Older age and comorbidity in breast cancer: is RT alone the new therapeutic frontier?

AIM: To assess the impact of age, comorbidities and endocrine therapy (ET) in older breast cancer (BC) patients treated with hypofractionated radiotherapy (Hypo-RT). METHODS: From June 2009 to December 2017, we enrolled in this study 735 ER-positive BC patients (stage pT1-T2, pNx-1, M0 and age ≥ 65 years) receiving hypo-RT and followed them until September 2019. Baseline comorbidities included in the hypertension-augmented Charlson Comorbidity Index were retrospectively retrieved. Logistic regression model estimated adjusted-odds ratios (ORs) of ET prescription in relation to baseline patient and tumor characteristics. Competing risk analysis estimated 5-year cumulative incidence function (CIF) of ET discontinuation due to side effects (with BC progression or death as competing events), and its effect on locoregional recurrence (LRR) and distant metastasis (DM) (with death as competing event). RESULTS: ET has been prescribed in 89% patients. In multivariable analysis, the odds of ET prescription was significantly reduced in older patients (≥ 80 years, OR 0.08, 95% CI 0.03-0.20) and significantly increased in patients with moderate comorbidity. Patients ≥ 80 years discontinued the prescribed therapy earlier and more frequently than younger (65-69 years) patients (p = 0.060). Five-year CIF of LLR, DM and death from causes other that BC were 1.7%, 2.2% and 7.5%, respectively. Patients who discontinued ET had higher chance of LRR (p = 0.004). ET use did not impact on OS in any of the analyzed groups. CONCLUSIONS: In older patients, ET did not show a benefit in terms of overall survival. Further studies focusing on tailored treatment approaches are warranted to offer the best care in terms of adjuvant treatment to these patients.

VMAT partial-breast irradiation: acute toxicity of hypofractionated schedules of 30 Gy in five daily fractions.

PURPOSE: To report acute toxicities in breast cancer (BC) patients (pts) recruited in a prospective trial and treated with accelerated partial-breast irradiation (APBI) using Volumetric Modulated Arc Therapy (VMAT) delivered with a hypofractionated schedule. METHODS: From March 2014 to June 2019, pts with early-stage BC (Stage I), who underwent breast conservative surgery (BCS), were recruited in a prospective study started at the National Cancer Institute of Milan. Pts received APBI with a hypofractionated schedule of 30 Gy in five daily fractions. Radiotherapy treatment (RT) was delivered using VMAT. Acute toxicity was assessed according to RTOG/EORTC criteria at the end of RT. RESULTS: Between March 2014 and June 2019, 151 pts were enrolled in this study. 79 Pts had right-side and 72 had left-side breast cancer. Median age was 69 (range 43-92). All pts presented with pathological stage IA BC, molecular classification was Luminal A in 128/151 (85%) and Luminal B in 23/151 (15%) cases. Acute toxicity, assessed at the end of RT, consisted of G1 erythema in 37/151 (24. 5%) pts and skin toxicities higher than G1, did not occur. Fibrosis G1 and G2 were reported in 41/151 (27. 1%) pts and in 2/151 pts (1. 3%), respectively. Edema G1 occurred in 8/151 (5. 3%) pts and asthenia G1 occurred in 1/151 (0. 6%) pts. CONCLUSIONS: APBI with VMAT proved to be feasible and can be a valid alternative treatment option after BCS in selected early breast cancer pts according to ASTRO guidelines. A longer follow-up is needed to assess late toxicity.

International multidisciplinary expert panel consensus on breast reconstruction and radiotherapy.

