Oropharynx carcinoma: irradiation alone versus induction chemotherapy plus irradiation--5 year results.

Induction chemotherapy (CT) has demonstrated overall response rates of 80% for oropharynx carcinomas, but no overall survival benefit has been reported. In order to determine the value of induction CT for such patients, we conducted a retrospective study: 121 patients were treated with CT and radiotherapy (RT) (Group 1). This group was compared with a historical group of 84 patients treated by RT alone (Group 2). The CT used was Cisplatinum associated with Bleomycin and Vincristin or Vindesin and with 5 Fluoro-uracil. An objective response to CT was observed for 41% of patients. The 5 year actuarial survival rate was 19% for Group 1 and 24% for Group 2. Patterns of failure were identical in the two groups. The only difference observed was for patients with N3 nodes (26% of 5 year survival rate in Group 1 versus 9% in Group 2) (p = 0.05). The results did not depend on the histological differentiation, the tumour site or the type of CT. We conclude that this retrospective study failed to demonstrate an advantage for induction CT in oropharynx carcinoma except for patients with N3 nodes.     

Techniques for management of vulvar cancer by irradiation alone

Vulvar cancer has traditionally been managed surgically, rather than by means of irradiation, because of the poor tolerance of the vulvar skin and mucous membranes to X-ray treatment. The use of moderate dose (4,000 rad) external-beam radiotherapy (EXRT) combined with two interstitial 192iridium endocurietherapy (ECT) applications of 2,500 rad to 3,000 rad allows delivery of an adequate tumoricidal dose (9,000 rad to 10,000 rad total dose) without producing radiation vulvitis. Irradiation is an effective alternate means of treatment in elderly patients who are medically unfit for radical vulvectomy and lymphadenectomy. It also provides an alternative to surgery for those patients who desire preservation of the genitourinary anatomy.     

Combined treatment with X-ray irradiation and 5-aminolevulinic acid elicits better transcriptomic response of cell cycle-related factors than X-ray irradiation alone

Purpose: 5-Aminolevulinic acid (ALA) is a precursor of the photosensitizer protoporphyrin (PpIX) used in photodynamic therapy. In our previous work, PpIX enhanced the generation of reactive oxygen species by X-ray irradiation. In this study, we evaluated the potential of ALA as an endogenous sensitizer to X-ray irradiation.

Methodology: Tumor-bearing C57BL/6J mice implanted with B16-BL6 melanoma cells were subsequently treated with irradiation (3?Gy/day for 10 days; total, 30?Gy) plus local administration of 50?mg/kg ALA 24?hours prior to each irradiation (ALA-XT). Tumor-bearing mice without treatment (NT), those treated with ALA only (ALAT), and those treated with X-ray irradiation only (XT) were used as controls.

Results: ALA potentiated tumor suppression by X-ray irradiation. In microarray analyses using tumor tissue collected after 10 sessions of fractional irradiation, functional analysis revealed that the majority of dysregulated genes in the XT and ALA-XT groups were related to cell-cycle arrest. Finally, the XT and ALA-XT groups differed in the strength of expression, but not in the pattern of expression.

Conclusions: mRNA analysis revealed that the combined use of ALA and X-ray irradiation sensitized tumors to X-ray treatment. Furthermore, the present results were consistent with ALA’s tumor suppressive effects in vivo.     

Comparative evaluation of combined irradiation and hyperthermia versus irradiation alone

Controvesy remains as to the treatment schedule producing better results in combined hyperthermia and X-ray therapy. Our experience concerning combined therapy of the solid tumour Walker carcinoma is reported. Male Wistar rats were submitted to treatment on the ninth day after transplantation of the tumour. Two groups of rats received either a therapeutic X-ray dose of 800 cGy by a 6-MeV linear accelerator (Mevatron, Siemens) or treatment by 432 MHz of microwaves with continuous control of tumour tissue temperature to 44 ± 1 °C for 45 min. Another group of rats was submitted to a combined treatment, with X-ray therapy preceding hyperthermia by 24 h. The last group of animals constituted the control rats. Greater tumour regression and longer survival times were obtained with the combined treatment. The gain factor for survival time was equal to 1.85 after combined treatment compared with 1.30 after X-ray therapy and 1.05 after hyperthermia. In conclusion, the results suggest that in the above schedule of combined treatment, hyperthermia applied to a solid tumour 24 h after a single dose of X-rays enhances the beneficial effect of therapy. Correspondence to: C. Sawas-Dimopoulou     

