Therapeutic options for breast cancer treatment in patients previously irradiated for Hodgkin's disease: radical mastectomy or conservative surgery followed by reirradiation?

Patients undergoing radiotherapy for the treatment of Hodgkin' disease (HD) occurred at young age present a higher risk to develop second cancer compared to general population. Among the possible second tumours, breast cancer is the most frequent and the age at presentation is younger than the "classic" form. Patients at risk for second cancer undergo a strict follow-up permitting often to diagnose breast cancer at early stages (I-II).The aim of this work is to review the various therapeutic options for the treatment of breast cancer in patients previously irradiated for HD, with particular attention to the possibility of reirradiation of mammary tissue thanks to the new radiotherapy techniques developed in the last years.

Elderly and poor prognosis patients with high grade glioma: hypofractionated radiotherapy.

AIM: To evaluate efficacy of short-course radiotherapy in elderly and/or poor performance status patients with high grade glioma. MATERIALS AND METHODS: Twenty-one patients with high grade astrocytoma were selected in our Institute to receive hypofractionated radiotherapy. We considered two radiotherapy treatment arms: in arm I there were 22 patients treated with 60 Gy in 30 fractions at 5 fractions per week; in arm 2 there were 21 patients who received hypofractionated radiotherapy course of 30 Gy in 10 fractions at 5 fractions per week. RESULTS: In arm1 the median survival time was 8.2 months and the 1 year overall survival was 36%; in arm 2 the estimated median survival was 6.2 months and the 1 year overall survival was 23%. Treatment was without acute toxicity. CONCLUSIONS: In our experience, hypofractionated radiotherapy seems to be a reasonable treatment option for poor prognosis patients with high grade astrocytoma. It is well tolerated and can reduce the overall treatment time without negative effects on survival compared with conventional fractionation.

Local recurrence in breast cancer after conservative surgery: timing of radiotherapy and sequencing of chemotherapy.

BACKGROUND: A randomized trial was conducted to determine (a) the role of radiotherapy and chemotherapy on local control and (b) to determine the timing of radiotherapy for early-stage breast cancer. MATERIALS AND METHODS: Five hundred and ninety patients were treated with both conservative surgery and radiotherapy (group A). The average time interval between surgery and radiation was 90 days for 452 patients and over 90 days for 138 patients. One hundred and ninety-four patients underwent adjuvant therapy based on CMF regimens (group B). RESULTS: Among 396 patients of group A, 8.1% had local failure; we observed 7.2% local recurrences in 363 patients who received therapy before 90 days and 18.2% in patients who received therapy after 90 days. Among patients of group B, 7.7% had local failure; for patients who underwent radiotherapy before 90 days, the local recurrence rate was 6.6%, compared with 12.3% for patients who underwent therapy more than 90 days after surgery. CONCLUSION: In patients who are eligible to receive chemotherapy, it is possible to administer radiotherapy after systemic treatment, while in patients who have to be treated with radiotherapy more then 90 days after breast surgery, chemotherapy can reduce the local failure rate.

Current radiotherapic procedures and preservation of salivary function in patients with head and neck cancer.

Head and neck tumours have poor prognosis: with surgery and radiotherapy, local control is achieved but is associated with damage to speech and swallowing function. Conventional 2-D radiotherapy is based on one fraction of 1.8-2.0 Gy per day; increasing the number of fractions, a higher dose can be administered, with an increase in local control. Today, conventional treatment can be replaced by new techniques: with 3-D Conformal Radiotherapy, higher doses of radiation can be delivered to cancer cells while reducing the amount of radiation received by surrounding healthy tissues: Intensity Modulated Radiation Therapy permits an irregular dose distribution that conforms exactly to the volume of the target, increasing local tumour control and survival and decreasing radiation-induced side-effects.

Radiation therapy for oncological emergencies.

