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[CHARTWEL-Bronchus (ARO 97-1): a randomized multicenter trial to compare conventional fractionated radiotherapy with CHARTWEL radiotherapy in inoperable non-small-call bronchial carcinoma].

BACKGROUND: The CHART-bronchus trial sponsored by the Medical Research Council showed an improvement in survival of 10% compared to conventional fractionation to 60 Gy when patients with inoperable non-small-cell lung cancer (NSCLC) were treated with CHART to 54 Gy. At present it is not known whether this survival advantage holds when the dose of conventional treatment is increased and whether CHART can be replaced by the more practicable CHARTWEEL (CHART-weekend less). PROTOCOL OF THE TRIAL: A randomized multicenter trial of definite radiotherapy in locally advanced inoperable NSCLC was designed (ARO 97-1, Arbeitsgemeinschaft Radioonkologie der Deutschen Krebsgesellschaft). Conventional fractionation to 66 Gy (5 weekly fractions of 2 Gy) is compared with CHARTWEEL to 60 Gy (15 weekly fractions of 1.5 Gy, Monday to Friday, interval between fractions > or = 6 hours, overall treatment time 2.5 weeks). The main endpoint of the trial is overall survival. It was calculated that an entry of 665 patients is needed to detect an improvement in 2-year survival of 10%, the actual time is estimated to be 5 years or less. The trial was activated on 1.9.1997.

Adult↗

Inverse radiotherapy planning for a concave-convex PTV in cervical and upper mediastinal regions. Simulation of radiotherapy using an Alderson-RANDO phantom. Planning target volume.

AIM: Three-dimensional inverse treatment planning with modulated beams was applied for dosimetric optimization of a lengthy (22 cm) and complex (concave-convex) shaped planning target volume (PTV) in the cervical and upper mediastinal regions. MATERIAL AND METHOD: The planning was done for 9 coplanar beams spaced evenly at 40 intervals. Properties of 15 MV photons from a linear accelerator were simulated. The optimization of the fluence modulation profiles for each beam was based on a definition of the desired/permitted relative dose levels in the PTV and organs at risk, and a definition of the strengths of the constraints to achieve these objectives. RESULTS: An adequate dose delivery to the PTV and protection of the spinal cord are completely achievable. The dose delivered to the lungs is clinically acceptable with respect to the risk of radiation-induced pneumonitis. For reasons of physics, no further decrease in the radiation burden on the lungs can be attained with X-rays without compromising the PTV coverage. The radiation burden on some critical part of normal tissues was effectively reduced by application of a dummy organ at risk. CONCLUSION: The inverse planning is an effective method for conformal radiotherapy of large tumors as well. However, the power of the technique is insufficient when the tolerance dose of the neighbouring normal tissue is too low and its volume effect is high. Although requiring further operator interactions, introduction of dummy organs at risk may be of help in reducing the radiation burden on normal tissues.

Body Burden↗

The development of quality assurance programs for radiotherapy within the German Hodgkin Study Group (GHSG). Introduction, continuing work, and results of the radiotherapy reference panel.