BACKGROUND: Conflicting evidence challenges clinical decision-making when breast reconstruction is considered in the context of radiotherapy. Current literature was evaluated and key statements on topical issues were generated and discussed by an expert panel at the International Oncoplastic Breast Surgery Meeting in Milan 2017. METHODS: Studies on radiotherapy and breast reconstruction (1985 to September 2017) were screened using MEDLINE, Embase and CENTRAL. The literature review yielded 30 controversial key questions. A set of key statements was derived and the highest levels of clinical evidence (LoE) for each of these were summarized. Nineteen panellists convened for dedicated discussions at the International Oncoplastic Breast Surgery Meeting to express agreement, disagreement or abstention for the generated key statements. RESULTS: The literature review identified 1522 peer-reviewed publications. A list of 22 key statements was produced, with the highest LoE recorded for each statement. These ranged from II to IV, with most statements (11 of 22, 50 per cent) supported by LoE III. There was full consensus for nine (41 per cent) of the 22 key statements, and more than 75 per cent agreement was reached for half (11 of 22). CONCLUSION: Poor evidence exists on which to base patient-informed consent. Low-quality studies are conflicting with wide-ranging treatment options, precluding expert consensus regarding optimal type and timing of breast reconstruction in the context of radiotherapy. There is a need for high-quality evidence from prospective registries and randomized trials in this field.

ANTECEDENTES: El hecho de que la evidencia disponible sea conflictiva supone un reto para la toma de decisiones a la hora de considerar la reconstrucción mamaria en el contexto de radioterapia (radiotherapy, RT). En el seno de un panel de expertos reunidos durante el International Oncoplastic Breast Surgery Meeting celebrado en Milán en 2017, se revisó la literatura disponible y se generaron y discutieron los aspectos más relevantes. MÉTODOS: Se hizo una búsqueda bibliográfica de los estudios de RT y reconstrucción mamaria (1985-septiembre de 2017) en las bases MEDLINE, EMBASE y CENTRAL. La revisión de la literatura permitió identificar 30 cuestiones clave controvertidas. A partir de ellas, se construyeron una serie de afirmaciones, para las que se obtuvo el mayor nivel de evidencia (levels of clinical evidence, LoE) posible. El acuerdo, desacuerdo o abstención respecto a las cuestiones propuestas fueron el resultado de las discusiones de 19 expertos reunidos durante el International Oncoplastic Breast Surgery Meeting. RESULTADOS: Se identificaron 1.522 artículos publicados en revistas con peer review. Se elaboró una lista de 22 afirmaciones clave y se anotó el LoE más alto obtenido para cada una de ellas. El grado de variabilidad fue de II a IV, pero la mayoría de las afirmaciones (54,5%) obtuvieron un LoE III. Hubo un consenso total en el 41% (9/22) de las afirmaciones, mientras que se obtuvo más de un 75% de acuerdo en la mitad de las afirmaciones (11/22). CONCLUSIÓN: La evidencia en la que basar el consentimiento informado en estos pacientes es escasa. Se trata de estudios de baja calidad con gran variedad de opciones terapéuticas, que dificultan el consenso de los expertos acerca del tipo y momento óptimo para la reconstrucción mamaria en el contexto de RT. Para obtener datos de mayor calidad se precisan estudios prospectivos y ensayos clínicos en este campo.

Factors influencing acute and late toxicity in the era of adjuvant hypofractionated breast radiotherapy.

PURPOSE: To evaluate toxicity in breast cancer patients treated with anthracycline and taxane based chemotherapy and whole breast hypofractionated radiotherapy, and to identify the risk factors for toxicity. METHODS AND MATERIALS: 537 early breast cancer patients receiving hypofractionated radiotherapy after conservative surgery were enrolled from April 2009 to December 2014, in an Italian cancer institute. The dose was 42.4 Gy in 16 daily fractions, 2.65 Gy per fraction. The boost to the tumor bed was administered only in grade III breast cancer patients and in patients with close or positive margins. Acute and late toxicity were prospectively assessed during and after radiotherapy according to RTOG scale. The impact of patients clinical characteristics, performed treatments and dose inhomogeneities on the occurrence of an higher level of acute skin toxicity and late fibrosis has been evaluated by univariate and multivariate analysis. RESULTS: The mean age was 74 (range 46-91 yrs). 27% of patients received boost. 22% of cases (n = 119) received also chemotherapy. The median follow-up was 32 months. G1 and G2/G3 acute skin toxicity were 61.3% and 20.5% and G1 and G2/G3 late fibrosis 12.6% and 4.3% respectively. Chemotherapy (p = 0.04), diabetes (p = 0.04) and boost administration (p < 0.01) were found to be statistically significant on the occurrence of late fibrosis, but a multivariate analysis did not show any factors connected. The boost administration (p < 0.01), the breast volume (p = 0.05), dose inhomogeneities (p < 0.01) and boost volume (p = 0.04) were found to be statistically significant as concerns the occurrence of acute skin reaction at the univariate analysis, but only the boost administration (p = 0.02), at multivariate analysis. CONCLUSIONS: The results of our study, according to the large randomized trials, confirmed that hypofractionated whole breast irradiation is safe, and only the boost administration seems to be an important predictor for toxicity. Chemotherapy does not impact on acute and late skin toxicity.