AIMS AND BACKGROUND: Radiation therapy holds a fundamental role in oncological emergencies such as superior vena cava syndrome, spinal cord compression and endocranial hypertension. The purpose of our study was, by comparing schedules of treatment, to confirm the efficacy of hypofractionated radiation therapy. METHODS: From January 1994 to December 1998, 43 patients with superior vena cava syndrome, 37 patients with metastatic spinal cord compression and 108 patients with endocranial hypertension secondary to metastasis were treated at our institution. In the group of patients with superior vena cava syndrome, radiotherapy schedules were: 4 Gy x 5 to a total dose of 20 Gy (23 patients) and 3 Gy x 10 to a total dose of 30 Gy (20 patients). In the group of patients with spinal cord compression, radiation schedules were: 3 Gy x 10 to a total dose of 30 Gy (15 patients); 4 Gy x 5 to a total dose of 20 Gy (12 patients); a single fraction of 8 Gy in 10 cases, repeated after 1 week in 7 responder cases to a total dose of 16 Gy. 5 out of 37 patients were underwent to laminectomy plus stabilization of the spine and post-operative radiotherapy. In the group of patients with endocranial hypertension, radiotherapy schedules were: 6 Gy x 2 to a total dose of 12 Gy (53 patients), repeated after 4 weeks in 34 responder patients and 3 Gy x 10 to a total dose of 30 Gy (55 patients). RESULTS: The patients with superior vena cava syndrome, revaluated after 4 weeks at the end of treatment, obtained a partial remission of symptomatology in 73.9% with 20 Gy and in 75% with 30 Gy. The patients with spinal cord compression obtained symptomatic relief in 73.3% with 30 Gy, in 66.6% with 20 Gy and in 70% of cases treated with 8 Gy. The patients with endocranial hypertension obtained symptomatic relief in 64.1% with 12 Gy and in 63.3% with 30 Gy. CONCLUSION: Histology, pretreatment and performance status were important prognostic factors for the response to therapy. Our results demonstrated no significant difference among different schedules of radiotherapy and confirmed the importance of radiotherapy for oncological emergencies: it improves the quality of life and, in responding patients, is associated with a longer survival time.

[Exclusive radiotherapy in stage III esophageal cancer]. / Radioterapia esclusiva nel cancro dell'esofago stadio III.

BACKGROUND: The purpose of the report is to evaluate the role of radiotherapy in the treatment of stage III esophageal carcinoma and to analyze the influence of site, extension, grade of dysphagia and histology on local control and survival. METHODS: Twenty males and 6 females were submitted to external beam therapy with 4-6 MV X-rays and received 60-70 Gy in fractions of 180 cGY to 200 cGy per day, 5 days a week. Radiation therapy technique was two posterior oblique portals and a single anterior field at 100 cm SAD. After 4500 cGy portals were coned down, holding the spinal cord dose below 4500 cGy. RESULTS: Global response to therapy was 73.1%. Median survival was 11 months. The 2-year survival rate was 12.5% in patients with lesions smaller than 5 cm and 5.5% for those with lesions greater than 5 cm. Patients with grade 2 dysphagia had a median survival of 16 months, those with grade 1, 11 months and 2 patients with grade 0, 4 and 9 months. In all patients mild to moderate esophagitis was observed. Two patients developed esophagotracheal fistula. CONCLUSIONS: Exclusively radiotherapy cannot be considered the treatment of choice in III stage patients. Primary chemoradiotherapy may emerge as the treatment of choice for cancer of the esophagus.

Collaterals of recurrent laryngeal nerve fibres innervate the thymus: a fluorescent tracer and HRP investigation of efferent vagal neurons in the rat brainstem.

The origin and course of efferent vagal fibers, which innervate the rat thymus, were investigated by a fluorescent retrograde double labeling method, using Fast blue (FB) and Diamidino yellow dihydrochloride (DY) as tracers. In the same animal, one tracer was injected into the cranial portion of the right lobe of the thymus and the other dye was deposited around the cut end of the right recurrent laryngeal nerve. The neuronal population giving origin to the recurrent nerve was mapped by using retrograde labeling with HRP applied to the central stump of the nerve. The HRP retrograde axonal transport showed that most efferent vagal fibers of the recurrent nerve have their perikarya in the nucleus retroambigualis (NRA), nucleus ambiguus (NA), and to a lesser extent in the nucleus retrofacialis (NRF). In fluorescent retrograde double labeling of thymus and recurrent laryngeal nerve both single and double labeled cells were found. The cells labeled by the injections into the thymus were colocalized with the neurons labeled by the tracer deposited in the recurrent laryngeal nerve to the NRA, NA, and NRF. Moreover along the rostrocaudal extent of the NRF and NA double labeled cells were present, showing that some of the thymic efferents are collaterals of the recurrent nerve fibers. Our experiments shown that some thymic vagal fibres originate from neurons of nucleus dorsalis nervi vagi (NDV) as demonstrated both by HRP and FB injected thymuses. The possible role of these efferents in thymic function is briefly discussed.

