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Editor's note
In:. 1. Radiation Oncol. Bid. Phys.. Vol. 9. No. 9. pp. 1253-1254, Pergamon Press Ltd. Printed in the U.S.A.
1983
All rights reserved.
EDZTOR'SNOTE The treatment of anal carcinoma, generally considered in the domain of the surgeon, is being challenged by radiation oncology investigators. Cantril, Green, Stall and Schaupp report 80% of the patients treated by irradiation alone have remained locally controlled and for favorable N, patients, the 5-year survival is 95%. This result allows for anal preservation and the avoidance of mutilating surgery as abdomino-pereneal resections. The rate of severe radiation complications, such as necrosis and ulceration, was only 12% with doses averaging 6500 cGy and is much lower than other reports in the literature. The new, exciting development in clinical trials for anal cancer is addressed in the editorial by Cummings, who is exploring combined modality therapy with radiation dose reduction. Building on reports of other investigators, such as Nigor et al, Sischy et al, and their own experience with 5 FU and mitomycin C infusion during irradiation, a higher tumor clearance and primary tumor sterilization has been found with doses ranging from 3000 to 5000 cGy. This has led to a new generation of alimentary tract protocols from anus to esophagus, in which this research theme isbeing actively studied in national cooperative groups, both with and without limited surgical excision. One other important observation is high incidence of ano-receptive homosexuals in this series and the need to disseminate this information for the purpose of preventive oncology. To better understand etiologies, the radiation oncologist can assist in pointing to epidemiologic investigation by obtaining more detailed sexual histories on patients. The final answer as to the value and place of fast neutron therapy in radiation oncology practice will need more study. In this issue, there is an encouraging report by Griffin et al of an RTOG study showing a higher clearance and complete response rate for metastatic cervical nodes, adenopathy for mixed neutron/photon schedules versus photon irradiation alone. The 2-year, disease-free survival is 46% versus 33% for all nodal stages combined (N,, N,, NJ which was significant with ap value of 2 0.03. The clearance rate of cervical adenopathy is correlated with longer patient survival. A possible reason for metastatic nodes being a good model for tumor hypoxia and a test site for neutron therapy versus photons is the common observation on CT of central necrosis in such nodes. Two other reports by Maor et al update the MDAH-TAMVEC pilot and randomized head and neck cancer neutron trial. No significant difference in local-regional tumor control was found between neutron beam, mixed beam patients, as compared to either neutrons or photon beams only, for comparable survival in their pilot study. However, in their randomized study, using an actuarial analysis, a superior, local control rate and survival rate were found for advanced head and neck cancer, as compared to massive disease for mixed beam irradiation over conventional photon schedules in the first two years without differences in complications. In his editorial on this subject, Fowler offers sound reasons for waiting a few years before “throwing our caps over the cyclotron” and emphasizes the need for currently planned trials of fast neutron therapy versus megavoltage therapy by installing a neutron machine in medical centers which can compete with good penetrating beams and geometry, as are generated by state-of-the-art, high energy linear accelerators. Although neutron therapy has been shown to be very effective in eradicating gross salivary gland tumors, the excellent results achieved by a mixed photon and electron schedule; in the postoperative setting where there is minimum residuum and the major portion of the tumor has been excised, is reported by McNaney et al. A local-regional control rate of 87% was achieved and the authors argue for facial nerve preservation, if it is not grossly involved. The isodose curves for 20 MV photons and 18 MV electrons provide excellent coverage of the tumor bed with a minimum complication rate. Also in this issue, is a state-of-the-art report by Tadros et al on the ability of total skin electron irradiation to control mycoses fungoides. Despite delivering doses of 3000 cGy with 3 MV electrons and a 5-year actuarial survival of 66.7%, only a disease-free survival of 21.4% was achieved. As anticipated, an early stage patient with Tt Tz Na disease has frequent, complete responses and better relapse-free survival than advanced states. Although patterns of failure were predominantly in sites of previous involvement, extracutaneous dissemination was a frequent cause of death. Attention to radiation technique is essential, with need to provide dose homogeneity and particular attention to shielding. Although the radiation dose was an important determinant in outcome; higher doses, according to the authors, were not possible without increasing the morbidity of the acute skin reaction. Although tumor masses due to incomplete beam penetration may be an explanation for common relapse in skin, the frequency of dissemination of circulating T cells argues for new approaches with systemic agents, such as the addition of chemotherapy as adjuvants to improve results, particularly in advanced stages of this disease where total skin electron irradiation by itself is of limited effectiveness. A variety of other subjects are of interest and include late effects of radiation and chemotherapy. The increase in bone marrow activity in protected, unirradiated sites after extended field therapy has been documented by Parmeatier et al. This compensatory mechanism allows for return of peripheral blood counts shortly after treatment and persists for years. The liver complications reported by Haddad et al add adriamycin and CCNU to active agents that enhance untoward liver effects and the need for dose reduction to the 10 Gy level to be within tolerance. Elevations of liver enzymes, veno-occlusive disease, hepatomegaly and ascites have all been noted to occur, but the importance of biopsy confirmation is stressed.
