The ALERT model of care for the assessment and personalized management of patients with lymphoedema.

BACKGROUND: This study documents the development and evaluation of a comprehensive multidisciplinary model for the assessment and personalized care of patients with lymphoedema. METHODS: The Australian Lymphoedema Education Research and Treatment (ALERT) programme originated as an advanced clinic for patients considering surgery for lymphoedema. The programme commenced liposuction surgery in May 2012 and then introduced lymph node transfer in 2013 and lymphovenous anastomosis (LVA) in 2016. An outpatient conservative treatment clinic was established in 2016. ALERT commenced investigations with indocyanine green (ICG) lymphography in late 2015, leading to the creation of a diagnostic assessment clinic offering ICG in 2017. RESULTS: Since 2012, 1200 new patients have been referred to ALERT for assessment of lymphoedema for a total of 5043 episodes of care. The introduction of ICG lymphography in 2015 initially allowed better screening for LVA, but is now used not only to guide surgical options, but also as a diagnostic tool and to guide manual lymphatic drainage massage. The total number of new patients who attended the surgical assessment clinic to December 2018 was 477, with 162 patients (34·0 per cent) undergoing surgery. CONCLUSION: The ALERT programme has developed a multidisciplinary model of care for personalized lymphoedema treatment options based on clinical, imaging and ICG lymphography. Patients are selected for surgery based on several individual factors.

ANTECEDENTES: Este estudio presenta el desarrollo y valoración de un modelo multidisciplinario integral para la evaluación y atención personalizada de pacientes con linfedema. MÉTODOS: El programa australiano de educación en investigación y tratamiento del linfedema (Australian Lymphoedema Education Research and Treatment, ALERT) se originó como un centro clínico avanzado para pacientes que consideran la cirugía como tratamiento para el linfedema. El programa se inició en mayo del 2012 con la cirugía de liposucción, introduciendo la cirugía de transferencia ganglionar (lymph node transfer, LNT) en 2013 y la anastomosis linfovenosa (lymphovenous anastomosis, LVA) en 2016. En 2016 se estableció una clínica de tratamiento conservador ambulatorio. ALERT comenzó las investigaciones con la linfografía con verde de indocianina (indocyanine green, ICG) a fines del 2015, lo que se siguió de la creación de una clínica de evaluación diagnóstica que ofrece ICG en 2017. RESULTADOS: Desde el 2012, 1.200 pacientes nuevos han sido referidos a ALERT para la evaluación de un linfedema, con un total de 5.043 episodios atendidos. La introducción inicialmente de linfografía con ICG en 2015 permitió un mejor cribaje para LVA, pero actualmente se utiliza no solo como guía de las opciones quirúrgicas, sino también como herramienta diagnóstica y como guía del masaje de drenaje linfático manual (manual lymphatic drainage, MLD). El número total de pacientes nuevos atendidos en la clínica de evaluación quirúrgica hasta diciembre de 2018 fue de 477, con 122 pacientes (34%) tratados quirúrgicamente. El modelo tal como se ha descrito, ha atraído a pacientes de toda Australia y Nueva Zelanda. CONCLUSIÓN: El programa ALERT ha desarrollado un modelo multidisciplinario de atención para las opciones de tratamiento personalizado del linfedema basado en la evaluación clínica, por imagen (MRI y LSG) y linfografía con ICG. Los pacientes se seleccionan cuidadosamente para el tratamiento quirúrgico en función de varios factores relacionados con el paciente, el tumor, los linfáticos y las opciones terapéuticas, y se someten a una evaluación detallada después de cualquier procedimiento.

Breast cancer survival and stage at diagnosis in Australia, Canada, Denmark, Norway, Sweden and the UK, 2000-2007: a population-based study.

