G. Biti

Circulating Tumour Cells in locally advanced head and neck cancer: Preliminary report about their possible role in predicting response to non-surgical treatment and survival

BACKGROUND AND PURPOSE The mechanism of dissemination of locally advanced head and neck cancer (LAHNC) is far to be resolved. Circulating tumour cells (CTC) have been identified as a prognostic factor in metastatic breast and prostate cancer. This prospective multi-centric analysis studied the possible role of CTC identification in LAHNC. MATERIALS AND METHODS CTC were searched in 73 patients with LAHNC (oropharynx, n=39; nasopharynx, n=10; larynx, n=10; paranasal sinuses, n=6, of whom 3 with sinonasal undifferentiated carcinoma, SNUC; hypopharynx, n=5; oral cavity, n=3). All of them (apart from SNUC) had squamous cell cancers. The relationship between CTC positivity and other clinical prognostic factors has been investigated. Response to treatment and survival has been related with changes in CTC number during the treatment. RESULTS CTC were frequently identified in oro- and hypopharyngeal cancer and in SNUC. They were more frequent in stage IV than in stages I-III disease (18% versus 6%, p=NS (not significant)). Partial or complete response (CR) was related with the absence or disappearance of CTC during treatment (p=0.017). A decrease in the CTC number or their absence throughout the treatment seems also related with non-progressive disease, after both complete or incomplete remission and with the proportion of patients alive and NED (no evidence of disease) (p=0.009). CONCLUSIONS These preliminary data suggest a possible role of CTC determination in head and neck cancer. Additional and longer follow up data need to be collected to confirm these findings.

Abnormalities of in vitro immunoglobulin synthesis by peripheral blood lymphocytes from untreated patients with Hodgkin's disease.

The immunoglobulin-synthesizing activities of peripheral blood mononuclear cells from 57 untreated patients with Hodgkins disease and 47 normal subjects were compared. Cumulative amounts of IgM and IgG synthesized and secreted by unstimulated and pokeweed mitogen-stimulated cells over a 7-d period were determined in a solid-phase radioimmunoassay. Synthesis of IgM in unstimulated cultures and of both IgM and IgG in cultures stimulated with pokeweed mitogen was markedly reduced in patients with Hodgkins disease, whereas the mean level of the spontaneous IgG synthesis was enhanced. The degree and frequency of in vitro abnormalities were not influenced by disease stage or histology. Depression of pokeweed mitogen-induced immunoglobulin synthesis did not correlate with excessive number of monocytes and it was unaffected by removal of phagocytic cells or addition to the cultures of monocytes from normal individuals. On the other hand, monocytes isolated from blood of patients with Hodgkins disease were even more effective than normal monocytes in supporting pokeweed mitogen-induced immunoglobulin synthesis by normal phagocyte-depleted mononuclear cells. Synthesis of both IgM and IgG induced by pokeweed mitogen remained subnormal after addition to patient B cell cultures of autologous irradiated T cells or allogeneic normal T lymphocytes. T cells from patients with Hodgkins disease appeared at least as effective as normal T cells in helping pokeweed mitogen-induced immunoglobulin production by normal B cells. However, when normal T cells were co-cultured with B cells from patients with Hodgkins disease, spontaneous IgG synthesis declined, whereas the addition of patient T cells to normal B cells resulted in an increase of spontaneous IgG synthesis. In patients showing depression of pokeweed mitogen-induced immunoglobulin synthesis the lymphoproliferative response and immunoglobulin synthesis stimulated by Staphylococcus aureus bacteria of the Cowan first strain, a T cell independent B cell mitogen, were also markedly reduced. These studies demonstrate impairment of immunoglobulin synthesis by cultured lymphocytes from untreated patients with Hodgkins disease after stimulation with polyclonal B cell activators and suggest that the in vitro abnormalities may be, at least in part, the result of a preexisting in vivo activation of lymphocytes in Hodgkins disease patients.

Circulating Tumor Cells in Patients with Recurrent or Metastatic Head and Neck Carcinoma: Prognostic and Predictive Significance