1253
1254
Editor’s Note
In the report by Littman et al, dealing with soft tissue sarcomas of the head and neck in children, radiotherapy and combination chemotherapy proved successful for a 75% 5-year survival rate. Although various complications were encountered, few were so severe as not to recommend the current program of management. Their observation of the benefit of total cranial irradiation, where the base of the skull is involved, is strongly suggested by the extensive meningeal invasion that occurred when parameningeal CT changes were noted. Tef’ft, in his editorial, indicates the importance of maintaining quality of research at a single institution in clinical trials and how it reinforces the achievements and results of intergroup national trials. An important topic is the Oncology Intelligence offering, “The Flexure Dose” by Tucker and Thames, which is defined “as the largest fractional dose for which further fractionation produces no significant change in total dose required to reach a specific effect level.” The flexure dose is defined as a multiple of CX//~ of the parameters in the linear quadratic model of cell survival and estimates are offered for a large variety of normal and neoplastic tissues. The dissociation between acute and late radiation effects, often hyperfractionation, can be explained on the basis of a flexure dose for late reacting tissues that is smaller than that for tumors and acutely responding tissues. PHILIP RUBIN, M.D. Editor-in-Chief
1983
All rights reserved.
EDZTOR'SNOTE The treatment of anal carcinoma, generally considered in the domain of the surgeon, is being challenged by radiation oncology investigators. Cantril, Green, Stall and Schaupp report 80% of the patients treated by irradiation alone have remained locally controlled and for favorable N, patients, the 5-year survival is 95%. This result allows for anal preservation and the avoidance of mutilating surgery as abdomino-pereneal resections. The rate of severe radiation complications, such as necrosis and ulceration, was only 12% with doses averaging 6500 cGy and is much lower than other reports in the literature. The new, exciting development in clinical trials for anal cancer is addressed in the editorial by Cummings, who is exploring combined modality therapy with radiation dose reduction. Building on reports of other investigators, such as Nigor et al, Sischy et al, and their own experience with 5 FU and mitomycin C infusion during irradiation, a higher tumor clearance and primary tumor sterilization has been found with doses ranging from 3000 to 5000 cGy. This has led to a new generation of alimentary tract protocols from anus to esophagus, in which this research theme isbeing actively studied in national cooperative groups, both with and without limited surgical excision. One other important observation is high incidence of ano-receptive homosexuals in this series and the need to disseminate this information for the purpose of preventive oncology. To better understand etiologies, the radiation oncologist can assist in pointing to epidemiologic investigation by obtaining more detailed sexual histories on patients. The final answer as to the value and place of fast neutron therapy in radiation oncology practice will need more study. In this issue, there is an encouraging report by Griffin et al of an RTOG study showing a higher clearance and complete response rate for metastatic cervical nodes, adenopathy for mixed neutron/photon schedules versus photon irradiation alone. The 2-year, disease-free survival is 46% versus 33% for all nodal stages combined (N,, N,, NJ which was significant with ap value of 2 0.03. The clearance rate of cervical adenopathy is correlated with longer patient survival. A possible reason for metastatic nodes being a good model for tumor hypoxia and a test site for neutron therapy versus photons is the common observation on CT of central necrosis in such nodes. Two other reports by Maor et al update the MDAH-TAMVEC pilot and randomized head and neck cancer neutron trial. No significant difference in local-regional tumor control was found between neutron beam, mixed beam patients, as compared to either neutrons or photon beams only, for comparable survival in their pilot study. However, in their randomized study, using an actuarial analysis, a superior, local control rate and survival rate were found for advanced head and neck cancer, as compared to massive disease for mixed beam irradiation over conventional photon schedules in the first two years without