Alterations in water and electrolyte absorption in the rat colon following neutron irradiation: influence of neutron component and irradiation dose

PURPOSE: To study the absorptive function of rat colon following whole-body exposure to neutron irradiation, either to the same total dose with varying proportion of neutrons or to the same neutron proportion with an increasing irradiation dose. MATERIALS AND METHODS: Different proportions of neutron irradiation were produced from the reactor SILENE using a fissile solution of uranium nitrate (8, 47 and 87% neutron). Water and electrolyte fluxes were measured in the rat in vivo under anaesthesia by insertion into the descending colon of an agarose gel cylinder simulating the faeces. Functional studies were completed by histological analyses. In the first set of experiments, rats received 3.8 Gy with various neutron percentages and were studied from 1 to 14 days after exposure. In the second set of experiments, rats were exposed to increasing doses of irradiation (1-4Gy) with a high neutron percentage (87%n) and were studied at 4 days after exposure. RESULTS AND CONCLUSIONS: The absorptive capacity of rat colon was diminished by irradiation at 3-5 days, with a nadir at 4 days. The results demonstrate that an increase in the neutron proportion is associated with an amplification of the effects. Furthermore, a delay in the re-establishment of normal absorption was observed with the high neutron proportion (87%n). A dose-dependent reduction of water absorption by rat colon was also observed following neutron irradiation (87%n), with a 50% reduction at 3 Gy. Comparison of this dose-effect curve with the curve obtained following gamma (60)Co-irradiation indicates an RBE of 2.2 for absorptive colonic function in rat calculated at 4 days after exposure.     

Alterations in water and electrolyte absorption in the rat colon following neutron irradiation: influence of neutron component and irradiation dose

Purpose : To study the absorptive function of rat colon following whole-body exposure to neutron irradiation, either to the same total dose with varying proportion of neutrons or to the same neutron proportion with an increasing irradiation dose. Materials and methods : Different proportions of neutron irradiation were produced from the reactor SILENE using a fissile solution of uranium nitrate (8, 47 and 87% neutron). Water and electrolyte fluxes were measured in the rat in vivo under anaesthesia by insertion into the descending colon of an agarose gel cylinder simulating the faeces. Functional studies were completed by histological analyses. In the first set of experiments, rats received 3.8 Gy with various neutron percentages and were studied from 1 to 14 days after exposure. In the second set of experiments, rats were exposed to increasing doses of irradiation (1-4Gy) with a high neutron percentage (87%n) and were studied at 4 days after exposure. Results and conclusions : The absorptive capacity of rat colon was diminished by irradiation at 3-5 days, with a nadir at 4 days. The results demonstrate that an increase in the neutron proportion is associated with an amplification of the effects. Furthermore, a delay in the re-establishment of normal absorption was observed with the high neutron proportion (87%n). A dose-dependent reduction of water absorption by rat colon was also observed following neutron irradiation (87%n), with a 50% reduction at 3 Gy. Comparison of this dose-effect curve with the curve obtained following gamma 60 Co-irradiation indicates an RBE of 2.2 for absorptive colonic function in rat calculated at 4 days after exposure.     

Breast cancer with extensive intraductal component: treatment with immediate interstitial boost irradiation.

Extensive intraductal component (EIC) has been reported to have a prominent role in local recurrence after treatment of early-stage breast cancer with lumpectomy and irradiation. Pathologic specimens from 250 breasts (245 patients) treated between June 1982 and June 1990 with lumpectomy, immediate (boost) interstitial iridium-192 to 15-20 Gy, and external-beam irradiation to the entire breast to 45-50 Gy were reviewed. EIC was present in 61 breasts. At a median follow-up period of 58 months (range, 14-110 months), there were 10 recurrences in the 250 treated breasts. Of these 10, three were in patients from the group with EIC. The 10-year actuarial recurrence rates in breasts with and without EIC were 9.1% and 5.2%, respectively. The difference between the two rates was not significant. If an immediate boost with interstitial iridium is used in therapy, the influence of EIC on local failure is insignificant.     