Introduction We investigated the frequency of detection and the prognostic and predictive significance of circulating tumor cells (CTCs) in patients with recurrent/metastatic (R/M) head and neck carcinoma (HNC) before starting systemic therapy. Patients and methods Using the CellSearch technology, CTCs were assessed prospectively in peripheral blood of 53 R/M-HNC patients. We performed spiking experiments to test the diagnostic performance of the CellSearch platform in identifying squamous carcinoma cells. Results CTCs were identified in 14 (26%) and 22 (41%) patients at baseline and at any time point, respectively. In univariate analysis ≥2 CTCs had a poorer prognostic role than 0–1 CTC. In multivariate analysis, the presence of one CTC or more was associated with a poor prognosis both in terms of progression-free survival (PFS) [Hazard Ratio (HR): 3.068, 95% confidence interval (CI): 1.53–6.13, p 0.002] and overall survival (OS) [HR: 3.0, 95% CI: 1.48–6.0, p 0.002]. A disease control after systemic therapy was obtained in 8% of CTC-positive patients as opposed to 45% in CTC-negative ones (p 0.03). The epidermal growth factor receptor (EGFR) expression was identified in 45% of CTC-positive patients. Discussion In conclusion, CTCs are detected in one out of three patients with RM-HNC. CTC detection is a strong prognostic parameter and may be predictive of treatment efficacy. The frequency of EGFR expression in CTCs seems to be lower than that expected in the primary tumor.

Breast Cancer in the Elderly: Treatment of 1500 Patients

Abstract:  There is a significant difference in the extent of treatment offered to the elderly with breast cancer; in the United States, while 98% of patients less than 65 years of age receive standard treatment, 81% of those older than 65 years were treated according to protocol. This studys goal was to evaluate disease‐specific survival and local‐regional recurrence in breast cancer patients more than 65 years of age at diagnosis. A total of 1500 patients with invasive breast carcinoma were treated consecutively from May 1971 to July 2002 at the University of Florence, Florence, Italy. All patients were more than 65 years of age. The median age was 70.6 years (range 65.1–87.3 years).The median follow‐up was 8.7 years (range 1–30 years). The crude probability of survival (or relapse occurrence) was estimated using the Kaplan–Meier method and survival (or relapse occurrence) comparisons were carried out using Cox proportional hazard regression models. The Cox regression model by stepwise selection showed as independent prognostic factors for disease‐specific survival (DSS), the occurrence of a local relapse (p < 0.0001), pN status (p < 0.0001), the type of surgery (p < 0.0001), and the use of radiotherapy (p < 0.0006) and chemotherapy (p = 0.01). For local disease‐free survival (LDFS), the Cox regression model by stepwise selection showed that mastectomy (p < 0.0001), histotype (p < 0.0001), pN status (p < 0.0001), and pT status (p = 0.001) were the only independent prognostic factors. Age was not a prognostic factor for DSS nor LDFS. We suggest treating patients with appropriate treatment for their prognostic factors. 

ACCELERATED INTENSITY-MODULATED EXTERNAL RADIOTHERAPY AS A NEW TECHNICAL APPROACH TO TREAT THE INDEX QUADRANT AFTER CONSERVING SURGERY IN EARLY BREAST CANCER: A PRELIMINARY STUDY

Purpose We present a novel technical approach to treat the index quadrant after conserving surgery in patients with early breast cancer and study its clinical feasibility. Methods and material Patients selected for the study, after breast conserving surgery with histologically verified breast carcinoma, signed a full informed consent to intensity-modulated external radiotherapy of the partial breast. Treatment was performed with the 6 MV beam from one of the Elekta Precise LINAC units installed in our Department. The prescribed dose was 30 Gy in 5 fractions in 10 days. Results Acute toxicity was minimal. No skin changes were noted during treatment or during the first 6 months after radiotherapy treatment. Conclusions Accelerated partial breast irradiation using intensity-modulated external radiotherapy is technically feasible. We think the approach will give good results in terms of local control, toxicity and quality of life, at the same time sparing resources for the patient and health care system.

Merkel cell carcinoma and iodine-131 metaiodobenzylguanidine scan

Two cases of Merkel cell carcinoma, a neuroendocrine neoplasia of the skin, investigated with iodine-131 metaiodobenzylguanidine (131i-mIBG) scintigraphy, are reported. Uptake in the tumor was evident only in 1 case. The possible diagnostic and therapeutic role of 131I-mIBG in patients with this rare neoplasm is discussed.

Ischemic stroke during cisplatin-based chemotherapy for testicular germ cell tumor: case report and review of the literature.

Abstract Testicular germ-cell tumors are the most common solid tumor in young men, with an incidence peak between the ages of 20 and 35 years. Even if rare, arterial thromboembolism is a serious and possible complication during cisplatin-based chemotherapy in young patients. The strong association between rapid treatment and favorable outcome is well known. Oncologists need to recognize the symptoms and to alert a stroke unit as soon as possible. We report the management of a young patient affected by non seminomatous testicular neoplasm without cardiovascular risk factors who developed an ischemic stroke during cisplatin-based treatment. We also review the relevant literature.

Treatment of invasive male breast cancer: a 40-year single-institution experience.