BACKGROUND: We investigate whether differences in breast cancer survival in six high-income countries can be explained by differences in stage at diagnosis using routine data from population-based cancer registries. METHODS: We analysed the data on 257,362 women diagnosed with breast cancer during 2000-7 and registered in 13 population-based cancer registries in Australia, Canada, Denmark, Norway, Sweden and the UK. Flexible parametric hazard models were used to estimate net survival and the excess hazard of dying from breast cancer up to 3 years after diagnosis. RESULTS: Age-standardised 3-year net survival was 87-89% in the UK and Denmark, and 91-94% in the other four countries. Stage at diagnosis was relatively advanced in Denmark: only 30% of women had Tumour, Nodes, Metastasis (TNM) stage I disease, compared with 42-45% elsewhere. Women in the UK had low survival for TNM stage III-IV disease compared with other countries. CONCLUSION: International differences in breast cancer survival are partly explained by differences in stage at diagnosis, and partly by differences in stage-specific survival. Low overall survival arises if the stage distribution is adverse (e.g. Denmark) but stage-specific survival is normal; or if the stage distribution is typical but stage-specific survival is low (e.g. UK). International differences in staging diagnostics and stage-specific cancer therapies should be investigated.

Association between 25-hydroxyvitamin D concentration and breast cancer risk in an Australian population: an observational case-control study.

The objective of this study is to examine the association between vitamin D status and risk of breast cancer in an Australian population of women. The study design is observational case-control study, performed at Westmead Breast Cancer Institute, Westmead Hospital, Sydney, Australia. 214 women newly diagnosed with breast cancer were matched to 852 controls, and their blood samples were tested at the same laboratory between August 2008 and July 2010. Circulating 25-hydroxyvitamin D (25(OH)D) concentration, was defined as sufficient (≥75 nmol/L), insufficient (50-74 nmol/L), deficient (25-49 nmol/L) or severely deficient (<25 nmol/L). The difference in median 25(OH)D concentration between cases and controls was reported, and the Mann-Whitney U test was used to determine the significance of the difference. Odds ratios and 95 % confidence intervals for the risk of breast cancer were estimated by Cox regression. Median plasma 25(OH)D was significantly lower in cases versus controls overall (53.0 vs 62.0 nmol/L, P < 0.001) and during summer (53.0 vs 68.0 nmol/L, P < 0.001) and winter (54.5 vs 63.0 nmol/L, P < 0.001). Median 25(OH)D was also lower in cases when stratified by BMI (<30, ≥30) and age group (<50, ≥50 years) compared to matched controls, although the difference failed to reach statistical significance. In a Cox regression model, plasma 25(OH)D was inversely associated with the odds ratio of breast cancer. Compared to subjects with sufficient 25(OH)D concentration, the odds ratios of breast cancer were 2.3 (95 % CI 1.3-4.3), 2.5 (95 % CI 1.6-3.9) and 2.5 (95 % CI 1.6-3.8) for subjects categorised as severely deficient, deficient or insufficient vitamin D status, respectively. The results of this observational case-control study indicate that a 25(OH)D concentration below 75 nmol/L at diagnosis was associated with a significantly higher risk of breast cancer. These results support previous research which has shown that lower 25(OH)D concentrations are associated with increased risk of breast cancer.

Is lymphatic reconstitution possible after meshed skin grafting?

Restorative potential of lymph transport after skin graft has rarely been discussed. We report a case of lymphatic reconstitution across meshed, split-thickness skin graft performed for a patient with necrotizing fasciitis. The patient underwent extensive circumferential soft tissue debridement of the lower leg and resurfacing of the skin defect with meshed split-thickness skin graft. Indocyanine green fluorescence lymphography was performed 3 years after surgery and demonstrated that injected dye in the foot traveled across the skin graft and reached to the adjacent native skin in the proximal region. Our observation revealed that transferred split-thickness skin graft possessed some potential to allow for transport of lymph fluid possibly owing to the retention of lymphatic capillaries.

Combined chemotherapy and radiotherapy for patients with breast cancer and extensive nodal involvement.

