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Radiation therapy for early stage Hodgkin's disease: Australasian patterns of care. Australasian Radiation Oncology Lymphoma Group.

PURPOSE: Analysis of treatment outcome for Stage I-IIA supradiaphragmatic Hodgkin's disease treated solely by irradiation in Australia and New Zealand. METHODS AND MATERIALS: Patients with supradiaphragmatic Hodgkin's disease only who were treated by irradiation alone with curative intent between 1969 to 1988 were retrospectively reviewed. Ten radiation oncology departments in Australia and New Zealand contributed patient data to the study. Patient, tumor, and treatment variables were recorded. Disease-free interval, survival, and complications were analyzed. RESULTS: Eight hundred and twenty patients were reviewed. The median age was 29 years. There were 437 men and 383 women. The distribution of 310 clinically staged patients was 170 stage IA, 5 IB, and 135 IIA. Five hundred and ten patients received laparotomies, and pathologic staging was as follows: IA 214, IB 13, IIA 283. The 10-year actuarial disease-free rate was 69% and overall survival rate was 79%. Increasing age, male sex, higher number of involved sites, the use of involved field irradiation, no staging laparotomy, and earlier year of treatment were significantly associated with an increased risk of relapse and lower survival. Actuarial 10-year survival following recurrence was 48%. Acute complications requiring interruption to treatment occurred in 46 patients (6%), but < 1% had their treatment permanently suspended. Actuarial complication rates at 10 years were: cardiac 2%, pulmonary 3% and thyroid 5%. There were 44 second malignancies including 10 non-Hodgkin's lymphomas, 3 leukemias, 7 lung, and 6 breast cancers. Mean delay to the development of a second cancer was 6 years. The 10-year actuarial rate of second malignancy was 5%. CONCLUSIONS: The Australasian experience of early stage Hodgkin's disease is consistent with the results in the published literature and confirms that irradiation produces a high cure rate with minimal toxicity.

Adult↗

Conformal radiation therapy with fixed shaped coplanar or noncoplanar radiation beam bouquets: a possible alternative to radiosurgery.

PURPOSE: Three-dimensional (3D) geometric conformation of the therapeutic dose volume to the shape of a target tissue volume is the motivation for both conformal radiotherapy and radiosurgery. Although noncoplanar arcs have a clear physical and geometric advantage over fixed fields for small spherical targets, those advantages are reduced for large or irregularly shaped targets where static fields can be individually shaped. We have developed a system that allows efficient and flexible design and reliable delivery of customized "bouquets" of fixed nonopposed coplanar or noncoplanar shaped fields, resulting in highly uniform dose distributions. This report describes our initial experience using beam bouquets to treat intracranial lesions. METHODS AND MATERIALS: Patients with primary (11) or metastatic (4) intracranial lesions with a maximum diameter less than approximately 6 cm, most of whom candidates for single-fraction radiosurgery, were treated with beam bouquets of four to eight nonopposed coplanar or noncoplanar beams. Doses ranged from 16-20 Gy in four fractions for recurrent lesions (8) to 45 to 68 Gy in 25 to 34 fractions for primary lesions (7). The patients were immobilized with custom foam head supports and face masks attached to a fixed base plate. Planning computed tomography scans were acquired, from which the physician developed the custom beam bouquet using 3D treatment-planning tools. The bouquet was designed based primarily on geometric concerns. The bouquet was subsequently modified to add wedge filters chosen by vector analysis of dose gradients to achieve uniform dose over the volume of beam crossfire. At the time of treatment, the isocenter was placed using the instructions provided by the treatment-planning system and pretreatment orthogonal port films were compared to digitally reconstructed radiographs (DRR) to assure proper isocenter placement. For several situations, the 3D dose distributions resulting from alternative coplanar and noncoplanar plans were compared. RESULTS: Each patient was treated without incident. Daily pretreatment port films showed excellent reproducibility of isocenter placement in 87% of setups. With short follow-up (0-12 months), two patients with recurrent glioblastoma experienced clinical deterioration 2 to 4 weeks following treatment. One had increased edema on scans and responded to steroids. Six patients clinically improved following radiation therapy. Review of alternative treatment plans reveals that the relative utility of coplanar vs. noncoplanar beams is likely dependent on the location of the lesion. Noncoplanar beam bouquets are likely preferable to coplanar beams when the target is located in the central regions of the head. Coplanar beams are likely adequate, and possibly preferable, for peripherally located targets. CONCLUSION: The biological advantages of fractionation and the physical advantages of radiosurgery are exploited with this approach. The use of multiple nonopposed coplanar or noncoplanar conformal wedged fields provides a uniform dose to the target and acceptable dose gradient at the target edge. This technique may prove to be an alternative to arc-based radiosurgery in some settings and has the potential advantages that fractionation should improve the therapeutic ratio, and each beam can be individually shaped to conform to irregularly shaped targets. Additional studies are underway to improve this system and better define its utility.