BACKGROUND AND PURPOSE: The German Hodgkin Study Group (GHSG), including more than 500 participating centers, established a central radiotherapy (RT) reference center to improve quality of treatment, starting with the first study generation in 1978. More than 11,000 patients with Hodgkin's lymphoma (HL) have been enrolled into these trials. Extensive continuing quality assurance programs (QAPs) during the study generations have been performed. The purpose of the present article is to summarize the experiences and results of the performed and ongoing QAPs. MATERIAL AND METHODS: A panel of expert radiation oncologists (second study generation HD4-6, 1988-1994, and third study generation HD7-9, 1993-1998) retrospectively evaluated the adequacy of treatment fields, applied radiation doses, treatment time, and technical parameters. Furthermore, a detailed analysis of relapses in correlation with the performed RT was conducted. For the fourth study generation (HD10-12, 1998-2002), the RT reference center changed from Munich to Cologne. New RT QAPs were initiated according to the demands of the new trials and former programs were enhanced: (1) central prospective radiation oncologic review of cross-sectional imaging (HD10, HD11) to create the individual radiation treatment plan; (2) retrospective analysis of the adequacy of the performed involved-field (IF) RT (HD10, HD11); (3) the multidisciplinary HD12 panel (radiation oncologists, medical oncologists, diagnostic radiologists); (4) initiation and integration of a teleradiotherapy network into the GHSG trials. RESULTS: A strong achievement of these activities in the era of extended-field RT was to show that major deviations of radiation treatment portals and radiation dose from prospective treatment prescriptions revealed to be unfavorable prognostic factors for patients with early-stage HL (HD4). The central prospective radiation oncological review of all diagnostic imaging (HD10, HD11) showed that corrections of disease involvement in 49% of patients (593/1,214) with early stages (HD10) and in 67% of patients (936/1,397) with intermediate stages (HD11) were necessary. These procedures had a significant impact on the correctness of stage definition, allocation to treatment groups and on the extension of the IF treatment volume. Until now, 1,080 patients in HD10 and HD11 have been evaluated retrospectively with regard to the adequacy of the performed IF-RT. Although the participating institutions got a precise RT prescription, interim results reveal deviations in a significant number of cases. In the HD12 trial (advanced stages), a multidisciplinary panel of radiation oncologists, radiologists and medical oncologists reviewed all the diagnostic imaging from diagnosis throughout the treatment in comparison to the documentation forms. For patients with poor response to chemotherapy, the panel recommended RT independent of the randomization. This procedure ensured that patients with a poor response to chemotherapy received additional RT. 1,080 of 1,594 randomized patients (68%) could be analyzed. After chemotherapy, 599 patients (56%) showed residual disease (> 1.5 cm), and in 145/1,080 patients (13.5%) the panel recommended additional RT independent of the randomization arm. The introduction of electronic image transfer optimized and simplified the workflow of the QAPs. Rapid online consultation and real-time teleconferences regarding disease involvement, patient management and communication of the RT prescription with connected hospitals proved to be extremely helpful. CONCLUSION: Today, radiation oncologists in the GHSG perform a continuous and efficient QAP to improve treatment quality of study patients. For early favorable and unfavorable HL a central prospective review of all diagnostic imaging is performed by expert radiation oncologists to control the disease extension and to define the IF treatment volume. Retrospective analysis of RT portals by an expert panel detects faults in the applied irradiation. Participants are trained on the definition of IF-RT by workshops on the occasion of annual GHSG meetings and on the annual meetings of the German Society of Therapeutic Radiation Oncology (DEGRO). For the advanced stages a multidisciplinary panel evaluates the treatment response to chemotherapy. Patients with a poor response receive additional RT due to the panel's recommendation. The introduction of teleradiotherapy into the GHSG trials improves the dialogue between the central RT reference center and study participants and thus contributes to high RT quality for study patients.

Disease-Free Survival↗

Radiotherapy for muscle-invasive carcinoma of the bladder: results of a randomized trial comparing conventional whole bladder with dose-escalated partial bladder radiotherapy.

PURPOSE: To investigate whether delivering an increased radiation dose to the tumor-bearing region of the bladder alone would improve local disease control without increasing treatment toxicity. METHODS AND MATERIALS: A total of 149 patients with unifocal T2-T3N0M0 bladder carcinoma were randomized between whole bladder conformal radiotherapy (WBRT, 52.5 Gy in 20 fractions, n = 60) and partial bladder conformal RT (PBRT) to tumor alone with 1.5-cm margins within either 4 weeks (PBRT4, 57.5 Gy in 20 fractions, n = 44) or 3 weeks (PBRT3, 55 Gy in 16 fractions, n = 45). The response was assessed cystoscopically after 4 months. RESULTS: The 5-year overall and CFS rate was 58% and 47%, respectively, for the whole population. The CR rate was 75% for WBRT, 80% for PBRT4, and 71% for PBRT3 (p = 0.6), with a 5-year local control rate of 58%, 59%, and 34%, respectively (p = 0.18). Solitary new tumors arose within the bladder, outside the irradiated volume, in 6 (7%) of 89 patients who underwent PBRT. The 5-year overall survival and cystectomy-free survival rate was 61% and 49% for WBRT, 60% and 50% for PBRT4, and 51% and 41% for PBRT3 (p = 0.81 and p = 0.59). The treatment toxicity was mild and equivalent across the three trial arms. CONCLUSION: The reduction in treatment volume allowed delivery of an increased radiation dose without a reduction in local tumor control or the development of excess toxicity. However, this dose-escalated partial bladder approach did not result in significantly improved overall survival.