PURPOSE: This retrospective review examines local control, freedom from distant failure, and survival for patients with nonmetastatic breast cancer with extensive nodal disease (> 10 nodes, 45 patients; or > or = 70% involved nodes, if < 10 nodes found, 19 patients). All patients received chemotherapy and radiotherapy following mastectomy. PATIENTS AND METHODS: Sixty-four patients were treated between January 1980 and December 1988 at Westmead Hospital, Westmead, NSW Australia. The median follow-up duration for surviving patients was 91.5 months (range, 56 to 121). The median age was 51 years, and the median number of positive nodes was 11. Four successive protocols evolved, each with three phases, as follows: induction chemotherapy (doxorubicin or mitoxantrone, plus cyclophosphamide; three cycles), radiotherapy (50 Gy in 25 fractions to chest wall and regional nodes), then chemotherapy (cyclophosphamide, methotrexate, and fluorouracil [CMF]) of progressively shorter duration. Radiotherapy and chemotherapy were concurrent in the fourth regimen. RESULTS: One patient (1.5%) developed local recurrence before distant relapse, and seven patients (11%) developed local and/or regional recurrence simultaneously or after distant relapse. The 5-year actuarial freedom from distant relapse and overall survival rates were 45% and 65%, respectively. Overall survival did not vary significantly by menopausal status, nodal subgroup, or dose-intensity. There were no treatment-related deaths. CONCLUSION: Combined chemotherapy and radiotherapy in standard dosage is an acceptable approach following mastectomy for patients with extensive nodal involvement at high risk for local recurrence and distant relapse. This approach should be considered standard best therapy for any randomized trials that examine high-dose chemotherapy or bone marrow transplantation for this subgroup of patients.

The presence of an extensive intraductal component following a limited excision correlates with prominent residual disease in the remainder of the breast.

Previous studies of patients with infiltrating ductal breast cancer treated with conservative surgery (ie, limited excision) and radiotherapy have indicated that the presence of an extensive intraductal component (EIC) in the excision specimen is highly associated with subsequent breast recurrence. The reason for this association is not clear, but possible explanations include the presence of more extensive disease in the breast or increased radiation resistance among tumors with an EIC (EIC+) compared with those without (EIC-) tumors. To investigate this association further, we related the presence or absence of an EIC in the primary tumors of 214 women who underwent mastectomy to the likelihood of finding additional foci of cancer in their mastectomy specimens using a correlated pathologic-radiologic mapping technique. Primary tumors that were EIC+ were significantly more likely to have carcinoma in the remainder of the breast than those which were EIC--(74% v 42%; P = .00001). This difference was primarily due to the presence of residual intraductal carcinoma. Seventy-one percent of EIC+ patients had residual intraductal carcinoma compared with 28% of EIC-patients (P less than .00001). In particular, 44% of EIC+ patients had "prominent" residual intraductal carcinoma compared with 3% of EIC-patients (P less than .00001). We conclude that patients whose tumors contain an EIC more frequently have a large subclinical tumor burden in the remainder of the breast compared with patients whose tumors do not contain an EIC. This observation may explain the association between EIC and subsequent breast recurrence when patients are treated with a limited excision before radiotherapy.

Can an Immediate 2-stage Breast Reconstruction Be Performed After Previous Conservative Surgery and Radiotherapy?

BACKGROUND: Prosthetic breast reconstruction is generally considered contraindicated after previous breast irradiation. As a result, patients undergoing a salvage mastectomy for recurrent breast cancer or "risk-reducing" mastectomies after previous conservative surgery and radiotherapy (CS + RT) are usually offered autologous breast reconstruction. However, not all such patients are suitable candidates for a major flap reconstruction. The purpose of this study is to review our results of immediate 2-stage prosthetic breast reconstruction after CS + RT. METHODS: A retrospective review was undertaken for 671 consecutive patients with prosthetic-only breast reconstruction performed by a single surgeon over a 12.5-year period. Twenty-two patients who qualified for the criteria were audited. Outcomes examined include complications, loss of tissue expander or implant, revisional surgery, and aesthetic result. RESULTS: Twenty-two patients underwent 33 mastectomies and immediate 2-stage breast reconstructions after previous CS + RT (15 for recurrent cancer and seven "risk-reduction") and 11 contralateral risk-reducing mastectomies. One patient died due to extensive metastatic disease. There was no reconstruction failure. The average breast implant size was 491.7 g (range 220 -685g). Seroma was the most common complication and occurred in 3 of 22 patients (13.6%) after stage 1 and 3 of 21 patients (14.3%) after stage 2 reconstruction. The revisional surgery rate was 28.6%. Aesthetic result was rated as excellent in 9.5%, good in 76.2%, and fair in 14.3%. CONCLUSIONS: For selected patients, immediate 2-stage prosthetic breast reconstruction can be performed successfully after a salvage mastectomy subsequent to a recurrence after CS + RT.