PurposeWe conducted a retrospective analysis to evaluate the management and outcome of invasive male breast cancer treated in a single-institution over a period of 40 years.Materials and methodsWe reviewed the clinical and pathological features of 60 male patients affected by breast carcinoma treated at our Radiotherapy Unit between 1971 and 2011. Tumours were classified according to histological type and the updated 2010 TNM classification of malignant tumours.ResultsAt a median follow-up of 8.9 [range, 0.6–20; standard deviation (SD), 4.98] years, 32 patients (53.3%) were alive and 16 patients died (26.7%) due to disease progression and 12 (20%) due to other causes. At univariate analysis for overall survival, pathological tumour size (p=0.031), histological subtype (p=0.013) and nodal status (p=0.006) emerged as significant predictors of death. At multivariate analysis, independent death predictors were advanced pathological tumour size (p=0.016), positive nodal status (p=0.003) and invasive cribriform histological type (p=0.0003).ConclusionsIn consideration of the rarity of the disease, many issues are still being debated, and future collaborative studies are required. However, our experience confirms the prognostic role of greater pathological tumour size and positive nodal status as unfavourable features for survival in male breast cancer.RiassuntoObiettivoAbbiamo condotto un’analisi retrospettiva per valutare il trattamento e la sopravvivenza di una serie di pazienti affetti da carcinoma mammario invasivo maschile trattati in un singolo centro in un periodo di 40 anni.Materiali e metodiAbbiamo analizzato le caratteristiche clinico-patologiche di 60 pazienti affetti da carcinoma mammario maschile trattati presso la nostra unità di radioterapia in un periodo compreso tra il 1971 ed il 2011. Le neoplasie sono state classificate in accordo con la variante istologica e la classificazione aggiornata TNM 2010 dei tumori maligni.RisultatiAd un follow-up mediano di 8,9 anni [range 0,6–20; deviazione standard (SD) 4,98], 32 pazienti (53,3%) risultano viventi, mentre 16 (26,7%) sono deceduti a causa della malattia e 12 (20%) per altre cause. All’analisi univariata per sopravvivenza assoluta, le dimensioni patologiche del tumore (p=0,031), l’istologia (p=0,013) e lo stato linfonodale (p=0,006) sono emersi quali significativi predittori di morte. All’analisi multivariata, risultano fattori prognostici indipendenti le maggiori dimensioni patologiche del tumore (p=0,016), lo stato linfonodale positivo (p=0,003) e l’istologia cribriforme invasiva (p=0,0003).ConclusioniIn considerazione della rarità della patologia, molti sono i temi ancora dibattuti e necessitano futuri studi collaborativi. La nostra esperienza conferma tuttavia l’impatto prognostico sfavorevole delle dimensioni patologiche del tumore e dello stato linfonodale positivo.Purpose. We conducted a retrospective analysis to evaluate the management and outcome of invasive male breast cancer treated in a single-institution over a period of 40 years. Materials and methods. We reviewed the clinical and pathological features of 60 male patients affected by breast carcinoma treated at our Radiotherapy Unit between 1971 and 2011. Tumours were classified according to histological type and the updated 2010 TNM classification of malignant tumours. Results. At a median follow-up of 8.9 [range, 0.6–20; standard deviation (SD), 4.98] years, 32 patients (53.3%) were alive and 16 patients died (26.7%) due to disease progression and 12 (20%) due to other causes. At univariate analysis for overall survival, pathological tumour size (p=0.031), histological subtype (p=0.013) and nodal status (p=0.006) emerged as significant predictors of death. At multivariate analysis, independent death predictors were advanced pathological tumour size (p=0.016), positive nodal status (p=0.003) and invasive cribriform histological type (p=0.0003). Conclusions. In consideration of the rarity of the disease, many issues are still being debated, and future collaborative studies are required. However, our experience confirms the prognostic role of greater Riassunto Obiettivo. Abbiamo condotto un’analisi retrospettiva per valutare il trattamento e la sopravvivenza di una serie di pazienti affetti da carcinoma mammario invasivo maschile trattati in un singolo centro in un periodo di 40 anni. Materiali e metodi. Abbiamo analizzato le caratteristiche clinico-patologiche di 60 pazienti affetti da carcinoma mammario maschile trattati presso la nostra unità di radioterapia in un periodo compreso tra il 1971 ed il 2011. Le neoplasie sono state classificate in accordo con la variante istologica e la classificazione aggiornata TNM 2010 dei tumori maligni. Risultati. Ad un follow-up mediano di 8,9 anni [range 0,6– 20; deviazione standard (SD) 4,98], 32 pazienti (53,3%) risultano viventi, mentre 16 (26,7%) sono deceduti a causa della malattia e 12 (20%) per altre cause. All’analisi univariata per sopravvivenza assoluta, le dimensioni patologiche del tumore (p=0,031), l’istologia (p=0,013) e lo stato linfonodale (p=0,006) sono emersi quali significativi predittori di morte. All’analisi multivariata, risultano fattori prognostici indipendenti le maggiori dimensioni patologiche del tumore (p=0,016), lo stato linfonodale positivo (p=0,003) e l’istologia cribriforme invasiva (p=0,0003). Conclusioni. In considerazione della rarità della patologia, molti sono i temi ancora dibattuti e necessitano RADIOTHERAPY RADIOTERAPIA Treatment of invasive male breast cancer: a 40-year single-institution experience Il trattamento del carcinoma mammario invasivo maschile: 40 anni di esperienza in un singolo centro I. Meattini1 • L. Livi1 • D. Franceschini1 • C. Saieva2 • V. Scotti1 • D. Casella3 • V. Criscenti3 I. Zanna2 • F. Meacci1 • E. Gerlain2 • B. Agresti1 • M. Mangoni1 • F. Paiar1 • G. Simontacchi1 D. Greto1 • J. Nori4 • S. Bianchi5 • L. Cataliotti3 • G. Biti1 Radiotherapy Unit, Department of Medical and Surgical Critical Care, University of Florence, Florence, Italy Molecular and Nutritional Epidemiology Unit, ISPO (Cancer Research and Prevention Institute), University of Florence, Florence, Italy Department of Surgery, Department of Medical and Surgical Critical Care, University of Florence, Florence, Italy Diagnostic Senology Unit, Department of Medical and Surgical Critical Care, University of Florence, Florence, Italy Division of Pathological Anatomy, Department of Medical and Surgical Critical Care, University of Florence, Florence, Italy Correspondence to: Icro Meattini, Radiotherapy Unit, University of Florence, Largo G.A. Brambilla 3, 50134 Florence, Italy Tel.: +39-055-7947719, Fax: +39-055-4379930, e-mail: icro.meattini@unifi.it Received: 9 October 2011 / Accepted: 4 December 2011 / Published online: 9 August 2012