Adult↗

Reduction of radiotherapy-induced late complications in early breast cancer: the role of intensity-modulated radiation therapy and partial breast irradiation. Part II--Radiotherapy strategies to reduce radiation-induced late effects.

Radiotherapy after conservation surgery has been proven to decrease local relapse and death from breast cancer, and is now firmly established in the management of early breast carcinoma. Currently, the challenge is to optimise the therapeutic ratio by minimising treatment-related morbidity, while maintaining or improving local control and survival. The second part of this review examines the role of two approaches: intensity-modulated radiation therapy (IMRT) and partial breast irradiation, as means of improving the therapeutic ratio. Discussion of IMRT includes both inverse- and forward-planned methods: the breast usually requires minimal modulation to improve dose homogeneity, and therefore lends itself to simpler forward-planned IMRT techniques; whereas inverse-planned IMRT may be useful in selected cases. There are many dosimetry studies reporting the superiority of IMRT over conventional breast radiotherapy, but there is still a paucity of clinical data regarding patient benefit from these techniques. A critical literature review of clinical partial breast radiotherapy studies focuses on the influence of irradiated breast volume, dose and fractionation, and patient selection on normal tissue side-effects and local control. Clinical reports of partial breast irradiation show several encouraging, but some concerning results about local recurrence rates. Therefore, mature results from randomised trials comparing partial breast irradiation with whole-breast radiotherapy are required. Accurate localisation of the tumour bed and application of appropriate clinical target volumes and planning target volumes are discussed in detail, as these concepts are fundamental for partial breast irradiation.

Brachytherapy↗

Expression of the epidermal growth factor receptor and Her-2 are predictors of favorable outcome and reduced complete response rates, respectively, in patients with muscle-invading bladder cancers treated by concurrent radiation and cisplatin-based chemotherapy: a report from the Radiation Therapy Oncology Group.

PURPOSE: Erb-1 (epidermal growth factor receptor, EGFR) and Erb-2 (Her-2) are two of the best characterized members in the EGFR pathway. In many tumor types, overexpression of these proteins is associated with enhanced malignant potential. Our objective in this study was to investigate the clinical relevance of EGFR and Her-2 expression in bladder cancer cases from four prospective Radiation Therapy Oncology Group (RTOG) bladder preservation trials using cisplatin-containing chemoradiation (RTOG 8802, 8903, 9506, and 9706). METHODS AND MATERIALS: Tumors from 73 cases from patients with muscle-invading T2-T4a bladder cancers had slides interpretable for EGFR staining; 55 cases had slides interpretable for Her-2 staining. Additionally, the respective prognostic values of p53, pRB, and p16 immunostaining were concomitantly examined. Staining and interpretation of staining were done in a blinded manner, without knowledge of clinical outcome. Staining was judged as positive or negative. Subsequently, staining was correlated with clinical outcome. RESULTS: On univariate analysis, EGFR positivity was significantly associated with improved overall survival (p = 0.044); disease-specific survival (DSS) (p = 0.042); and DSS with intact bladder (p = 0.021). There was also a trend for association between EGFR expression and reduced frequency of distant metastasis (p = 0.06). On multivariate analysis adding tumor stage, tumor grade, whether a visibly complete transurethral resection of bladder tumor (TURBT) was done or not, and patient age to the model, EGFR positivity was significantly associated with improved DSS. On univariate analysis, Her-2 positivity was significantly associated with reduced complete response (CR) rates (50% vs. 81%, p = 0.026) after chemoradiation which remained significant on multivariate analysis. The other markers examined in this study were not found to have any prognostic value in this setting. CONCLUSION: Epidermal growth factor receptor expression appears to correlate significantly with improved outcome in bladder cancer, whereas Her-2 expression is significantly associated only with reduced CR rates after chemoradiation. Further investigations are warranted into how EGFR family members regulate response to chemoradiation in bladder cancer and their potential therapeutic implications.