Adult↗

Comparison of adjuvant versus salvage radiotherapy policies for postprostatectomy radiotherapy.

PURPOSE: We compared the long-term results of postprostatectomy radiotherapy (RT) from two institutions, one adapting a prospective policy of adjuvant RT and the other salvage RT. METHODS AND MATERIALS: Between 1989 and 1997, 69 patients were referred for adjuvant RT to the institution using adjuvant RT and 88 patients with evidence of recurrence were treated in the institution using salvage RT. The salvage group underwent RT after longer postoperative intervals (median, 40.3 vs. 2.9 months; p <0.0001) and had higher prostate-specific antigen (PSA) values before starting RT (4.5 vs. 0.86 ng/mL; p = 0.003). Both groups were routinely treated to a minimal total dose of 60 Gy. The treatment groups were analyzed for overall survival, disease-specific survival, distant metastasis-free survival, and biochemical recurrence-free survival (BRFS) using Cox proportional hazards modeling. RESULTS: Of the 69 patients referred for adjuvant RT, 22 (32%) had nonzero PSA values before RT. Multivariable modeling of BRFS found only the PSA value before RT to be statistically significant (p <0.0001). RT after prostatectomy was equally effective in either setting when the pre-RT PSA level was <1 ng/mL. When the PSA value before RT was >or=1 ng/mL, the 5-year BRFS for each group was inferior. CONCLUSION: Although the adjuvant treatment policy was associated with significantly improved BRFS, this was attributable to low pre-RT PSA values. When the treatment groups were stratified for pre-RT PSA level, the differences in BRFS were not statistically significant. Patients with a rising PSA level after prostatectomy, regardless of their initial risk, should receive prompt referral for RT.

Adenocarcinoma↗

Feasibility of synchronization of real-time tumor-tracking radiotherapy and intensity-modulated radiotherapy from viewpoint of excessive dose from fluoroscopy.

PURPOSE: Synchronization of the techniques in real-time tumor-tracking radiotherapy (RTRT) and intensity-modulated RT (IMRT) is expected to be useful for the treatment of tumors in motion. Our goal was to estimate the feasibility of the synchronization from the viewpoint of excessive dose resulting from the use of fluoroscopy. METHODS AND MATERIALS: Using an ionization chamber for diagnostic X-rays, we measured the air kerma rate, surface dose with backscatter, and dose distribution in depth in a solid phantom from a fluoroscopic RTRT system. A nominal 50-120 kilovoltage peak (kVp) of X-ray energy and a nominal 1-4 ms of pulse width were used in the measurements. RESULTS: The mean +/- SD air kerma rate from one fluoroscope was 238.8 +/- 0.54 mGy/h for a nominal pulse width of 2.0 ms and nominal 100 kVp of X-ray energy at the isocenter of the linear accelerator. The air kerma rate increased steeply with the increase in the X-ray beam energy. The surface dose was 28-980 mGy/h. The absorbed dose at a 5.0-cm depth in the phantom was 37-58% of the peak dose. The estimated skin surface dose from one fluoroscope in RTRT was 29-1182 mGy/h and was strongly dependent on the kilovoltage peak and pulse width of the fluoroscope and slightly dependent on the distance between the skin and isocenter. CONCLUSION: The skin surface dose and absorbed depth dose resulting from fluoroscopy during RTRT can be significant if RTRT is synchronized with IMRT using a multileaf collimator. Precise estimation of the absorbed dose from fluoroscopy during RT and approaches to reduce the amount of exposure are mandatory.

Calibration↗

Proton beam radiotherapy versus fractionated stereotactic radiotherapy for uveal melanomas: A comparative study.