Recurrence in the breast following conservative surgery and radiation therapy for early-stage breast cancer.

This report summarizes the experience of the Joint Center for Radiation Therapy (JCRT) in treating patients with clinical stage I and II breast cancer with conservative surgery and radiation therapy. The study population consisted of 1396 patients treated between 1968 and 1985. All patients underwent a gross excision of the tumor and received breast irradiation (with or without nodal irradiation) including a "boost" to bring the primary tumor site to a total dose of at least 60 Gy. The method of treatment evolved over the study-time period. During the interval from 1968 to 1982, patients typically underwent a limited gross excision of the tumor without regard to the microscopic margins of resection. During the period 1983 to 1985, film-screen mammography, inking of specimen margins, and reexcisions for inevaluable or involved margins were more commonly performed. With a median follow-up of 80 months, the 5-year crude rate of failure in the breast (as the first site of failure) was 8% (106/1396) and the crude rate of regional nodal/distant failure (as the first site of failure) was 16% (228/1396). The time-course of failures in the breast was protracted, occurring at a fairly constant rate over the first 7 years after treatment, but still seen beyond that point. Most recurrences in the breast (75%) developed at or near the original tumor site. The most important risk factor for developing a breast recurrence was the presence of an extensive intraductal component in the tumor. The cosmetic results following treatment were excellent or good in the majority of patients (87%) and were most adversely affected by extensive surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

The efficacy of combined chemotherapy and radiotherapy in advanced non-metastatic breast cancer.

Thirty-five patients with locally advanced (inoperable) breast cancer have been treated based on a regimen of chemotherapy-radiotherapy-chemotherapy. At the completion of all treatment a complete remission rate of 86% was achieved with acceptable toxicity. At a median follow-up of 24 months (range 4-60), relapse at the site of bulk disease occurred in 17% (10% isolated loco-regional relapse) and relapse at distant sites in 34%. The median relapse-free survival was 36 months and the median survival has not yet been reached. Following initial promising results in terms of loco-regional disease control in this group of high-risk patients, the protocol was extended to include 34 patients defined as having locally extensive disease. All patients in this subgroup had undergone a modified radical mastectomy and were categorized as (a) patients in whom the pre-operative clinical findings merited (in our opinion) inclusion in the category of locally advanced (inoperable) disease, (b) patients in whom the primary was operable but in whom extensive involvement of axillary nodes was found (greater than 10 nodes positive or greater than or equal to 70% nodes positive if less than 10 nodes found) and (c) patients without the above characteristics with a primary tumor greater than 8 cm. At a median follow-up of 23 months (range 4-48), loco-regional recurrence occurred in one patient (3%) but distant relapse occurred in 21%. Relapse-free and overall survival was not significantly different to that found in patients with locally advanced disease who did not undergo mastectomy.

Malignant spinal cord compression: a prospective evaluation.

PURPOSE: To determine the influence of treatment on ambulancy, pain control and functional outcome of patients with Malignant Spinal Cord Compression. METHODS AND MATERIALS: One hundred and thirty-seven patients with Malignant Spinal Cord Compression presenting or referred to the Department of Radiation Oncology, Westmead Hospital between August 1, 1989 and August 1, 1990 were studied prospectively. Patients were treated with palliative radiation therapy alone, surgery followed by radiotherapy or surgery alone. Two patients were not treated. Post-treatment outcome was assessed in terms of ambulatory status, improvement in pain and functional independence using the Functional Independence Measure. RESULTS: Thirteen of 16 patients (81%) who were ambulant pre-treatment remained ambulant after treatment. Two of 16 patients (16.5%) who were non-ambulant pre-treatment became ambulant following treatment. Pain improved following treatment in 22 of 30 patients (73%). This benefit was seen equally for ambulant and non-ambulant patients. A high level of functional independence was maintained in patients who remained ambulant. CONCLUSION: We conclude that prompt treatment of patients with Malignant Spinal Cord Compression while still able to walk is effective in maintaining ambulancy and functional independence, and that treatment improves pain in most patients.

Locally advanced breast cancer: defining an optimum treatment regimen.