Analysis of Variance↗

Phase I study of thoracic radiation dose escalation with concurrent chemotherapy for patients with limited small-cell lung cancer: Report of Radiation Therapy Oncology Group (RTOG) protocol 97-12.

PURPOSE: The purpose of RTOG 97-12 was to determine the maximum tolerated dose (MTD) of thoracic radiation therapy (RT) with concurrent chemotherapy for patients with limited-stage small-cell lung cancer. PATIENTS AND METHODS: Sixty-four patients received four cycles of cisplatin (60 mg/m(2) i.v.) and etoposide (120 mg/m(2) i.v. Days 1-3) (PE), with concurrent thoracic RT starting on Day 1. Thoracic RT was given during the first two cycles with 1.8 Gy/fraction daily to the clinical target volume, followed by thoracic RT to the gross tumor volume b.i.d. for the last 3, 5, 7, 9, or 11 treatment days (total dose 50.4, 54.0, 57.6, 61.2, or 64.8 Gy, respectively). The MTD was based on the dose that produced Grades 3-4 nonhematologic toxicity (mainly esophagitis and pneumonitis) in greater than 50% of patients. RESULTS: After the first 8 patients were enrolled in Arm 1, administration of etoposide was changed from 120 mg/m(2) i.v. on Days 2 and 3 of each cycle to 240 mg/m(2) p.o. for patient convenience as outpatients. Total thoracic RT doses from 50.4 Gy to 61.2 Gy over 5 weeks given with PE were well tolerated. Three of the first 5 patients in the 64.8 Gy arm developed Grade 3 acute esophagitis; the MTD was determined to be 61.2 Gy. Fifty-four (87%) of the 62 evaluable patients achieved a complete (68%) or partial (19%) tumor response. The 18-month survival was 25% for patients receiving 50.4 Gy and 82% for those receiving 61.2 Gy. CONCLUSIONS: The MTD for this accelerated thoracic RT regimen with concurrent PE was 61.2 Gy over 5 weeks.

Antineoplastic Combined Chemotherapy Protocols↗

Neoadjuvant hormone therapy and external-beam radiation for localized high-risk prostate cancer: the importance of PSA nadir before radiation.

PURPOSE: To examine the impact of various patient, disease, and treatment characteristics on outcome in patients treated with neoadjuvant hormone therapy (NAHT) and external-beam radiation therapy (EBRT) for clinically localized, high-risk prostate adenocarcinoma (initial prostate-specific antigen [PSA] level >20, Gleason score 8-10 or Stage > or = T3). METHODS AND MATERIALS: A retrospective chart review was conducted on 407 patients treated between 1991 and 2001 with NAHT and EBRT for high-risk prostate cancer. The effect of tumor (PSA level, Gleason score, and T stage) and treatment (NAHT duration, total-hormone duration, preradiation PSA) characteristics on rates of biochemical disease-free survival (bDFS), prostate cancer-specific survival, and overall survival were examined. RESULTS: Median follow-up time was 78 months (range: 5-140 months). Actuarial bDFS at 5 years was 52% (95% confidence interval [CI], 46% to 57%) for the entire group. On multivariate analysis, initial PSA level (p = 0.004), Gleason score (p = 0.005), and preradiation PSA level (p < 0.001) were predictive of bDFS, whereas age, T stage, duration of NAHT, and duration of total hormone therapy were not predictive of outcomes. Gleason score and preradiation PSA level were also predictive of prostate cancer-specific survival rates. CONCLUSION: Improved bDFS in patients with high-risk prostate cancer was associated with lower initial PSA level, lower Gleason score, and lower preradiation PSA level. The duration of NAHT did not have an impact on outcomes, but the preradiation PSA was an important predictor of bDFS in high-risk patients.