PURPOSE: A comparative treatment planning study was undertaken between proton and photon therapy in uveal melanoma to assess the potential benefits and limitations of these treatment modalities. A fixed proton horizontal beam (OPTIS) and intensity-modulated spot-scanning proton therapy (IMPT), with multiple noncoplanar beam arrangements, was compared with linear accelerator-based stereotactic radiotherapy (SRT), using a static and a dynamic micromultileaf collimator and intensity-modulated RT (IMRS). METHOD AND MATERIALS: A planning CT scan was performed on a brain metastasis patient, with a 3-mm acquisition slice spacing and the patient looking at a luminous spot with the eyes in three different positions (neutral and 25 degrees right and left). Four different gross tumor volumes were defined for each treatment technique. These target scenarios represented different locations (involving vs. not involving the macula and temporal vs. nasal) and volumes (10 x 6 mm vs. 16 x 10 mm) to challenge the proton and photon treatment techniques. The planning target volume was defined as the gross tumor volume plus 2 mm laterally and 3 mm craniocaudally for both modalities. A dose homogeneity of 95-99% of the planning target volume was used as the "goal" for all techniques. The dose constraint (maximum) for the organs at risk (OARs) for both the proton and the SRT photon plans was 27.5, 22.5, 20, and 9 CGE-Gy for the optic apparatus, retina, lacrimal gland, and lens, respectively. The dose to the planning target volume was 50 CGE-Gy in 10 CGE-Gy daily fractions. The plans for proton and photon therapy were computed using the Paul Scherrer Institute and BrainSCAN, version 5.2 (BrainLAB, Heimstetten, Germany) treatment planning systems, respectively. Tumor and OARs dose-volume histograms were calculated. The results were analyzed using the dose-volume histogram parameters, conformity index (CI(95%)), and inhomogeneity coefficient. RESULTS: Target coverage of all simulated uveal melanomas was equally conformal with the photon and proton modalities. The median CI(95%) value was 1.74, 1.86, and 1.83 for the static, dynamic, and IMSRT plans, respectively. With proton planning, the median CI(95%) was 1.88 for OPTIS and substantially improved with IMPT in some tumor cases (median CI(95%), 1.29). The tumor dose homogeneity in the proton plans was, however, always better than with SRT photon planning (median inhomogeneity coefficient 0.1 and 0.15 vs. 0.46, 0.41, and 0.23 for the OPTIS and IMPT vs. the static, dynamic, and IMSRT plans, respectively). Compared with the photon plans, the use of protons did not lead to a substantial reduction in the homolateral OAR total integral dose in the low- to high-dose level, except for the lacrimal gland. The median maximal dose and dose at the 10% volume with the static, dynamic, and IMSRT plans was 33-30.8, 31.8-28, and 35.8-49 Gy, respectively, for the lacrimal gland, a critical organ. For protons, only the OPTIS plans were better, with a median maximal dose and dose at the 10% volume using OPTIS and IMPT of 19.2 and 8.8 and 25.6 and 23.6 CGE, respectively. The contralateral OARs were completely spared with the proton plans, but the median dose delivered to these structures was 1.2 Gy (range, 0-6.3 Gy) with the SRT photon plans. CONCLUSION: These results suggest that the use of SRT photon techniques, compared with protons, can result in similar levels of dose conformation. IMPT did not increase the degree of conformality for this small tumor. Tumor dose inhomogeneity was, however, always increased with photon planning. Except for the lacrimal gland, the use of protons, with or without intensity modulation, did not increase homolateral OAR dose sparing. The dose to all the contralateral OARs was, however, completely eliminated with proton planning.

Brain Neoplasms↗

Audit of the radiotherapy in the DBCG 82 b&c trials--a validation study of the 1,538 patients randomised to postmastectomy radiotherapy.

