOPUS. PATIENTS AND METHODS: Ten patients with uveal melanomas received both a high-resolution planning CT and MRI of the eye. MR examinations were made with an eye coil. EYEPLAN requires eye geometry data for modeling, and tantalum marker clips for submillimeter positioning and additional information from ultrasound and 3-D imaging. By contrast, OCTOPUS provides the full integration of 3-D imaging (e. g., CT, MRI). CTVs were delineated in each slice. For all patients, CTVs (EYEPLAN vs. OCTOPUS) were compared intraindividually. RESULTS: OCTOPUS planning led to a mean reduction of the target volume by a factor of 1.7 (T1-weighted [T1w]) and 2.2 (T2w) without compromising safety. The corresponding field size could be scaled down on average by a factor of 1.2 (T1w) and 1.4 (T2w), respectively. CONCLUSION: Compared with the conventional EYEPLAN, MRI-based treatment planning of ocular tumors with OCTOPUS could be a powerful tool for reducing the CTV and, consequently, the treatment volume and the field size. This might be translated into a better patient compliance during treatment and a decreased late toxicity.
Adolescent↗
Radiation-related damage to dentition.
Because of typical tissue reactions to ionising radiation, radiotherapy in the head and neck region usually results in complex oral complications affecting the salivary glands, oral mucosa, bone, masticatory musculature, and dentition. When the oral cavity and salivary glands are exposed to high doses of radiation, clinical consequences including hyposalivation, mucositis, taste loss, trismus, and osteoradionecrosis should be regarded as the most common side-effects. Mucositis and taste loss are reversible consequences, usually subsiding early post-irradiation, whereas hyposalivation is commonly irreversible. Additionally, the risk of rampant tooth decay with its sudden onset and osteonecrosis is a lifelong threat. Thus, early, active participation of the dental profession in the development of preventive and therapeutic strategies, and in the education and rehabilitation of patients is paramount in consideration of quality-of-life issues during and after radiotherapy. This Review focuses on the multifactorial causes of so-called radiation caries and presents possible treatment strategies to avoid loss of dentition.
Dental Caries↗
Is there a benefit of pretreatment laparoscopic transperitoneal surgical staging in patients with advanced cervical cancer?
OBJECTIVE: At present, cervical cancer remains the only gynecologic tumor, which is staged by clinical examination according to FIGO. This is associated with a high percentage of over- and understaging of tumor extent. With the operative, especially laparoscopic staging, exact information about intraabdominal tumor spread, lymph node metastases, and involvement of adjacent organs is possible. However, the advantage of operative staging is still discussed controversially. The aim of this study is to describe the laparoscopic transperitoneal staging procedure in patients with cervical cancer and their oncologic outcome after primary chemoradiation. METHODS: From November 1994 to October 2003, 456 consecutive patients with histologically confirmed primary cervical cancer were admitted to the Department of Gynecology of the Friedrich-Schiller-University Jena, Germany. Out of these, 84 patients with locally advanced tumor (tumor size>or=4 cm) and/or lymph node involvement and/or tumor infiltration to bladder or rectum were selected by a standardized laparoscopic staging procedure for primary chemoradiation. Data of surgery, chemoradiation, and follow-up were analyzed retrospectively for these patients. RESULTS: The mean age of the patients was 54 years (26-80), and the mean body-mass-index was 24.8 (17.9-42.2). Preoperative clinical evaluation showed a stage distribution according to FIGO with stage IB1 in 15.5%, IB2 in 15.5%, IIA in 8.3%, IIB in 23.8%, IIIA in 8.3%, IIIB in 21.4%, IVA in 6%, and IVB in 1.2%. In 15 out of 84 (17.8%) patients, intraabdominal tumor spread was diagnosed by laparascopy. In 24 out of 84 (28.5%) patients, invasion of bladder and/or rectum was proven histologically after biopsy. In 60 out of 84 (71%) patients, lymph node metastases were confirmed histologically. In 2 out of 13 patients with FIGO-stage Ib1, skip metastases in infrarenal paraaortic lymph nodes were seen. Removal of more than 5 pelvic and/or more than 5 positive paraaortic lymph nodes was associated with significant improvement of overall survival. According to the histological findings following laparoscopic staging in 36 out of 84 (43%) patients, a higher tumor stage was diagnosed. If tumor involvement of lymph nodes is also included, an upstaging in 73/84 (87%) of patients has to be noted down. Downstaging was not necessary in any patient following laparoscopic evaluation. CONCLUSION: Only operative staging gives exact information about tumor extension in patients with locally advanced and/or nodal positive cervical cancer and allows individual treatment planning. This can be done successfully by a transperitoneal laparoscopic approach without serious adverse effects delaying chemoradiation. Debulking of tumor-involved lymph nodes significantly improves overall survival and should be performed prior to primary chemoradiation. Laparoscopic staging should be the basis for all treatment studies in order to group patients according to true tumor extent.