Aged↗

Dose as a function of liver volume and planning target volume in helical tomotherapy, intensity-modulated radiation therapy-based stereotactic body radiation therapy for hepatic metastasis.

PURPOSE: Stereotactic body radiation therapy (SBRT) has been shown to be an effective, well-tolerated treatment for local control of tumors metastatic to the liver. Multi-institutional Phase II trials are examining 60 Gy in 3 fractions delivered by linac-based, 3D-conformal IMRT. HiArt Helical TomoTherapy is a treatment unit that delivers co-planar helical IMRT that is capable of image-guided SBRT. We hypothesized that the maximum tolerable dose (MTD) delivered to a lesion by Helical TomoTherapy-based SBRT could be predicted based on the planning target volume (PTV) and liver volume. METHODS AND MATERIALS: To test this, we performed inverse treatment planning and analyzed the dosimetry for multiple hypothetical liver gross tumor volumes (GTV) with conventional PTV expansions. Inverse planning was carried out to find the maximum tolerated SBRT dose up to 60 Gy to be delivered in 3 fractions based on the dose constraint that 700 cc of normal liver would receive less than 15 Gy. RESULTS: Regression analysis indicated a linear relationship between the MTD, the PTV and the liver volume, supporting our hypothesis. A predictive equation was generated, which was found to have an accuracy of +/-3 Gy. In addition, dose constraints based on proximity to other normal tissues were tested. Inverse planning for PTVs located at varying distances from the heart, small bowel, and spinal cord revealed a predictable decrease in the MTD as the PTV increased in size or approached normal organs. CONCLUSIONS: These data provide a framework for predicting the likely MTD for patients considered for Helical TomoTherapy liver SBRT.

Humans↗

Long-Term Outcomes of Radiation Monotherapy Versus Combined Radiation Monotherapy + Hormone Therapy in Low-Risk Early-Stage Breast Cancer Patients 70 Years or Older After Breast-Conserving Surgery.

PURPOSE: Standard therapy for breast cancer after breast-conserving surgery is radiation therapy (RT) plus hormone therapy (HT). For patients with a low-risk of recurrence, there is an interest in deescalating therapy. METHODS AND MATERIALS: A retrospective study was carried out for patients treated at the Swedish Cancer Institute from 2000 to 2015, aged 70 years or older, with pT1N0 or pT1NX estrogen receptor-positive and ERBB2-negative unifocal breast cancer without positive surgical margins, high nuclear grade, or lymphovascular invasion. RESULTS: Patient numbers were sufficient to carry out analyses for RT + HT (n = 307) and RT alone (n = 148). The median follow-up was 9.6 years. There were no statistically significant differences in adjusted overall survival (OS), disease-specific death, progression-free survival (PFS), distant recurrence, and second primary cancers with RT monotherapy compared with RT + HT. Cumulative rates of all of these outcomes were <5%, even at 15 years of follow-up, regardless of treatment, greatly outweighed by the incidence of death from other causes in this elderly population. In matched analysis, we calculated a hazard ratio of 1.12 (95% CI, 0.82-1.53) for RT versus RT + HT for OS and a hazard ratio of 1.12 (95% CI, 0.82-1.53) for RT versus RT + HT for PFS. CONCLUSIONS: Our data suggest that elderly, low-risk breast cancer patients have similarly high OS and PFS with low rates of local recurrence, distant recurrence, and death from breast cancer with much higher rates of death from competing causes, whether treated with RT or HT + RT. These patients are likely to die of other causes without disease recurrence, regardless of which of these treatments is used. Thus, they may benefit from the administration of more modern forms of breast irradiation without the need for adjuvant systemic hormone therapy. A detailed analysis of which clinical, pathologic, genomic, and comorbidity variables are needed to select these patients.