INTRODUCTION: In the DBCG 82 b&c trials 3083 patients with stages II and III breast cancer were randomised to receive postmastectomy radiotherapy (RT) versus no RT in addition to systemic therapy. The study showed a decrease in loco-regional recurrences and an improved survival in patients receiving RT. The aim of the present study was to describe the delivered RT for the 1538 patients who were randomised to RT, and to evaluate the compliance with the RT guidelines. PATIENTS AND METHODS: Basic information about the given RT was recorded in the DBCG data centre. For the current study, missing and additional information was collected from individual RT treatment charts. We defined some criteria for complying with the DBCG RT guidelines regarding target coverage and dose and fractionation and based on that we also defined some criteria for having clinically acceptable RT treatments. RESULTS: Of the 1538 patients, 87% received megavoltage RT, 8% had orthovoltage RT and 5% never began or completed RT. Of the 1341 megavoltage irradiated patients, the guideline compliance regarding target coverage of the axillary/periclaviculary region, internal mammary nodes and chest wall was 88, 79 and 85%, respectively. Only 0, 0.2 and 0.4% did not have clinically acceptable target coverage. The dose and fractionation was according to the guidelines in 96% and none had clinically unacceptable dose and fractionation schedules. CONCLUSION: The guideline compliance for megavoltage RT was high with 88, 79 and 85% complying with the guidelines regarding target coverage of the axillary/periclaviculary region, internal mammary nodes and chest wall, respectively, and with 96% complying with the guidelines regarding dose and fractionation schedules. Less than 1% had clinically unacceptable target coverage and none had unacceptable dose and fractionation schedules.

Adult↗

Clinical results of retreatment of vertebral bone metastases by stereotactic conformal radiotherapy and intensity-modulated radiotherapy.

PURPOSE: Reirradiation of spinal tumors is limited by the tolerance of the spinal cord. We evaluated local control, pain relief, neurologic improvement, side effects, and survival rates after fractionated conformal radiotherapy (FCRT) and intensity-modulated RT (IMRT) of recurrent spinal metastases. METHODS AND MATERIALS: Eighteen patients with 19 radiologic manifestations were retreated for recurrent spinal metastases using FCRT (n = 5) or IMRT (n = 14). All patients had previously undergone conventional RT (median dose 38 Gy). The indication for reirradiation was tumor progression associated with pain (n = 16) or neurologic symptoms (n = 12). The median time to recurrence was 17.7 months. The median total dose for reirradiation was 39.6 Gy. RESULTS: The overall local control rate was 94.7% after a median follow-up of 12.3 months. Of 16 patients with pain, 13 experienced significant relief after reirradiation. Neurologic improvement was obtained in 5 of 12 patients. Tumor size remained unchanged in 84.2%. A partial response was seen in 2 of 19 patients. One patient had local tumor progression 9.5 months after reirradiation. Six patients received chemotherapy after reirradiation because of progressive distant metastases. Twelve patients died 10.5 months median after reirradiation. No clinically significant late toxicity was seen after FCRT or IMRT. CONCLUSION: These data demonstrate that FCRT and IMRT are effective and safe in recurrent spinal tumors and can be offered to patients to achieve local control, as well as pain relief.

Female↗

Breast-conserving treatment with or without radiotherapy in ductal carcinoma-in-situ: ten-year results of European Organisation for Research and Treatment of Cancer randomized phase III trial 10853--a study by the EORTC Breast Cancer Cooperative Group and EORTC Radiotherapy Group.

PURPOSE: The European Organisation for Research and Treatment of Cancer conducted a randomized trial investigating the role of radiotherapy (RT) after local excision (LE) of ductal carcinoma-in-situ (DCIS) of the breast. We analyzed the efficacy of RT with 10 years follow-up on both the overall risk of local recurrence (LR) and related to clinical, histologic, and treatment factors. PATIENTS AND METHODS: After complete LE, women with DCIS were randomly assigned to no further treatment or RT (50 Gy). One thousand ten women with mostly (71%) mammographically detected DCIS were included. The median follow-up was 10.5 years. RESULTS: The 10-year LR-free rate was 74% in the group treated with LE alone compared with 85% in the women treated by LE plus RT (log-rank P < .0001; hazard ratio [HR] = 0.53). The risk of DCIS and invasive LR was reduced by 48% (P = .0011) and 42% (P = .0065) respectively. Both groups had similar low risks of metastases and death. At multivariate analysis, factors significantly associated with an increased LR risk were young age (< or = 40 years; HR = 1.89), symptomatic detection (HR = 1.55), intermediately or poorly differentiated DCIS (as opposed to well-differentiated DCIS; HR = 1.85 and HR = 1.61 respectively), cribriform or solid growth pattern (as opposed to clinging/micropapillary subtypes; HR = 2.39 and HR = 2.25 respectively), doubtful margins (HR = 1.84), and treatment by LE alone (HR = 1.82). The effect of RT was homogeneous across all assessed risk factors. CONCLUSION: With long-term follow-up, RT after LE for DCIS continued to reduce the risk of LR, with a 47% reduction at 10 years. All patient subgroups benefited from RT.