Adult↗
Treatment of localized lymphoma.
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Antineoplastic Combined Chemotherapy Protocols↗
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↗
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↗
Is a diagnostic CT of the brain indicated in patients with choroidal metastases before radiotherapy?
BACKGROUND AND PURPOSE: There is no evidence in the literature about the incidence of synchronous brain metastases in patients with choroidal metastases. This is of major importance, because the radiation fields of choroidal metastases and, later on, brain metastases, if treated consecutively, are partly overlapping, thus potentially increasing the rate of late side effects such as brain necrosis. The goal of this study was to determine the frequency of synchronous brain metastases. PATIENTS AND METHODS: 50 patients with choroidal metastases were enrolled into a study of the "Arbeitsgemeinschaft Radiologische Onkologie" of the German Cancer Society (ARO 95-08) with standardized 40 Gy radiotherapy, 2 Gy single dose. All patients were staged before treatment with a computed tomography of the brain (CCT). No patient showed clinical signs of brain metastases. RESULTS: 13 out of 50 patients (26%) had brain metastases in the CCT leading to radiotherapy of the brain and choroidal metastases in one volume. CONCLUSION: A CCT is indicated at the diagnosis of choroidal metastases for screening of synchronous brain metastases. The incidence is about 25%, and the diagnosis of brain metastases results in a different target volume: the whole brain including the posterior parts of the eyes compared to the posterior parts of the eyes alone. Therefore, the risk of late side effects could be reduced compared with an additional later radiotherapy of the whole brain with partly overlapping fields.
Adult↗
Proton or stereotactic photon irradiation for posterior uveal melanoma? A planning intercomparison.
BACKGROUND AND PURPOSE: Proton and stereotactic radiotherapy with photons (SRT) are both used to treat choroidal melanomas in proximity to optic disk and fovea centralis, a situation where plaque therapy is prone to complications. A comparative treatment- planning study was done to assess the capability of both modalities to preserve vision. PATIENTS AND METHODS: In ten patients treated with 68-MeV protons, SRT with 6-MV photons was planned. Structures most important for visual acuity (fovea and optic disk, optic nerve) were contoured identically for both therapies. Safety margins of 1.5 mm for proton therapy were reduced to 1.0 mm for SRT. RESULTS: Proton-beam therapy was superior in eight of ten situations, and this result did not differ significantly by changes in the weighting of the different parameters analyzed. CONCLUSION: When dose deposition to those structures most important for the preservation of vision is taken into account, under the conditions examined proton therapy offers an advantage in the majority of the patients evaluated.
Eye Injuries↗
Recurrent rectal cancer within the pelvis. A multicenter analysis of 123 patients and recommendations for adjuvant radiotherapy.
BACKGROUND AND PURPOSE: Recommendations for radiation ports in adjuvant radiation therapy for rectal cancer are mainly based on analysis of recurrence patterns. To evaluate whether changes in surgical technique have influenced this pattern of recurrence, a multicenter retrospective analysis was carried out on a patient population treated recently. PATIENTS AND METHODS: 123 patients were evaluated with the help of a CT-based self-developed 3-D data file system and an extensive questionnaire. Major inclusion criteria (one sufficient) for eligibility were: histological confirmation, clear bone destruction, and a positive PET scan, or at least three minor criteria: progressive soft tissue mass, invasion of adjacent organs on follow-up CT or MRI, rising tumor markers, and typical appearance in cross-sectional imaging. Clinical or serologic signs of inflammation were exclusion criteria. RESULTS: Initially, 54% of the evaluated patients were N0; in the remainder, N1 and N2 were distributed evenly. Initial T-category was T1 in 2%, T2 in 24%, T3 in 60%, and T4 in 13%, the male-to-female ratio was 2:1. Recurrent tumors were mainly situated in the posterior part of the bony pelvis as displayed in the figures. When abdominoperineal resection was compared to low anterior resection as primary operation, there was a significant difference in extension of recurrent tumors in the inferior parts of the pelvis (p<0.025 in all statistical tests applied), whereas no significant difference was found in the superior parts of the pelvis. CONCLUSION: Based on these results, a modest field size reduction in adjuvant radiotherapy for rectal cancer seems feasible, offering the perspective of a reduction in acute and late side effects.
Adult↗
Proton therapy of uveal melanomas in Berlin. 5 years of experience at the Hahn-Meitner Institute.