Humans↗

Radiation-induced bullous pemphigoid: a systematic review of an unusual radiation side effect.

BACKGROUND: Percutaneous radiotherapy (RT) may cause a range of acute and late side effects of the skin within the irradiated area. In rare cases radiotherapy can cause bullous pemphigoid (BP). BP is reported to occur mainly within irradiated fields following radiation treatment. Exceptionally, BP may arise during RT. It is unclear which mechanism exactly triggers BP following megavoltage irradiation and whether there is a potential association with hormonal anticancer treatment. METHODS: A systematic literature based review was performed. Publications reporting histologically confirmed BP and a treatment with RT were retrieved based on a standardized query using electronic databases. A standardized quality assessment was applied. RESULTS: Out of 306 potentially relevant publications 21 were identified to be relevant and included in this review. An association between RT and BP was reported in 27 patients. The majority developed BP after RT and a median dose of 50 Gy. Four patients developed BP during RT after a minimal dose of 20 Gy. CONCLUSIONS: BP induced by RT was observed predominantly in patients with breast cancer. In all reported cases, there is a clear relationship with RT. Therefore, BP may be considered as RT-induced side effect. RT can induce a BP following a minimal dose of 20 Gy. New biological agents may play a role in the future treatment of BP.

Breast Neoplasms↗

The effects of two UVB radiation-absorbing sunscreens on UV radiation-induced carcinogenesis, suppression of the contact hypersensitivity response and histological changes in the hairless mouse.

The research summarised in this report suggests that the two UVB-absorbers, o-PABA and 2-EHMC, have different modes of protection against UV radiation-induced immunosuppression, carcinogenesis and histological alterations, that appear to be independent of their SPF values, within experimental limits. The UVB-absorber o-PABA appears offer a valuable level of protection against photocarcinogenesis.

4-Aminobenzoic Acid↗

Supraglottic laryngectomy with postoperative radiation versus primary radiation in the management of supraglottic laryngeal cancer.

PURPOSE: The purpose of this review was to study the results of horizontal partial laryngectomy (HPL) for supraglottic laryngeal cancer (stages N0 and N+) and the effects and morbidity of postoperative radiation therapy (RT), especially after bilateral neck dissection, as opposed to primary RT. PATIENTS AND METHODS: Of a total of 89 patients, 26 were treated by HPL, 44 by primary RT, and 19 by total laryngectomy (TL). Of the HPL patients, 19 of 26 had neck dissection, 10 were bilateral. Twelve of the patients received postoperative RT, and 10 of 12 procedures were combined with neck dissection. RESULTS: When comparing the results of HPL and primary RT, the locoregional control was equivalent for the N0 patients, but HPL showed better results in locoregional control for the N+ patients (P < .0024). Postoperative RT with or without bilateral neck dissection did not show an increase in postoperative morbidity. CONCLUSION: Therefore, our data suggest that there should be no hesitation in giving postoperative RT where indicated, after performing HPL plus unilateral or bilateral neck dissection. Patients that are stage N0 should receive primary RT.

Humans↗

Phase II study of topotecan plus cranial radiation for glioblastoma multiforme: results of Radiation Therapy Oncology Group 9513.