Adult↗

Radical radiotherapy for carcinoma of the uterine cervix using external beam radiotherapy and a single line source brachytherapy technique: the Clatterbridge technique.

At the Clatterbridge Centre for Oncology, a single line source brachytherapy technique using the Selectron (Nucletron) low dose rate remote afterloading equipment has been developed for use in conjunction with homogenous whole pelvis external beam radiotherapy in the radical treatment of carcinoma of the cervix. The technique incorporates several modifications aimed at reducing treatment related morbidity while maintaining satisfactory local tumour control and cure rates. A flexible dose prescription system has been devised to allow individualization of the brachytherapy isodose distribution according to the clinical findings and the estimated normal tissue doses. Modifications of source loading distributions are carried out to limit the point "A" dose rate to a narrow range to take into account the dose rate effect on the risk of complications. Source loading distributions are also modified according to the estimated normal tissue doses in order to respect normal tissue tolerance. This paper describes the technique and its underlying principles.

Brachytherapy↗

[Mathematical modeling of optimal dose fields in radiotherapy of malignant tumors. Part 2 (Contact methods of radiotherapy)].

The principles of mathematical modeling of optimal dose fields in contact radiotherapy (RT) of malignant tumors are investigated. The point dose additivity provides for presetting the permissible dose field in an irradiated organism as a system of linear limitations to doses in the control points (CP) distributed in the lesion focus and in healthy organs and tissues. It was shown as impossible to shape a dose field by linear limitations to doses in CP in using the RT contact methods with the irradiation sources being implanted into lesion focus. A mathematic interpretation was suggested for the task (with its solution by an iterative algorithm) of forming an optimal dose field in the lesion focus with implanted irradiation sources, which is based on maximizing the factor of dose-field homogeneity. It was further demonstrated that linear limitations, if added to the dose in healthy organs and tissues, make the task even more complicated if not insoluble. Finally, it is suggested to use the method of shaping an effective dose field by the iterative method with interactive visual optimization of the dose field.

Algorithms↗

Integration of intraoperative radiotherapy (IORT) dose distribution into the postoperative CT-based external beam radiotherapy (EBRT) treatment planing.

In the treatment of malignant disease external beam radiation therapy (EBRT) is often combined with surgery. Intraoperative radiotherapy (IORT) improves the local control by dose escalation. For reasons of recording, improvement and security of the intervention, it would be necessary to merge the IORT-dose distribution with the postoperative CT-based EBRT-planing. The aim of this work was to develop a method to reconstruct the IORT field and register it with the postoperative planing CT. This enables the reconstruction of the IORT dose distribution and merge it with the CT-based EBRT planing data. We use a surface scanner to receive a large amount of surface points which enables us reconstruct the IORT-field and to register it with the CT-based EBRT planning data. Scanning and calculation time is not over 2 seconds, depending mainly on the CPU power. The error of a single point is below 1 mm. The density of the point cloud is approx. 4 per mm2. In this paper we give an overview of our experimental setup and the accuracy of the method.

Brachytherapy↗

Comparison of systemic radiotherapy with I-131-labeled monoclonal antibody BW575/9 to external beam radiotherapy in human neuroblastoma xenografts.