Radiation therapy and chemotherapy in the treatment of head and neck extranodal non-Hodgkin's lymphoma in early stage with a high grade of malignancy.

BACKGROUND: Optimal management of patients with localized head and neck extranodal lymphoma remains controversial, both because of the lack of randomized studies and because of the heterogenous grouping of most reported series. MATERIALS AND METHODS: Patients treated at our institution between 1974 and 1993 for extranodal head and neck lymphoma were retrospectively analyzed and classified. The therapy and outcome of 92 patients classified as having an intermediate (42) and high (50) level of malignancy according to the Working formulation and in stage I (39) or II (53) of the Ann Arbor Staging System were considered. Fifty-three patients (57.6%) received chemotherapy alone, and 39 (42.4%) combined radiochemotherapy. RESULTS: The different treatment schedules allowed these patients to achieve global actuarial 5-year overall, event-free, and relapse-free survival rates of 81.2%, 78.1% and 89.3%, respectively. The patients that received combined modality treatment reported actuarial 10-year event-free and relapse-free survival rates of 65.3% and 90.7%, respectively, with a suggestion of decreased treatment-related morbidity compared to patients treated with chemotherapy. CONCLUSIONS: Our results underscore the important treatment role of combined radiochemotherapy for early stage intermediate and high grade lymphomas.

Fractionated total body irradiation in allogeneic bone marrow transplantation in leukemia patients: analysis of prognostic factors and results in 136 patients.

BACKGROUND AND PURPOSE: The results of a single-institution series of patients with chronic and acute leukemias are analyzed with regard to literature-reported predictor variables. MATERIALS AND METHODS: Between 1985 and 1994, 136 patients, 82 patients with chronic myeloid leukemia (CML) and 54 with acute leukemia (AL), received a uniform preparatory regimen of fractionated total body irradiation (TBI; 12 Gy in 3 days) plus different chemotherapy regimens before bone marrow transplantation. Eighty-six patients were considered to be in early phase of disease (CML in chronic phase or AL in first complete remission) and 50 in advanced phase (all those beyond first remission or first chronic phase). Ninety-five patients received unmanipulated allogeneic BM, and 41 T-lymphocyte-depleted BM. RESULTS: The 5-year overall survival (OS) and disease-free survival (DFS) of the whole series were 43% and 31%, and median survival was 43 and 10 months, respectively. A Cox proportional hazard model identified variables related to overall and disease-free survival. For OS, graft versus host disease (GVHD) was the first independent variable (P < 0.0001), followed by age (P < 0.001), T-depletion (P < 0.01), disease status (P < 0.05) and type of leukemia (P < 0.05). With regard to DFS, only T-depletion (P < 0.0001), disease status (P < 0.01) and GVHD (P < 0.01) resulted predictor factors. Early complications after BMT were reported in 59 patients, TBI-induced delayed toxicity in 9 patients, and 16 patients suffered late complications. CONCLUSIONS: Our results confirm the curability of early phase leukemias with standard fractionated TBI-induced Allogeneic bone marrow transplantation (ABMT). With an homogeneous fractionated TBI schedule as employed in our series, T-cell depletion negatively affected the outcome.

Multicentre experience with combined hyperthermia and radiation therapy in the treatment of superficially located non-Hodgkin's lymphomas.