Axillary dissection versus no axillary dissection in older T1N0 breast cancer patients: 15-year results of trial and out-trial patients.

BACKGROUND: Our randomized trial found no survival advantage for axillary dissection (AD) compared observation only (no AD) in older patients with early breast cancer and a clinically negative axilla, indicating that AD is unnecessary. We compared characteristics and outcomes in out-trial patients with those in trial patients to provide indications as to whether AD can be safely omitted outside the trial setting. METHODS: The trial started in 1996, recruiting 238 patients age 65-80 years with cT1cN0 breast cancer, randomized to conservative surgery with or without AD. Over the recruitment period, 109 eligible patients who refused to participate in the trial, also received conservative breast surgery with or without AD depending on patient preference/surgeon opinion. Trial and out-trial patients received conventionally-fractioned whole breast radiation and tamoxifen for five years. Endpoints were breast cancer mortality, overall survival, and cumulative incidence of axillary disease in patients not receiving AD. RESULTS: After 15 years of follow-up, breast cancer mortality and overall survival did not differ between the AD and no AD arms, in either the trial or out-trial cohorts. The 15-year cumulative incidence of axillary relapse was 6% in the no AD arm of the trial group, and zero in the no AD arm of the out-trial group. CONCLUSIONS: Outside the trial setting, older patients with T1N0 breast cancer can be safely treated by conservative surgery, postoperative radiotherapy and tamoxifen for five years (if ER-positive). Axillary surgery is appropriate only for the small proportion of patients who develop overt axillary disease during follow-up.

Control of human cytomegalovirus infection in patients infected with human immunodeficiency virus by high levels of specific CD8+ T-cells.

A new technique was used to simultaneously determine human cytomegalovirus (HCMV)-specific CD4(+) and CD8(+) T-cells in highly active anti-retroviral therapy (HAART)-naive and HAART-treated patients infected with human immunodeficiency virus (HIV). HIV-infected patients with HCMV infection, but without HCMV disease, showed low numbers of HCMV-specific CD4(+) cells and high numbers of CD8(+) T-cells, both before and during HAART. HIV-infected patients with HCMV disease had no HCMV-specific CD4(+) T-cells and extremely low levels of CD8(+) T-cells. Resolution of disease during HAART was associated with rescue of specific CD4(+) T-cells and a large increase in the specific CD8(+) T-cell count. Thus, HAART does not completely restore the normal immune function. In HIV-infected patients, sustained control of HCMV infection requires high frequencies of specific CD8(+) T-cells.

Monitoring of human cytomegalovirus-specific CD4 and CD8 T-cell immunity in patients receiving solid organ transplantation.