The therapeutic effectiveness of external beam radiotherapy (XRT) and radioimmunotherapy (RIT) was investigated in a human neuroblastoma (SK-N-SH) xenotransplanted to nude mice. This tumor model seems especially suitable for comparison of the relative biological effectiveness of RIT vs. XRT, as--in contrast to most tumor models--it shows an unusually homogenous uptake of the labeled MAb, thus providing a homogenous intratumoral dose distribution. XRT was performed using single fractions of 800, 1600, 2000 and 2400 cGy and RIT was delivered by intravenous injection of 15, 19 and 26 MBq of the I-131-labeled monoclonal antibody (MAb) BW575/9. Therapeutic efficiency of the two radiation modalities was assessed in terms of tumor volume doubling time (VDT). Miniature thermoluminescent (mini-TLD) dosimetry and MIRD-based dose calculations were used to evaluate the absorbed doses delivered by RIT and to assess the degree of homogeneity of the dose distribution. RIT with 19 MBq of the I-131 BW575/9 delivered a tumor dose of 2820 cGy measured by TLD and resulted in a tumor VDT of 32 days (vs. one day in controls). An equivalent effect on VDT was achieved by a single fraction XRT of 1600 cGy. The relative efficiency of XRT compared with RIT (ratio of dose XRT/dose RIT required to give the same VDT) was 0.57. Application of 26 MBq of the MAb (= 3200 cGy) resulted in complete tumor regression after ten days as did XRT with 2400 cGy, corresponding to a relative efficiency of 0.75.

Animals↗

Radiotherapy and neoadjuvant chemotherapy for cervical carcinoma. A randomized multicenter study of sequential cisplatin and 5-fluorouracil and radiotherapy in advanced cervical carcinoma stage 3B and 4A.

BACKGROUND: The locoregional failure rate remains high in advanced cervical carcinoma. Chemotherapy (CT) was added to radiotherapy (RT) in order to increase disease control and to improve 5-year survival. METHODS: CT + RT included cisplatin administered 100mg/m2, d.1 plus 5-fluorouracil 1000 mg/m2 D.1 to 5, ci (120 hrs), q every 3rd week for 3 cycles, followed by RT. RT included external beam irradiation 64.8 Gy in 1.8 Gy fractions, five days a week, by 4-field box technique. The median follow-up was 46 months. Ninety-four patients were evaluable for survival, 47 in the CT + RT group and 47 in the RT group. Ninety-two patients were evaluable for response. Known prognostic factors were equally distributed between the two groups. RESULTS: Of the 43 patients evaluable before RT, 31 (72%) achieved a partial or complete response after CT alone. After RT, 52 patients attained a complete response, 25 in the CT + RT group and 27 in the RT-group. Sixty-three patients developed distant metastases or local relapse, 30 in the CT + RT group and 33 in the RT group. In the CT + RT group 6 of the 9 patients with metastases also had local progression at relapse, in the RT group, 7 of 17 patients. The survival rates for the two groups are not statistically different. Thirty-seven patients are alive, 29 have no evidence of disease. Fifty-seven have died, 29 in the CT + RT group and 28 in the RT group. Fifty-four deaths were related to cancer, and 3 to therapy. CONCLUSIONS: Sequential CT and RT did not improve the survival, local control, or metastasis rate compared with RT alone.

Adult↗

Second malignant neoplasms in patients treated for Hodgkin's disease with radiotherapy or radiotherapy and chemotherapy.

The incidence of second malignant neoplasms (SMN) was assessed in 248 patient with Hodgkin's disease (HD) treated by radiotherapy alone (XRT) or in combination with chemotherapy (XRT + C) between January/1960 and June/1977. Radiation therapy was categorized as less than extended field (less than EF), extended field (EF) or total nodal irradiation (TNI). Chemotherapy was scored as single agent (SAC) or multiagent (MAC). MAC consisted primarily of either nitrogen mustard, vincristine, prednisone and procarbazine (MOPP) or cyclophosphamide, vinblastine, procarbazine and prednisone (CVPP). Ten metachronous malignancies occurred 1-21 years (median 10 years) after the diagnosis of HD. With a median follow-up of 6 years the observed-to-expected ratio (O/E) was 4.2 for XRT alone and 7.6 for XRT + MAC. For 46 patients with greater than or equal to 10 years follow-up (median 13 years) the O/E ratio was 16.1 for XRT and 26.5 for XRT + MAC. All SMN occurred in patients who had not had a splenectomy at or prior to the time of HD diagnosis. Only four of nine solid SMN were within treatment portals or near portal margins. The diagnosis of another malignant neoplasm was made prior to or simultaneous with the diagnosis of HD in four additional patients. This observation, and the occurrence of five of six SMN outside of the treatment field in the XRT alone group, suggest that there may be factor(s) associated with the incidence of SMN in HD in addition to treatment itself.