BACKGROUND AND PURPOSE: In June 1998, proton-beam therapy of ocular tumors started at the Hahn-Meitner Institute Berlin, Germany. The purpose of the present study is to evaluate treatment outcome for uveal melanomas. PATIENTS AND METHODS: 245 consecutive patients with primary melanoma of the uvea were treated from June 1998 to April 2003 with a 68-MeV proton beam. In 96.2% of all patients, a uniform fractionation scheme was applied: single dose 15 CGE (cobalt gray equivalent), total dose 60 CGE on 4 consecutive days. Follow-up is available in 229 patients. RESULTS: At the time of median follow-up (18.4 months), local control is 96.4% and 95.5% at 3 years. Eye retention rate is 92.6% at 20 months (median follow-up) and 87.5% at 3 years. CONCLUSION: Proton-beam irradiation of uveal melanomas at the Hahn-Meitner Institute after the first 5 years of its initiation reveals local tumor control and eye retention rates in the range of other centers with larger experience. Delivering high treatment quality in hadron therapy from the beginning has been achieved.
Adolescent↗
[Five years of proton therapy of eye neoplasms at the Hahn-Meitner Institute, Berlin].
Eye tumors (choroidal melanomas, iris melanomas, and choroidal hemangiomas) are being treated with 68 MeV protons since 1998 at the Ion Beam Laboratory of the Hahn-Meitner Institute of Berlin (Germany's first proton therapy center), in cooperation with the Charité University Hospital in Berlin, Campus Benjamin Franklin. The proton beam, generated via a combination of Van de Graaff accelerator and cyclotron, is prepared by passive shaping for conformal tumor irradiation. A digital X-ray verification of the tumor location with the patient in sitting position limits the position uncertainties to a maximum of 0.3 mm. The treatment planning is performed using the program EYEPLAN. OCTOPUS, a CT-based planning program developed in cooperation with the German Cancer Research Center of Heidelberg, is under pre-clinical testing. Thus far, more than 400 patients have been irradiated. The first results are comparable to those obtained in other proton therapy centers. At the end of 2002, the University Hospital of Essen has also become a cooperation partner of the Hahn-Meitner Institute.
Academies and Institutes↗
Radiochemotherapy in unresectable pancreatic cancer.
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Chemotherapy, Adjuvant↗
Pelvic sidewall involvement in recurrent rectal cancer.
BACKGROUND AND AIMS: The lateral pelvic sidewall is an area not routinely dissected during standard operative procedures in surgery for rectal cancer in Western countries. This study analyzed data to evaluate the pattern of recurrence in rectal cancer with special emphasis on lateral tumor extension in a recently treated patient population. PATIENTS AND METHODS: In a multicenter retrospective study 123 patients were evaluated by our own CT-based three-dimensional datafile system and an extensive questionnaire. Patients had histological confirmation, clear bone destruction, a positive PET scan, and at least three minor criteria: progressive soft tissue mass, invasion of adjacent organs on follow-up CT or MRI, rising tumor markers, and typical appearance in cross-sectional imaging. Clinical or serological signs of inflammation were exclusion criteria. Initially 54% of the evaluated patients were N0, and the others were distributed evenly between N1 and N2; initial T stage was T1 in 2%, T2 in 24%, T3 in 60%, and T4 in 13%. RESULTS: . Recurrent tumors were situated mainly in the posterior part of the bony pelvis. The pelvic side wall was a rare site of recurrence and involved in fewer than 5%. When abdominoperineal resection was compared to low anterior resection as primary operation, there was a significant difference in extension of recurrent tumors in the inferior parts of the pelvis; no significant differences were found in superior or lateral parts of the pelvis. CONCLUSION: Because most tumor recurrences arise in the central pelvis, extending surgery to include dissecting the iliac vessels would probably offer only a moderate benefit, which must be balanced against potential side effects.
Adult↗
Salvage radiotherapy in patients with persisting prostate-specific antigen after radical prostatectomy for prostate cancer.
Salvage radiotherapy in patients with persisting prostate-specific antigen (PSA) after radical prostatectomy for prostate cancer offers an approach to reduce local recurrence rates and to improve the rate of biochemical freedom from relapse. 30-70% of these patients experience a decrease in their PSA to an undetectable range; in about 40-50% of these patients, PSA remains stable after 5 years. Therefore, radiation therapy offers these patients an ultimate chance of cure. The pre-irradiation PSA value is of particular importance. The PSA level should not exceed 2 ng/ml because otherwise the rate of distant metastases increases significantly. Serious side effects are apparently low, thus confirming the suitability of this therapeutic approach.
Humans↗