Absolute and human cytomegalovirus (HCMV)-specific CD4+ and CD8+ T-cell counts were monitored in 38 solid organ (20 heart, 9 lung and 9 kidney) transplant recipients during the first year after transplantation by a novel assay based on T-cell stimulation with HCMV-infected autologous dendritic cells. According to the pattern of T-cell restoration occurring either within the first month after transplantation or later, patients were classified as either early (n = 21) or late responders (n = 17). HCMV-specific CD4+ and CD8+ T-cell counts were consistently lower in late compared to early responders from baseline through 6 months after transplantation. In addition, in late responders, while HCMV infection preceded immune restoration, HCMV-specific CD4+ restoration was significantly delayed with respect to CD8+ T-cell restoration. The number of HCMV-specific CD4+ and CD8+ T-cells detected prior to transplantation significantly correlated with time to T-cell immunity restoration, in that higher HCMV-specific T-cell counts predicted earlier immune restoration. Clinically, the great majority of early responders (18/21, 85.7%) underwent self-resolving HCMV infections (p = 0.004), whereas the great majority of late responders (13/17, 76.5%) were affected by HCMV infections requiring antiviral treatment (p = <0.0001). Simultaneous monitoring of HCMV infection and HCMV-specific T-cell immunity predicts T-cell-mediated control of HCMV infection.

Status of surgical margins and prognosis in adult soft tissue sarcomas of the extremities: a series of patients treated at a single institution.

PURPOSE: To explore the prognostic effect of microscopic marginal status after surgery for extremity soft tissue sarcomas. PATIENTS AND METHODS: We analyzed 911 consecutive patients surgically treated throughout a 20-year span at a single referral center. Six hundred forty-two were first seen with a primary tumor, and 269, with a locally recurrent tumor. All patients underwent macroscopically complete resection. Microscopic marginal status was negative (tumor size > 1 mm) in 748 patients and positive (

Chordoma: natural history and results in 28 patients treated at a single institution.

BACKGROUND: The natural history of chordoma is characterized by a high failure rate and a poor functional outcome. The purpose of this study was to review the long-term outcome of our institutional experience. METHODS: The clinical features, type of treatment, pathologic assessment, and follow-up of 56 consecutive patients with chordoma were reviewed. RESULTS: Fifty sacral and six mobile spine chordomas (median size, 13 cm; range, 2-30 cm) were treated at our center between January 1933 and December 2000. Twenty-eight patients affected by sacrococcygeal chordoma and operated on after 1977 form the basis of our study. Surgical margins were rated as wide in 11 cases, marginal in 13 cases, and intralesional in 4 cases. The median follow-up was 71 months (range, 15-200 months). Seventeen patients' disease recurred. Ten patients died as a result of disease. Nine patients remained continuously free of disease. The estimated 5- and 10-year overall survival was, respectively, 87.8% and 48.9%; disease-free survival was 60.6% and 24.2%. Radiotherapy was considered for marginal and intralesional resections. CONCLUSIONS: High sacral amputation can achieve a good rate of wide-margin resections for sacrococcygeal chordomas. Adjuvant radiotherapy may offset the negative effect in the prognosis of marginal resections.

Quality of surgery and outcome in extra-abdominal aggressive fibromatosis: a series of patients surgically treated at a single institution.

PURPOSE: To explore prognostic factors in surgically treated aggressive fibromatosis (extra-abdominal desmoid tumor). PATIENTS AND METHODS: A total of 203 consecutive patients treated with surgery over a 35-year period at a single referral center were retrospectively reviewed. One hundred twenty-eight were first seen at our institution with primary disease, whereas 75 had a recurrent tumor. All patients underwent macroscopically complete resection. Margins were rated as negative in 146 (97 with primary tumors, 49 with recurrences) and positive in 57 (31 in primary, 26 in recurrences) patients. Median follow-up was 135 months. RESULTS: Patients with primary disease had a better disease-free survival rate than those with recurrence (76% v 59% at 10 years). Presenting with a recurrence was also the strongest predictor of local failure in the multivariate analysis. In patients first treated for primary disease, size and site had prognostic significance, whereas microscopically positive surgical margins did not. In contrast, in patients with recurrence, there was a trend toward better prognosis if margins were negative (although this was not significant at multivariate analysis). CONCLUSION: Presence of microscopic disease does not necessarily affect long-term disease-free survival in patients with primary presentation of extra-abdominal desmoid tumors. Thus, function-sparing surgery may be a reasonable choice when feasible without leaving macroscopic residual disease. In patients with recurrences, positive margins may more clearly affect prognosis, potentially necessitating adjuvant radiation in selected cases.