PURPOSE: This retrospective review examines response, local control and freedom from distant failure for patients with locally advanced breast cancer treated by chemotherapy and radiotherapy without routine surgery. METHODS AND MATERIALS: 67 patients were treated between January 1980 and December 1988 at Westmead Hospital, NSW, Australia. Median follow-up for surviving patients was 56 months. Four successive protocols evolved, each with three phases induction chemotherapy (adriamycin or novantrone, cyclophosphamide) (three cycles), radiotherapy then chemotherapy (cyclophosphamide, methotrexate, 5-fluorouracil) of progressively shorter duration. Radiotherapy and chemotherapy were concurrent in the fourth regimen. RESULTS: Clinical complete response (disappearance of all known disease) after chemotherapy, radiotherapy and additional chemotherapy was 18%, 55% and 79% respectively. Seven additional patients subsequently underwent mastectomy (N = 2), local excision (N = 1) or a radiation boost (N = 4) for a total complete response rate of 90%. Twenty one patients (31%) failed to achieve a complete response (N = 7) or recurred locally (N = 14). The crude 2-year rate of local recurrence was 50% for tumors > 10 cm (N = 10) and 14% for smaller tumors (n = 57) and was not influenced by protocol. Two-year actuarial freedom from distant failure was 67% at 2 years. CONCLUSION: Local control can be achieved for patients with locally advanced breast cancer with a primary tumor < 10 cm using chemotherapy and radiotherapy without routine mastectomy.

Breast conservation: long-term Australian data.

Long-term data on the management of early breast cancer in Australia by conservative surgery and radiation therapy is limited. To examine this issue we reviewed our experience of 131 patients with Stage I or II breast cancer treated between November 1979 and December 1985. Ninety patients had a T1 tumor and 41 a T2 tumor. The extent of surgery varied from a local excision (LE), a wide local excision, to a quadrantectomy or partial mastectomy. Sixty-two per cent of patients also had an axillary dissection. One hundred and nineteen patients were treated using 6Mev photons to the whole breast (Median dose; 50 Gy) +/- regional nodes followed by a single plane Iridium-192 boost to the primary tumor site (median dose; 30 Gy). Ten patients did not receive a boost and two elderly patients were treated with an implant only. The median follow-up of surviving patients was 83 months (range, 51-133 months). Six other patients were lost to follow-up at a median of 48 months (range, 4-62). The pattern of first relapse is: breast alone, 7.0%; breast + distant, 0.75%; breast + nodes, 0.75%; regional nodes only, 0.75%; and distant disease, 18%. The extent of surgery did not influence the probability of a recurrence in the primary tumor region. The time to a breast recurrence ranged from 12 to 127 months (median, 61 months). The 5-year actuarial rate of a breast recurrence was 4.5%. The 5-year freedom from distant relapse was 80%. The complications of treatment were acceptable. These included rib fracture (5%), symptomatic pneumonitis (4%), fat necrosis or fibrosis requiring surgery (4.5%), severe arm edema (4.5%). The treatment of the axilla by both surgery plus radiation therapy was associated with a moderate or severe arm edema rate of 29% compared to 8% for surgery alone and 6% for radiation therapy alone. Our long-term data indicate that conservative surgery plus radiation therapy is associated with low rates of breast cancer recurrence which are independent of the extent of surgical resection. Complications were acceptably low provided that the axilla was treated by surgery or radiation therapy but not by both modalities.

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

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

The predictors of distant relapse following conservative surgery and radiotherapy for early breast cancer are similar to those following mastectomy.