PURPOSE: A Phase II trial was conducted by the Radiation Therapy Oncology Group (RTOG) to compare the survival of patients with glioblastoma multiforme treated with topotecan combined with standard cranial radiotherapy (RT) for matched patients treated in prior RTOG studies. A secondary objective was to document the acute and late toxicities of this combination of chemotherapy and RT. METHODS AND MATERIALS: Eighty-seven patients with histologically confirmed glioblastoma multiforme received standard cranial RT (60 Gy/30 fractions in 6 weeks) plus topotecan 1.5 mg/m2 per day i.v. for 5 d/wk every 3 weeks for 3 cycles. Eighty-four patients were evaluated, of whom 60 (71%) were > or =50 years, 44 (52%) were men, and 61 (73%) had a Karnofsky performance status of > or =80. Twenty-nine percent of patients had undergone biopsies, 48% partial resections, and 21% gross total resections. Two resections were unspecified as to the extent of tumor removal. Fourteen percent of patients were recursive partitioning analysis Class III, 46% were Class IV, 35% were Class V, and 5% were Class VI. RESULTS: The median survival was 9.3 months. Sixty-seven patients (80%) had progression. The 1-year survival rate was 32%. One patient remained alive without recurrence. RTOG 9513 patients were matched with patients in an RTOG clinical trial database from previous clinical trials. The matching variables were age, Karnofsky performance status, mental status, and prior surgery. No statistically significant difference was found between the survival of the study patients and that of the matched patients from the RTOG database. Fifty-four percent of patients had Grade IV acute toxicity. The toxicity was primarily hematologic. Four patients had Grade III late central nervous system toxicities. CONCLUSION: Topotecan administered at a dose of 1.5 mg/m2 per day i.v. for 5 d/wk every 3 weeks for 3 cycles given concurrently with standard cranial RT for glioblastoma does not produce a statistically significant survival advantage over previously tested therapies. Other methods of administration of topotecan or other camptothecins may provide more effective radiosensitization.

Aged↗

Addition of chemotherapy to radiation therapy alters failure patterns by cell type within non-small cell carcinoma of lung (NSCCL): analysis of radiation therapy oncology group (RTOG) trials.

PURPOSE: To evaluate the influence of cell type within non-small cell carcinoma of lung (NSCCL) on failure patterns when chemotherapy (CT) is combined with radiation therapy (RT). METHODS AND MATERIALS: Data from 4 RTOG studies including 1415 patients treated with RT alone, and 5 RTOG studies including 350 patients also treated with chemotherapy (RT + CT) were analyzed. Patterns of progression were evaluated for squamous cell carcinoma (SQ) (n = 946), adenocarcinoma (AD) (n = 532) and large cell carcinoma (LC) (n = 287). RESULTS: When treated with RT alone, SQ was more likely to progress at the primary site than LC (26% vs. 20%, p = 0.05). AD and LC were more likely to progress in the brain than SQ (20% and 18% vs. 11%, p = 0.0001 and 0.011, respectively). No differences were found in intrathoracic and distant metastasis by cell type. When treated with RT + CT, AD was less likely to progress at the primary than either SQ or LC (23% vs. 34% and 40%, respectively; p = 0.057 and 0.035). AD was more likely than SQ to metastasize to the brain (16% vs. 8%, p = 0.03), and other distant sites (26% vs. 14%,p = 0.019). No differences were found in intrathoracic metastasis. LC progressed at the primary site more often with RT + CT than with RT alone (40% vs. 20%, p = 0.036). Death with no clinical progression was more likely with SQ than AD or LC for RT alone and RT + CT (p < 0.01). Brain metastasis was altered little by the addition of CT, but other distant metastases were significantly decreased (p < 0.001) in all cell types by the addition of CT. CONCLUSION: CT, although effective in reducing distant metastasis in all types of NSCCL, has different effects on the primary tumor by cell type, and has no effect on brain metastasis or death with no progression. Different treatment strategies should be considered for the different cell types to advance progress with RT + CT in NSCCL.

Adenocarcinoma↗

Differential behaviour of two cyanobacterium species to UV radiation. Artificial UV radiation induces phycoerythrin synthesis.