Cytotoxic chemotherapy preceding apheresis of peripheral blood progenitor cells can affect the early reconstitution phase of naive T cells after autologous transplantation.

Transient T cell immunodeficiency is a common complication following hematopoietic stem cell transplantation. In breast cancer patients transplanted with autologous peripheral blood progenitor cells (PBPC) harvested after cytotoxic treatment with either cyclophosphamide or epirubicin plus paclitaxel, we evaluated T cells infused in grafts and in peripheral blood during the early reconstitution phase. We found that PBPC grafts harvested after treatment with epirubicin plus paclitaxel contained substantially larger numbers of T cells with less altered composition than after cyclophosphamide. Three months after high-dose cytotoxic chemotherapy, the numbers and the kinetics of circulating naive T cells, but not of memory and CD28- T cells, correlated positively with the number of naive T cells infused PBPC grafts. Finally, retrospective analysis of two cohorts of patients transplanted in different clinical settings with PBPC grafts harvested following cyclophosphamide or epirubicin plus paclitaxel showed apparently different susceptibilities to develop endogenous varicella zoster virus reactivation in the first year after high-dose cytotoxic chemotherapy. On the whole, these data indicate that number and composition of T cells in PBPC grafts vary according to the former cytotoxic therapy, and suggest that autologous transfer of T cells may accelerate the early T cell reconstitution phase and possibly ameliorate immune competence in patients rendered lymphopenic by high-dose chemotherapy.

Circulating CD33+ large mononuclear cells contain three distinct populations with phenotype of putative antigen-presenting cells including myeloid dendritic cells and CD14+ monocytes with their CD16+ subset.

BACKGROUND: In peripheral blood, myeloid markers identify a heterogeneous mixture of cells in transit from the bone marrow to peripheral tissues. Similarly, HLA-class II DR expression usually identifies mononuclear cells with the potential for developing antigen-presenting activity. We gathered putative antigen presenting cells bearing myeloid markers (My-APC) to study their composition by cell surface phenotype. METHODS: To gather and dissect My-APC phenotype while excluding lymphocytes and granulocytes, we developed a strategy based on staining red cell-lysed peripheral blood and gating cells bearing myeloid markers and physical parameters of large mononuclear cells. RESULTS: Phenotypic analysis within the My-APC gate showed three distinct populations. The largest fraction was constituted by CD14+ monocytes that extended into the other two populations, each expressing gradually lower levels of CD14 surface antigen along with increasing levels of CD16 and CD2, respectively. The CD16 and CD2 expression patterns extended from CD16+CD14+ or CD2+CD14+ double- positive intermediate cells toward each single positive subset, but they were reciprocally exclusive. Interestingly, CD2+CD14- cells within the My-APC gate were equivalent to myeloid dendritic cell precursors (pre-DC) defined previously by the absence of lineage markers and expression of HLA-DR and myeloid markers. Phenotypic analysis of each population revealed differences in the expression of costimulatory molecules and CD62L. CONCLUSIONS: This novel analytical approach allowed us to distinguish circulating My-APC in three subsets and to identify relationships between monocytes and other related myeloid populations including DC.

Ocular metastases from breast carcinoma: A multicentric retrospective study.

Breast cancer may affect the eye and orbit by metastatic neoplastic infiltration, uvea being the most common site of presentation. Management of these cases with radiotherapy is usually gratifying with reported response rate of approximately 75%. A retrospective evaluation of cases treated in five Institutions participating in a collaborative radiation therapy group of north-Italy is reported. Fifty-four cases of metastases to the eye or orbit were referred for radiation therapy to the Departments participating in the survey in the period 1977-1995. There were 49 female patients aged between 28 and 75 years (median, 44 years) at presentation of orbital metastasis. Thirty-eight lesions (70%) were metastases to the choroid, 9 involved other parts of the eye, and 7 patients had orbital metastases. Five of the 49 patients had bilateral choroidal metastases. Radiotherapy was employed with megavoltage equipment. The median total dose delivered was 40 Gy (range, 16-60 Gy). All the patients were treated 5 times per week with fraction sizes ranging from 1.8 to 3.0 Gy (median, 2.0 Gy). Of the 43 evaluable eyes, 34 (79%) showed a definite improvement after radiotherapy. There was a stabilization of the process in 4 patients. The rest (11 lesions) were lost to detailed follow-up of the response of the eye metastases. Twelve patients experienced acute transient cheratoconjunctivitis and in a case a subconjunctival haemorrhage was observed; as late side effects, two cases of chataract were observed during a period of observation of 37 and 117 months. A median survival time of 17 months was observed. The goal of irradiation was to improve vision or at least prevent blindness and enucleation. The palliative effect of irradiation was confirmed with a response rate consistent with the data of the literature on this subject.