Although previous studies have indicated that the predictors of local recurrence following conservative surgery (CS) and radiotherapy (RT) are not the same as those following mastectomy, it remains unclear whether the predictors of distant relapse differ by local treatment modality. Clinical and pathologic features predictive of distant relapse for patients treated with mastectomy have been well established and include lymph node involvement, histologic grade, and peritumoral lymphatic vessel invasion (LVI). To study the influence of these and other factors on the rate of distant relapse in patients treated with CS and RT, we have identified a group of 438 patients treated between 1968 and 1981 who met the following criteria: primary tumor size less than or equal to 5 cm, excision of the primary tumor, infiltrating ductal carcinoma as the most aggressive histologic subtype, histology evaluable for the presence of an extensive intraductal component, and a dose to the primary site greater than or equal to 60 Gy. Estrogen receptor status was available in 58% of cases, 76% had an axillary dissection, and 23% were treated with adjuvant chemotherapy. With a median follow-up of 89 months, 107 patients (24%) developed a distant relapse. The 5-year actuarial freedom from distant relapse (FDR) was 80%. Stepdown Cox proportional hazards regression analysis identified several factors associated with a significantly (p less than 0.01) increased risk for distant relapse: positive lymph nodes, histologic grade, necrosis, and lymphatic vessel invasion. The magnitude of each effect was then examined with a lifetable calculation. Five-year freedom from distant relapse was 86% for the node-negative subgroup, 78% for patients with one to three positive nodes, and 45% for patients with four or more positive nodes. For histologic grades I, II, and III, 5-year freedom from distant relapse was 96%, 97%, and 75%, respectively. For necrosis scored as absent, scant, moderate, or marked, 5-year freedom from distant relapse was 90%, 78%, 77%, and 66%, respectively. For lymphatic vessel invasion scored as absent or present, 5-year freedom from distant relapse was 85% and 63%, respectively. We conclude that the clinico-pathologic predictors for distant relapse following conservative surgery and radiotherapy appear to be the same as those following mastectomy. This observation is consistent with the notion that distant relapse is caused by the presence of micrometastases at the time of initial patient sentation and is not greatly influenced by selection of local treatment.

Premenopausal breast cancer patients treated with conservative surgery, radiotherapy and adjuvant chemotherapy have a low risk of local failure.

The use of adjuvant chemotherapy in premenopausal breast cancer patients with positive nodes is now routine, but the optimal local treatment of these patients is uncertain. To determine the effect of adjuvant chemotherapy on the likelihood of local recurrence as the first site of failure in premenopausal patients treated with conservative surgery (CS) and radiotherapy (RT), we examined the outcome of 74 patients treated with CS, RT, and adjuvant chemotherapy and compared it to the outcome in 192 patients treated with CS and RT alone. Adjuvant chemotherapy consisted of four or more cycles of either a doxorubicin-containing regimen or cyclophosphamide, methotrexate, and 5-fluorouracil. All patients were less than 50 years old, had UICC-AJCC Stage I or II breast cancer treated between 1968 and 1981, had gross excision of the primary tumor, and had a total radiation dose to the primary tumor bed of greater than or equal to 6000 cGy. Factors predicting for local recurrence, such as extensive intraductal carcinoma and age less than 35, were equivalent in the two groups. Women treated with adjuvant chemotherapy had significantly worse T- and N-stages than women treated with conservative surgery and radiotherapy alone: 61% versus 36% had T2 tumors (p = 0.0003), 34% versus 6% had clinically positive nodes (p less than 0.0001), and 97% versus 4% had pathologically positive nodes (p less than 0.0001). Despite the poorer prognosis of patients treated with adjuvant chemotherapy, within 5 years of diagnosis, 4% of patients who received adjuvant chemotherapy had their initial relapse in the breast and 24% had initial failure elsewhere, compared with 15% local failure first and 14% failure elsewhere first for those treated without chemotherapy (p = 0.01). We conclude that premenopausal patients with positive nodes treated with combined modality therapy (conservative surgery, radiation therapy, and adjuvant chemotherapy) have a low risk of local recurrence as a first site of failure. These results suggest a possible interaction between radiation therapy and chemotherapy in their effects on local tumor control.

Cerebral hemisphere astrocytoma: treatment results.