The combination of Radiation Therapy (RT) and Hyperthermia (HT) has proved to be an effective treatment for a wide variety of superficially located recurrences of different tumors, particularly those arising in previously irradiated areas. Few studies on the use of HT in the management of lymphomatous diseases have so far obtained interesting results. Eight patients with Non Hodgkin Lymphomas (LNH) - 4 with cutaneous lymphomas and 4 with nodal recurrences after RT-Chemotherapy (CHT) treatment treated in three different Italian institutions with combined RT and HT are here reported. Rt dose ranged from 15 to 40 Gy with different fractionations, on the basis of previously received treatment. Hyperthermia was delivered using 432 or 915 MHz external microwave applicators, according to extension and depth of the lesions and available equipment. All patients tolerated well the HT treatment, and in all cases average intratumoral temperatures were >42 degrees, with 3 out of 10 treated sites achieving the goal of average temperatures >42.5%. One patient, with recurrent NHL, is disease-free after 24 months from completion of combined therapy. Our results seem to confirm previous experiences, suggesting a role of HT/RT not only for palliative purposes in cutaneous lymphomas, but also as an adjunct to radiotherapy alone in selected patients with superficially located recurrences.

[Radiotherapy of bone tumors. Analysis of a historic series and review of the literature]. / La radioterapia dei tumori ossei. Analisi di una casistica storica e revisione della letteratura.

The authors report a series of patients with osteosarcoma or Ewing's sarcoma irradiated 1968-1988 at the Institute of Radiology of "La Sapienza" University, Rome. Twelve of 17 osteosarcoma patients (71%) died and 5 are alive, with a median survival of 13 months. Seven of 12 Ewing's sarcoma patients (58%) died and 5 are alive (42%), with a median survival of 67 months. These results are similar to those of most contemporary series in the literature; the long follow-up of our series allowed us to calculate actuarial survival rates at 5, 10 and 15 years of 41%, 34% and 17%, respectively, in osteosarcoma patients and 75%, 45% and 34% for those with Ewing's sarcoma. The review of the literature on the management of bone tumors high-lights the importance of new developments and technologies to improve the life expectancy of these patients. The authors discuss the role of modern imaging techniques in defining tumor margins and predicting treatment-induced tumor regression and the research into new therapeutic approaches. Multimodality combinations and new schedules appear promising tools to improve prognosis and to reduce side-effects, thus stressing the need of combined efforts of surgeons, radiotherapists and chemotherapists. State-of-the-art radiotherapy can further increase local control with higher total doses to the lesion and selectively sparing adjacent normal tissues, thanks to 3D treatment planning of hadron beam equipment.

[The esthetic results in patients undergoing postoperative radiotherapy in breast carcinoma]. / Risultati estetici nelle pazienti sottoposte a radioterapia postoperatoria nel carcinoma mammario.

INTRODUCTION: Early stage breast cancer (pT-T2, N0, N+, M0) is generally treated with conservative surgery followed by radiation therapy, which procedures yield similar results to radical surgery. We studied the effects of irradiation on residual breast parenchyma in patients submitted to quadrantectomy and complementary irradiation. MATERIAL AND METHODS: 331 patients (Stage T1, T2, N0, M0) submitted to quadrantectomy and axillary dissection 1980-1993, were examined. The tumor was localized in external quadrants in 257 cases and in internal ones in 74 cases. Radiotherapy was given with 4-6 MV photon beams produced by a linear accelerator; the total dose to the breast was 50 Gy with a 10 Gy boost to tumor bed. All the patients were submitted to follow-up mammography at 6 months, one and two years after the end of radiotherapy. Parenchymal density was evaluated on an arbitrary scale from 0 to 3. We also considered the following other parameters: skin thickness, calcifications, cysts and possible signs of recurrence. RESULTS: Trabecular patterns were unchanged in 41 patients (grade 0) and slightly changed in 67 (grade 1); 135 patients had grade 2 and 90 grade 3 changes. 254 patients had skin thickening. All the changes disappeared at 2-3 years' follow-up. The patients with bigger breasts had poorer cosmetic results. CONCLUSIONS: It is very important to assess irradiation-induced tissue changes to detect any early recurrence of breast carcinoma. All radiation-induced changes decrease over time, which confirms the good tolerance and the good cosmetic results of complementary irradiation for breast cancer

Hodgkin's disease stage I and II with exclusive subdiaphragmatic presentation. The experience of the Departments of Radiation Oncology and Hematology, University "La Sapienza" of Rome.