Long-term results of sequential chemotherapy-radiotherapy-chemotherapy in locally advanced squamous cell carcinoma of the uterine cervix.

PURPOSE OF INVESTIGATION: In order to evaluate the impact of sequential chemotherapy-radiotherapy-chemotherapy on local control and survival, a follow-up study was carried out 12 years after the treatment of 22 patients with FIGO stage IIB-III squamous cell cervical cancer. METHODS: Patients were submitted to three cycles of induction chemotherapy (cisplatin and bleomycin) followed by whole pelvis irradiation and central boost with endocavitary brachytherapy. Ten patients underwent three further cycles of chemotherapy after radiotherapy. All patients were maintained by regular follow-up. Only one patient was lost 48 months after treatment. RESULTS: At the end of treatment complete response was obtained in 14 patients (63.5%). Four of these recurred locally, and one at also distance. Eight patients failed to obtain a complete response. Twelve patients died from disease and one patient died from other causes. Nine of 22 (41%) patients are alive without evidence of disease with a median follow-up of 134 months. Acute toxicity was mild, while two severe late complications were observed. CONCLUSIONS: The achievement of complete remission at the end of treatment is important in terms of life expectancy. Further chemotherapy appears useful for patients who do not reach complete local remission after radiotherapy.

Radio-chemotherapy of anal cancer.

Conventional treatment of anal cancer has been the demolitive Miles operation for decades. Radiotherapy has been utilized in a limited number of centers for early cancers only. Radio-chemotherapy has become the treatment of choice for all stages of anal cancer after the first experiences by the group of Detroit and after the confirmation of successful results by many other centers. Infusional chemotherapy (5-FU and Mitomycin C or CDDP) and concurrent irradiation are able to achieve local control in more than 80% of patients. Surgery currently represents a rescue treatment for partial responders or in relapsing patients. A brief review of the literature and the experience at the Istituto Tumori in Milano are presented.

Radio-chemotherapy of vulvar cancer.

Surgery alone, more or less demolitive, is the treatment of choice of vulvar cancers. Cure rates are high for early cancers only, while locally advanced tumors with or without inguinal adenopathies and recurrences have a bad prognosis. The excellent results of concurrent chemo-radiotherapy of anal cancers suggested to adopt the same approach for locally advanced vulvar cancers. The shrinkage of the tumor allowed surgery, often less demolitive than usual, and the pathological examination demonstrated an overall complete response in 40% of cases. Survival has been improved through this multidisciplinary approach. Patients not suitable for surgery obtained important remissions and an improved quality of life. Clinical experience at the Istituto Tumori of Milano is presented.

Early breast cancer: evaluation of the prognostic role of the site of the primary tumor.

PURPOSE: The prognostic role of the site of the primary breast cancer has not been clarified. This study aimed to gather more information about this issue from a large series of patients with long-term follow-up data. PATIENTS AND METHODS: Data from 2,396 patients treated for early breast cancer with a conservative approach were reviewed (1973 to 1989). In 1,619 patients, the tumor had a lateral site, while in 777 cases, it was situated in the internal/central quadrants. The characteristics of the two groups were well balanced, apart from axillary nodal metastases, which were more frequent for lateral tumors (38.1% v 26.3%). RESULTS: Analysis of distant metastases indicated that the regression coefficient associated with tumor site was significant and the hazards ratio estimate was 1.291, which indicates the risk of distant metastases was increased by approximately 30% for internal/central tumors. The analysis of overall survival yielded a significant coefficient and a hazards ratio of 1.192, which indicates an approximately 20% increase of mortality for internal/central tumors. CONCLUSION: Early breast cancers situated in central/ internal quadrants have a worse prognosis compared with those in lateral quadrants, in terms of distant metastases and survival. Irradiation of the internal mammary chain for internal/medial tumors could be suggested, but, to date, the therapeutic strategy is still controversial.