Individualization of post-mastectomy radiotherapy and regional nodal irradiation based on treatment response after neoadjuvant chemotherapy for breast cancer

Purpose

To review the evidence regarding post-mastectomy radiotherapy (PMRT) and regional nodal irradiation (RNI) after neoadjuvant chemotherapy (NACT) for breast cancer, with a special focus on individualization of adjuvant radiotherapy based on treatment response.

Methods

A systematic literature search using the PubMed/Medline database was performed. We included prospective and retrospective reports with a minimum of 10 patients that had been published since 1^st January 2000, and provided clinical outcome data analyzed by treatment response and radiotherapy.

Results

Out of 763 articles identified via PubMed/Medline and hand search, 68 full text-articles were assessed for eligibility after screening of title and abstract. 13 studies were included in the systematic review, 9 for PMRT and 5 for RNI. All included studies were retrospective reports.

Conclusions

There is a considerable lack of evidence regarding the role of adjuvant radiotherapy and its individualization based on treatment response after NACT. Results of prospective randomized trials such as NSABP B?51/RTOG 1304 and Alliance A11202 are eagerly awaited.

     

Esophageal complications in the treatment of oat cell carcinoma with combined irradiation and chemotherapy.

A case of esophageal stenosis was noted in a patient treated with a combination of irradiation and chemotherapy for oat cell carcinoma. Review of the entire series of 22 patients revealed an unusually high rate (8/22) of esophagitis. These complications are discussed in relation to timing radiation dose and multidrug chemotherapy     

Acid phosphatase response in murine rhabdomyosarcoma for various tumour volumes and after different doses of neutron irradiation, alone or combined with exogenous ATP

Acid phosphatase activity measured in a methylocholanthrene-induced murine rhabdomyosarcoma showed a monotonically increasing relation between enzyme activity and tumour volume. This could be related to the lytic activity of the enzyme in large tumours which become more hypoxic and necrotic, and hence enhance degradation and turnover of damaged tumour cells. The tumours were also subjected to irradiation using doses of 2.0, 3.8 and 6.0 Gy from a neutron therapy facility p(66MeV)/Be. The correlation between different doses and response of acid phosphatase activity could reflect the relation of magnitude of damage from metabolic disturbances, with dose. Furthermore exogenous ATP was shown to provide radioprotective action against neutron irradiation in two different experiments. The ATP reduced the activity of this lytic enzyme in irradiated tumours and also decreased tumour growth delay. This radioprotective role of exogenous ATP in a murine tumour could be related to physiological regulatory processes during defence mechanisms to maintain self-organisation in response to the radiation damage.     

Mammographic findings after breast cancer treatment with local excision and definitive irradiation

Following local excision and definitive irradiation of 163 breast cancers in 160 women, alterations in mammographic patterns were observed for up to 7 years. Skin thickening was observed in 96% of mammograms obtained within 1 year of completing therapy and was most pronounced in women treated with iridium implant, chemotherapy, or axillary dissection. In 76% of mammograms, alterations in the parenchymal pattern, including coarsening of stroma and increased breast density, were seen at 1 year. Neither skin nor parenchymal changes progressed after 1 year. Within 3 years of treatment the parenchymal density, which usually regressed, did not change in all patients. At 3 years skin thickness and the parenchymal pattern had returned to normal in less than 50% of the breasts of these women. Scars developed in approximately one-quarter of women. They were present on the initial post-treatment mammogram and remained unchanged on serial studies. Coarse, benign calcifications also developed in the breasts of about one-quarter of women. Microcalcifications developed in 11 breasts; biopsy specimens of six were benign. Benign microcalcifications may be related to therapy.