During the period 1978 to 1994, 1054 patients with Hodgkins's disease were evaluated and treated at the Departments of Radiation Oncology and Hematology, University "La Sapienza", Rome. A total of 549 patients presented with clinical or pathological stage I and II; 37 of these had Hodgkin's disease below the diaphragm (BDHD), and 512 above the diaphragm (ADHD). A comparison of patients with BDHD versus those with ADHD showed that the first group had a higher male to female ratio. A comparison of cases with stage II BDHD versus those with stage II ADHD showed that patients with BDHD were older (48 years vs 28 years), had different histologic features and a higher incidence of systematic symptoms (67% vs 33%). Stage II BDHD patients had a worse prognosis; in fact, there were significant differences in the overall survival and relapse-free-survival rates for cases with stage II BDHD versus those with stage II ADHD (overall survival, 46% vs 80%, P<0.001; relapse-free survival, 44% vs 69%, P<0.005). Stage was found to be the most important prognostic factor for BDHD cases without systematic symptoms treated with radiation therapy alone. The type of infradiaphragmatic presentation (intra-abdominal vs peripheral disease) did not influence outcome, probably due to the more aggressive therapy received by the intra-abdominal group. Treatment recommendations for BDHD cases should be tailored to the stage and the presence or absence of intra-abdominal localization. For patients with stage IA extended fields, irradiation (inverted Y) is sufficient. However, combined modality therapy should be the treatment of choice for stage II cases, particularly in the presence of intra-abdominal disease. Patients with systematic symptoms also require combined modalities.

Local hyperthermia and radiation therapy in the treatment of superficially located lymphomas and recurrent Hodgkin's disease.

The combination of radiation therapy CRT) and hyperthermia (HT) has proved to be an effective treatment of a wide variety of superficially located recurrences of different tumors, particularly those arising in previously irradiated areas. Some studies have been reported with the use of this combined approach in the management of cutaneous lymphomas or recurrent previously irradiated sites of Hodgkin's disease (HD). We report a small series of five patients with six located sites of recurrent HD, and four patients with six superficially located sites of non Hodgkin's lymphomas (NHL), all of them being treated with combined HT and RT at our institution. Local control was obtained in each of combined treatment fields, and all patients are alive after a median follow-up of 24 months. All the patients tolerated the HT treatments well, and in all cases average intratumoral temperatures were >42 degrees C, with 8 out of 12 sites achieving the goal of average temperatures >42.5 degrees C. Two patients, one with recurrent HD and one with NHL, are free of disease after 20 and 21 months from the end of combined therapy. Our results thus seem to confirm previous experiences, suggesting a role of HT/RT not only for palliative purposes in cutaneous lymphomas, but also in the management of selected, heavily pretreated patients with superficially located recurrences of HD.

Radiotherapy for T1 carcinoma of the glottis.

AIMS AND BACKGROUND: The management of patients with T1 carcinoma of the glottic larynx is controversial, because surgery and radiation therapy are reported to be effective treatments. Several studies have shown radiotherapy to be safe and effective, with a high percentage of voice preservation and minimal complications, but most Italian physicians prefer to surgically treat such patients. METHODS: From 1980 to 1990, 36 patients with stage I squamous cell glottic carcinoma were treated with radiotherapy alone at the institute of Radiology of University of Rome "La Sapienza". In all patients the irradiation fields were limited to the larynx, with field size ranging from 4 x 4 cm to 7 x 7 cm. Total tumor doses ranged between 51 and 70 Gy (median 60 Gy) with a mean number of 30 fractions of 2 to 3 Gy per fraction (3 or 5 fractions per week). RESULTS: After a median follow-up of 98 months, we observed an overall survival rate at 5 years of 91.4% and actuarial 10-year survival of 85.7%. Local control was achieved in 97.1% of cases, with an event-free survival of 94.2% at 5 and 10 years. No major complications like necrosis or persistent edema of the larynx were observed. Minor complications like dysphonia (8%) and dysphagia (5.5%) were temporary; laryngeal function was completely preserved at the end of therapy. Final voice quality ranged from good to excellent. CONCLUSIONS: Our series confirms that radiation therapy has a major role in the management of early glottic cancer, with results comparable to surgical approaches and with better voice preservation.

Head and neck extranodal non-hodgkin-lymphoma - radiation-therapy and chemotherapy.