Analysis of risk factors for mandibular bone radionecrosis after exclusive low dose-rate brachytherapy for oral cancer.

BACKGROUND: Brachytherapy is widely adopted as an exclusive treatment of T1/T2 oral cancer with a high probability of definitive cure. Therefore, any major complication, like mandibular bone necrosis, should be avoided. Many risk factors, either clinical or technical, have been considered in the literature. MATERIALS AND METHODS: One hundred consecutive interstitial iridium LDR treatments for early cancers of the tongue and floor of the mouth performed from January 1989 to November 1993 were reviewed. An analysis of some simple technical parameters (total dose, dose-rate, reference volume, linear activity, total reference kerma) was performed in order to identify the main physical risk factors. Moreover, total dose was recalculated as extrapolated responsive dose for normal tissue complications. RESULTS: Bone necrosis was observed in 10 out of 100 patients with a median follow-up of 38 months. No significant incidence of this complication was observed when tumor site (mobile tongue versus floor of the mouth), dental status or total physical dose were considered. A significant correlation between the incidence of bone necrosis and two main parameters was found, i.e. dose-rate (P < 0.02) and reference volume (P < 0.05). CONCLUSIONS: A threshold value may be suggested both for dose-rate (50 cGy/h) and reference volume (25,000 mm3). Bone necrosis is clearly related to both these parameters since most cases (i.e. 80%) were observed in the subgroup over the volume and dose-rate threshold.

Cancer of the uterine cervix: clinical value of squamous cell carcinoma antigen (SCC) measurements.

The clinical value of SCC levels has been evaluated in four groups of women affected by cervical carcinoma. Among the 116 newly diagnosed patients, the SCC pretreatment level was elevated in 57% of cases and was strictly correlated with clinical stage (Ib to IV: p = < 0.01) and histotype (squamous cell carcinoma versus others: p = 0.0005). No significant difference was found in relation to nodal status. For the 28 patients submitted to neoadjuvant chemotherapy clinical response was correlated with the change in serum SCC level: stable or rising serum level indicated that the disease was unchanged or progressive, respectively. In the group of 48 patients affected by recurrent carcinoma, a raised SCC level was found in 71% of cases, with a lead time ranging from 0 to 12 months. No identification of the site of recurrence could be extrapolated from the value of SCC. As to the 108 regularly monitored patients, no significant difference in the risk to develop recurrence was shown for patients with a raised SCC level at the time of primary diagnosis (NED) versus relapsed: p = > 0.05).

Current controversies in the therapeutic approach to early breast cancer in the elderly.

Over a 7-year period, in 408 patients aged 70 years or more, 413 early breast cancers were treated as follows: quadrantectomy, axillary dissection, and radiotherapy (QUART) in 142 patients, wide lumpectomy plus radiotherapy extended to the axilla in case of palpable nodes (WLRT) in 45 patients and wide lumpectomy alone in 221 patients. Postoperative tamoxifen was given to 251 patients and chemotherapy to 31. Mean follow-up was 54 months. Relapse free survival was similar at 5 years in the three groups (80%); at 10 years it was 80.8% in QUART, 61.3% in WLRT, 51.7% in WL. Locoregional recurrence, as first failure, occurred in 1.4% QUART, 6.5% WLRT and 15.2% WL. In our experience compliance with surgical day-hospital regimen was excellent, while postoperative radiotherapy created some problems, mainly among oldest patients. We support the role of radiotherapy for its positive impact on local control.