Altitude is an important factor contributing to the local UV-B climate. In the European Alps solar UV-B increases approximately 21% 1000 m-1. A Nostoc muscorum (UTEX 389) originating from Scotland and a Nostoc sp. isolated from a highland lake (Yanaqocha) located 3980 m above sea level (Cusco, Perú) have been used in a study where the tolerance to UV radiation (UVR) stress of both species was determined. Following irradiation doses of 15 kJ UV (UV-A plus UV-B, equivalent to approximately 6 h exposure to unfiltered solar light at noon for a standard midlatitude region with normal ozone concentration), the viability of Nostoc sp. is 30% compared to 3% for Nostoc muscorum. UV-B induces the reduction of the number of phycobilisomes per cell, phycobilisome disassembly and/or degradation as well as phycobilisome uncoupling. Following UV exposure, phycoerythrin (PE) fluorescence emission increases dramatically in both species, indicating accumulation of PE in the phycobilisome rods. The detected increase in PE due to UVR is confirmed using a monoclonal antibody anti-PE.

Cyanobacteria↗

Formation of radiation-induced cross-links between thymine and tyrosine: possible model for cross-linking of DNA and proteins by ionizing radiation.

A model for radiation-induced cross-linking of DNA and proteins has been developed. It is based on initial formation of free radicals on a DNA base, i.e., thymine, and on an amino acid, i.e., tyrosine. It was demonstrated that interaction of these radicals is highly favored as measured by their kinetics and the cross-linked products. The gas chromatography-mass spectrometry methodology used for the identification of the thymine-tyrosine cross-links is suggested as an experimental approach in the measurements of biological cross-links.

Chromatography, Gas↗

[Possibilities of radiation-dose reduction in the treatment of Hodgkin's disease. I. Exclusion of the mediastinum from the radiation field in primary high-cervical or infradiaphragmatic involvement and stage I or II (author's transl)].

A retrospective analysis on 482 patients with localised Hodgkin's disease revealed that none of those with primary high-cervical or primary infradiaphragmatic involvement had any infiltration of the mediastinum, either at the time or later. As a result, prophylactic mediastinal radiation was not practised if high-cervical or infradiaphragmatic lymph-nodes had been affected first. None of these patients had any mediastinal recurrence after at least seven years.

Adolescent↗

Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma.

BACKGROUND: Bulky stage IB cervical cancers have a poorer prognosis than smaller stage I cervical cancers. For the Gynecologic Oncology Group, we conducted a trial to determine whether weekly infusions of cisplatin during radiotherapy improve progression-free and overall survival among patients with bulky stage IB cervical cancer. METHODS: Women with bulky stage IB cervical cancers (tumor, > or =4 cm in diameter) were randomly assigned to receive radiotherapy alone or in combination with cisplatin (40 mg per square meter of body-surface area once a week for up to six doses; maximal weekly dose, 70 mg), followed in all patients by adjuvant hysterectomy. Women with evidence of lymphadenopathy on computed tomographic scanning or lymphangiography were ineligible unless histologic analysis showed that there was no lymph-node involvement. The cumulative dose of external pelvic and intracavitary radiation was 75 Gy to point A (cervical parametrium) and 55 Gy to point B (pelvic wall). Cisplatin was given during external radiotherapy, and adjuvant hysterectomy was performed three to six weeks later. RESULTS: The relative risks of progression of disease and death among the 183 women assigned to receive radiotherapy and chemotherapy with cisplatin, as compared with the 186 women assigned to receive radiotherapy alone, were 0.51 (95 percent confidence interval, 0.34 to 0.75) and 0.54 (95 percent confidence interval, 0.34 to 0.86), respectively. The rates of both progression-free survival (P<0.001) and overall survival (P=0.008) were significantly higher in the combined-therapy group at four years. In the combined-therapy group there were higher frequencies of transient grade 3 (moderate) and grade 4 (severe) adverse hematologic effects (21 percent, vs. 2 percent in the radiotherapy group) and adverse gastrointestinal effects (14 percent vs. 5 percent). CONCLUSIONS: Adding weekly infusions of cisplatin to pelvic radiotherapy followed by hysterectomy significantly reduced the risk of disease recurrence and death in women with bulky stage IB cervical cancers.

Adult↗