Eighty two adult patients with histologically proven cerebral astrocytomas of grades I to IV received post-operative radiotherapy at Westmead Hospital between January 1980 and February 1985. The extent of surgery consisted of biopsy alone in 44%, subtotal tumour resection in 48%, and "complete" tumour removal in 8%. Seventy one patients completed a course of megavoltage irradiation, the majority having received a tumour dose of at least 60 Gy. Patients who underwent surgical resection (complete or incomplete) had a greater median survival (14 months) than those undergoing biopsy (8 months), but the difference was not statistically significant (p = 0.08). By grade, the difference reached statistical significance only for grade III tumours (p = 0.015). Patients with high grade tumours had a significantly lower survival than those patients with tumours of low grade. Median survival for patients with grades I and II, III and IV tumours was 42.0, 12.0 and 7.0 months, respectively. After adjustment for grade, various dosage levels (less than 60, 60 or greater than 60 Gy) did not significantly affect survival, although there was a trend towards improved median survival with higher doses in grade III tumours. Older patients (greater than 45 years) had a significantly lower median survival (25 months) than younger patients (8 months) (p less than 0.0001). When included in a multivariate analysis, the extent of surgery did not significantly influence survival, but increasing tumour grade and increasing age were significant adverse prognostic factors.

Fat necrosis of the breast following lumpectomy and radiation therapy for early breast cancer.

Between January 1980 and December 1985, 121 patients with early breast cancer were treated in the Department of Radiation Oncology at Westmead Hospital by external beam irradiation and an iridium wire boost following "lumpectomy". After a median follow-up of 26 months, 14 patients have developed recurrent masses in the treated breast. In four, recurrent carcinoma was strongly suspected and subsequently confirmed by fine needle aspiration biopsy, but in only two was a subsequent salvage mastectomy possible. The remaining 10 patients developed a nodule which was usually tender. With three exceptions, the nodule was at the primary tumour site and developed 4-43 months after treatment. In seven, tumour recurrence was suspected but not confirmed by biopsy and the other three were accepted as having post-treatment "radiation fibrosis". Excision biopsy was undertaken in eight of the 10 patients. Another patient underwent partial mastectomy for presumed local recurrence. The histological appearance in all cases was similar, with areas of fat necrosis and fibrosis with atypical stromal fibroblasts. Suture material was present microscopically in eight patients and was noted macroscopically (that is, by mammogram) in the one patient who did not undergo surgery. This complication is most likely caused by a combination of surgical and radiation factors. The difficulty in management is differentiation between tumour recurrence and a benign condition.

Early breast cancer: predictors of breast recurrence for patients treated with conservative surgery and radiation therapy.

The identification of factors associated with breast recurrence following conservative surgery (CS) and radiation therapy (RT) is of potential use in refining patient selection criteria and treatment technique. In an attempt to define such factors we examined the relationship between various clinical, pathologic and treatment characteristics and the likelihood of breast recurrence in 783 patients with clinical stage I or II breast cancer treated between July 1968 and December 1982. Treatment consisted of complete gross excision of the primary tumor and RT to a total dose of at least 60 Gy to the primary site. During this period, pre-treatment mammograms and detailed histologic assessment of the margins of resection were not routinely performed. Median follow-up for surviving patients was 80 months. Thirteen patients (1.6%) were lost to follow-up. Ninety-one patients (12%) have developed a breast recurrence, corresponding to 5- and 10-year actuarial rates of 10 and 18%, respectively. The major feature associated with breast recurrence was the presence of an "extensive intraductal component" (EIC+). An EIC+ tumor was seen in 28% of evaluable cases with infiltrating ductal carcinoma and accounted for 60% of breast recurrences. Forty-three of 166 patients (26%) with EIC+ tumors developed a breast recurrence compared with 29 of 418 patients (7%) without an EIC (EIC-) (p = 0.0001). The 5-year actuarial rates of breast relapse were 24 and 6%, respectively (p = 0.0001). Very young age (defined as 34 years of age or younger) was also a significant factor associated with the risk of breast recurrence. Very young patients comprised 8% of the patient population and accounted for 16% of breast recurrences. Fifteen of 61 very young patients (25%) developed a breast recurrence compared with 76 of 722 older patients (11%) (p = 0.001). The corresponding 5-year actuarial rates of breast recurrence were 21 and 9% (p = 0.005). None of the other clinical or pathological factors examined by univariate analysis were significantly correlated with recurrence in the breast. A multivariate model of site of first failure (polychotomous logistic regression) also showed that EIC+ tumors and very young age were the main factors associated with a high relative risk of breast recurrence. We conclude that EIC+ tumors and very young age are associated with a high risk of breast recurrence for patients treated with limited excision prior to RT.

Three-dimensional dose distribution of tangential breast irradiation: results of a multicentre phantom dosimetry study.