differences in complications. In his editorial on this subject, Fowler offers sound reasons for waiting a few years before “throwing our caps over the cyclotron” and emphasizes the need for currently planned trials of fast neutron therapy versus megavoltage therapy by installing a neutron machine in medical centers which can compete with good penetrating beams and geometry, as are generated by state-of-the-art, high energy linear accelerators. Although neutron therapy has been shown to be very effective in eradicating gross salivary gland tumors, the excellent results achieved by a mixed photon and electron schedule; in the postoperative setting where there is minimum residuum and the major portion of the tumor has been excised, is reported by McNaney et al. A local-regional control rate of 87% was achieved and the authors argue for facial nerve preservation, if it is not grossly involved. The isodose curves for 20 MV photons and 18 MV electrons provide excellent coverage of the tumor bed with a minimum complication rate. Also in this issue, is a state-of-the-art report by Tadros et al on the ability of total skin electron irradiation to control mycoses fungoides. Despite delivering doses of 3000 cGy with 3 MV electrons and a 5-year actuarial survival of 66.7%, only a disease-free survival of 21.4% was achieved. As anticipated, an early stage patient with Tt Tz Na disease has frequent, complete responses and better relapse-free survival than advanced states. Although patterns of failure were predominantly in sites of previous involvement, extracutaneous dissemination was a frequent cause of death. Attention to radiation technique is essential, with need to provide dose homogeneity and particular attention to shielding. Although the radiation dose was an important determinant in outcome; higher doses, according to the authors, were not possible without increasing the morbidity of the acute skin reaction. Although tumor masses due to incomplete beam penetration may be an explanation for common relapse in skin, the frequency of dissemination of circulating T cells argues for new approaches with systemic agents, such as the addition of chemotherapy as adjuvants to improve results, particularly in advanced stages of this disease where total skin electron irradiation by itself is of limited effectiveness. A variety of other subjects are of interest and include late effects of radiation and chemotherapy. The increase in bone marrow activity in protected, unirradiated sites after extended field therapy has been documented by Parmeatier et al. This compensatory mechanism allows for return of peripheral blood counts shortly after treatment and persists for years. The liver complications reported by Haddad et al add adriamycin and CCNU to active agents that enhance untoward liver effects and the need for dose reduction to the 10 Gy level to be within tolerance. Elevations of liver enzymes, veno-occlusive disease, hepatomegaly and ascites have all been noted to occur, but the importance of biopsy confirmation is stressed.
1253
1254
Editor’s Note
In the report by Littman et al, dealing with soft tissue sarcomas of the head and neck in children, radiotherapy and combination chemotherapy proved successful for a 75% 5-year survival rate. Although various complications were encountered, few were so severe as not to recommend the current program of management. Their observation of the benefit of total cranial irradiation, where the base of the skull is involved, is strongly suggested by the extensive meningeal invasion that occurred when parameningeal CT changes were noted. Tef’ft, in his editorial, indicates the importance of maintaining quality of research at a single institution in clinical trials and how it reinforces the achievements and results of intergroup national trials. An important topic is the Oncology Intelligence offering, “The Flexure Dose” by Tucker and Thames, which is defined “as the largest fractional dose for which further fractionation produces no significant change in total dose required to reach a specific effect level.” The flexure dose is defined as a multiple of CX//~ of the parameters in the linear quadratic model of cell survival and estimates are offered for a large variety of normal and neoplastic tissues. The dissociation between acute and late radiation effects, often hyperfractionation, can be explained on the basis of a flexure dose for late reacting tissues that is smaller than that for tumors and acutely responding tissues. PHILIP RUBIN, M.D. Editor-in-Chief