One hundred and seventy-five patients with extranodal non-Hodgkin lymphoma (NHL) treated between 1974 and 1993 in the Institute of Radiology and in the Department of Haematology of 'La Sapienza' University of Rome, have been examined. The sites involved were: Waldeyer's ring 96 patients (tonsils 84, nasopharinx 12), parotid 20, orbit 16, oral cavity 16, paranasal sinus 7, mandible 7, nasal fossal 3, minor salivary glands 3, larynx 3, conjunctive 2, lacrymal glands 1, thyroid 1. One hundred and forty-three patients had high and medium grade unfavourable histology; 68 patients were in stage I, 67 in II, 23 in III and 17 in IV. Fifteen patients were treated with radiotherapy alone and 86% obtained complete remission (CR). Chemotherapy alone was used in 90 cases and 87% C.R, was achieved; when chemotherapy in association with radiotherapy was used in 70 cases 85% obtained CR. The actuarial survival rate was 79% and recurrence-free survival in those patients who achieved complete remission 87%. Surviving and relapse-free patients were analysed in relation to main prognostic factors and therapy, and patterns of recurrence are reported. From the analysis of these cases we can learn how systemic therapy combined with the general conditions of patients and histology can control the disease. A minor relapse incidence with pharmacological therapy combined with a radiotherapic loco-regional treatment was also ascertained.

Palliative radiotherapy for brain metastases.

Several studies have confirmed that results of different hypofractionated radiotherapy schedules for palliative purpose are similar to those of conventional higher doses. From 1992 to 1993, 56 consecutive patients with brain metastases were irradiated at our Institution. Three different schedules were used ranging between 18 and 40 Gy. Overall survival, clinical and radiological responses were evaluated with regard to schedules and prognostic characteristics of patient population. There were no significant differences between the treatments, even though patients with shorter estimated life expectancy were more likely to be irradiated with more hypofractionated radiotherapy. Short, cost effective treatments appear to be the best therapeutic option both for institution and patients in most palliative cases.

[Results of radiotherapy in patients with bladder carcinoma]. / Risultati del trattamento radioterapico nei pazienti con carcinoma vescicale.

The authors analyse the results of treatment with radiotherapy with therapeutic doses and traditional fractionation scheme 60 patients affected by bladder cancer, from 1980 through 1991, at the Institute of Radiology of the University "La Sapienza" in Rome. We evaluated the association of radiotherapy (RT) with trans-urethral resection and biopsy (TURB) and the association of RT with cystectomy (total or partial), both in T1-T2 and T3-T4 bladder stages. The mean follow-up was 85 months (from 24 months to 11 years). The survival at 5 years after completing the treatment was 33.3%; the survival of stages T1-T2 was of 40% at 5 years while that of stages T3-T4 was of 28.5%. Our study shows that the association of radiotherapy and TURB for T1 or T2 bladder cancer is an alternative to mutilating surgery like total or partial cystectomy; in this group, indeed, we showed a survival of 54.5% at 5 years as compared to the 28.5% of the group treated with cystectomy + RT. For T3 and T4 bladder cancer we had better results with surgery (total or partial cystectomy) and RT: in these patients the survival at 5 years was of 31%, while the group treated with TURB + RT showed a survival of 19%.

[Radiotherapy in the treatment of tumors of the nasopharynx in advanced stage]. / Radioterapia nel trattamento dei tumori della rinofaringe in stadio avanzato.

This series consists of 25 patients affected with nasopharyngeal carcinoma in an advanced stage (T3-T4) treated at the Radiation Oncology department of the Institute of Radiology, University "La Sapienza", Rome, from 1978 through 1988. The patients were irradiated with X-rays produced by a LinAc with 4 MeV energy, for a total dose of 60/75 Gy on tumor and 50/60 Gy on nodes. In 7 cases radiation therapy was combined with chemotherapy. Actuarial survival at 60 months was 47%; patients with T3 cancer treated with a total tumor dose over 65 Gy showed a significant statistical increase of survival. Adjuvant chemotherapy did not produce statistically significant increase of survival. Radiation therapy was the treatment of choice in nasopharyngeal carcinoma in an advanced stage, whereas the role of chemotherapy remains questionable, even though a bad prognosis requires aggressive and combined treatment.