BACKGROUND AND PURPOSE: One aspect of good radiotherapeutic practice is to achieve dose homogeneity. Dose inhomogeneities occur with breast tangent irradiation, particularly in women with large breasts. MATERIALS AND METHODS: Ten Australian radiation oncology centres agreed to participate in this multicentre phantom dosimetry study. An Alderson radiation therapy anthropomorphic phantom with attachable breasts of two different cup sizes (B and DD) was used. The entire phantom was capable of having thermoluminescent dosimeters (TLD) material inserted at various locations. Nine TLD positions were distributed throughout the left breast phantom including the superior and inferior planes. The ten centres were asked to simulate, plan and treat (with a prescription of 100 cGy) the breast phantoms according to their standard practice. Point doses from resultant computer plans were calculated for each TLD position. Measured and calculated (planning computer) doses were compared. RESULTS: The dose planning predictability between departments did not appear to be significantly different for both the small and large breast phantoms. The median dose deviation (calculated dose minus measured dose) for all centres ranged from 2. 3 to 5.3 cGy on the central axis and from 2.1 to 7.5 cGy for the off-axis planes. The highest absolute dose was measured in the inferior plane of the large breast (128.7 cGy). The greatest dose inhomogeneity occurred in the small breast phantom volume (median range 93.2-105 cGy) compared with the large breast phantom volume (median range, 100.1-107.7 cGy). There was considerable variation in the use (or not) of wedges to obtain optimized dosimetry. No department used 3D compensators. CONCLUSION: The results highlight areas of potential improvement in the delivery of breast tangent radiotherapy. Despite reasonable dose predictability, the greatest dose deviation and highest measured doses occurred in the inferior aspects of both the small and large breast phantoms.

Radiotherapy for early infradiaphragmatic Hodgkin's disease: the Australasian experience.

PURPOSE: To review the Australasian results of Stage I and IIA Infradiaphragmatic Hodgkin's Disease (IHD) treated solely by irradiation. METHODS AND MATERIALS: Eligible patients had IHD only and were treated by irradiation with curative intent over the period of 1969 to 1988. Ten radiation oncology centres from within Australia and New Zealand were surveyed for patient, tumour and treatment variables. Disease free rates, survival and complications were analysed. RESULTS: 106 patients with IHD were studied. The average potential follow up was 9.4 years. The male to female ratio was 3.3:1. The median age was 37.5 years. Histological subgroups were as follows; lymphocyte predominant 43%, mixed cellularity 21%, lymphocyte depleted 5%, nodular sclerosing 27% and unclassifiable 4%. Fifty nine patients had laparotomy of which 22 (37%) were positive for tumour. Nine laparotomies were performed for diagnosis and the remainder for staging. One patient was up-staged by laparotomy and three were down-staged. Sixty-eight patients presented with inguinal disease alone, five with abdominal disease alone, 19 with two sites of involvement and 12 with inguinal, pelvic and abdominal disease. In two patients the site was unknown. There was no correlation between site of involvement, age, sex or histological subtype. Forty seven cases were clinically staged (CS) as follows: CS IA-23, CS IIA-24. The other 59 were pathologically staged (PS) as follows: PS IA-37, PS IB-1, PS IIA-21. Treatment consisted of involved field alone (16), inverted Y (68), inverted Y and spleen (13), para-aortic irradiation only (3), or total nodal irradiation (6). Mean dose was 37 Gy. There were 30 recurrences to give an acturial 10-year disease-free rate of 70%. In multivariate analysis lower number of tumour sites, lymphocyte predominant histology and higher dose were all significantly correlated with higher disease free rates. Eight patients died of Hodgkin's disease and 19 of other causes. The 10-year overall survival rate was 71%. Older age and higher number of disease sites were significantly correlated with shorter survival. Fourteen of 30 relapses may have been avoidable by the use of total nodal irradiation. In particular ten of 21 patients with abdominal disease relapsed in nodal sites which would have been covered by total nodal irradiation. CONCLUSIONS: The rate of control in IHD could perhaps be improved by avoiding involved field irradiation or by aggressive therapy with total nodal irradiation or combined modality chemo-irradiation in Stage II disease. Staging laparotomy does not appear to be indicated.