Adolescent↗

A randomized study of radiotherapy versus radiotherapy plus chemotherapy in stage I-II non-Hodgkin's lymphomas.

In a randomized, prospective trial from 1974-1978, 73 patients with non-Hodgkin's lymphomas in clinical Stage I or II were treated with extended field radiotherapy alone (RT) or RT plus adjuvant chemotherapy with vincristine, streptonigrin, cyclophosphamide and prednisone (RT + CT). With a median follow-up time of five years, 54% have relapsed in the RT group versus only 10% in the RT + CT group (P less than 0.01). There is no statistical difference in the overall survival yet, but 13/14 deaths in the RT group versus only 3/12 in the RT + CT group were due to progressive disease. Among patients with unfavorable histology, 13/22 in the RT group have died from disease progression against 3/34 in the RT + CT group (P less than 0.01). The results are in agreement with those from two other series published in detail. Based on these results we therefore recommend to use adjuvant CT with RT in all Stage I-II patients with unfavorable histology. Further observation is necessary before a conclusion can be drawn for the lymphoma patients with more favorable histology.

Antineoplastic Agents↗

Comparison of postoperative radiotherapy and combined postoperative radiotherapy and chemotherapy in the multidisciplinary management of malignant gliomas. A joint Radiation Therapy Oncology Group and Eastern Cooperative Oncology Group study.

Recently, the RTOG and ECOG concluded a joint randomized study on malignant gliomas that was in progress for the past five years. A total of 626 patients entered this protocol. Sixty-seven percent of the 535 evaluable patients have died and thus this represents a preliminary report of a major joint clinical trial. The objective of this study was to evaluate the efficacy after neurosurgery of three new treatment options as compared with control treatment of radiotherapy alone. The four options were: (1) control radiation; 6000 rad/6-7 weeks to whole brain; (2) a higher radiation dose; Control dose plus a booster dose of 1000 rad/1-2 weeks to the tumor; (3) control radiation dose plus BCNU (80 mg/m2/day IV X 3 and repeat BCNU every 8 weeks); (4) Control radiation dose plus combination methyl-CCNU (125 mg/m2/day orally X 1 and repeat methyl-CCNU every 8 weeks), and DTIC (150 mg/m2/day IV X 5 and repeat DTIC every 4 weeks). All pertinent patient characteristics were studied and several important prognostic factors have been identified. Notably, age, histologic type (Astrocytoma with anaplastic foci, versus glioblastoma multiforme), initial performance status, time since first symptoms and presence or absence of seizure. At this time, it appeared that there was no treatment option which was significantly better than the control. The study identified that age was the most important prognostic factor. Patients who were younger than age 40 years had an 18-month survival of 64%, patients who were age 40-60 years had an 18-month survival of 20%, and patients who were older than age 60 had an 18-month survival of 8%. The study also demonstrated that a modified histologic classification of anaplastic astrocytoma versus glioblastoma provided better prognostic information than the astrocytoma grading system of Kernohan. Patients with anaplastic astrocytoma had a median survival of 27 months as compared to 8 months for patients with glioblastoma. In further evaluation of any beneficial effect of chemotherapy, it was identified that only among the 40-60-year-old groups, BCNU treated patients appeared to have significantly increased survival than patients in the control groups (P = 0.01, one-sided). Similarly, methyl-CCNU + DTIC was suggestively better than the control (P = 0.08, one-sided). The higher radiation dose, 7000 rad/8-9 weeks appeared to give no significantly better survival over the control dose option. Both BCNU and methyl-CCNU + DTIC produced some toxicity. The combination of methyl-CCNU + DTIC was more toxic than BCNU, producing severe or worse thrombocytopenia in 23% of the patients as compared to 6% on BCNU.

Adult↗