Concomitant adjuvant chemo-radiation therapy with anthracyclinebased regimens in breast cancer: a single centre experience

Purpose. This study was done to evaluate the toxicity related to concurrent radiotherapy and anthracycline (AC)based chemotherapy in the adjuvant treatment of early breast cancer and to investigate the impact of treatment interruptions and the feasibility of this uncommon therapeutic approach.PurposeThis study was done to evaluate the toxicity related to concurrent radiotherapy and anthracycline (AC)-based chemotherapy in the adjuvant treatment of early breast cancer and to investigate the impact of treatment interruptions and the feasibility of this uncommon therapeutic approach.Materials and methodsFrom September 2002 to December 2007, 60 patients were treated at our Centre. The mean age at presentation was 48.5 (range 38–64) years. All patients underwent conservative surgery, and radiotherapy to the entire breast (mean dose 50 Gy; range 46–52 Gy). AC-based regimens consisted of four cycles of AC (doxorubicin plus cyclophosphamide) or four cycles of epirubicin (EPI) followed by four courses of cyclophosphamide, methotrexate and 5-fluorouracil (CMF).ResultsConcomitant treatment caused acute skin G3 toxicity in 8.9% of patients and one case of G4 toxicity (1.7%). Concerning cardiac assessment, six of the 56 evaluable patients (10.7%) developed an asymptomatic decline of left ventricular ejection fraction >10% and <20% of the baseline value. Radiotherapy was temporarily stopped in 21.3% and chemotherapy in 57.1% of patients.ConclusionsIn our experience, concomitant chemotherapy did not emerge as a significant factor in radiotherapy interruption. Moreover, no severe cardiac events were recorded.RiassuntoObiettivoScopo del nostro lavoro è stato valutare la tossicità associata al trattamento adiuvante concomitante radio-/chemioterapico, con chemioterapia a base di antracicline, nel carcinoma mammario, nonché analizzare l’impatto della chemioterapia sulle interruzioni del trattamento radiante e pertanto sulla fattibilità di questo non comune approccio terapeutico.Materiali e metodiDa settembre 2002 a dicembre 2007, 60 pazienti sono stati trattati presso il nostro Centro. L’età media alla diagnosi è stata di 48,5 anni (range 38–64). Tutti i pazienti sono stati sottoposti a chirurgia mammaria conservativa e radioterapia adiuvante sul corpo mammario (dose media 50 Gy; range 46–52 Gy). I regimi chemioterapici utilizzati a base di antracicline sono stati: quattro cicli di doxorubicina e ciclofosfamide (AC) oppure quattro cicli di epirubicina (EPI) seguiti da quattro cicli di ciclofosfamide, methotrexate e 5-fluoro uracile (CMF).RisultatiIl trattamento concomitante ha causato tossicità cutanea acuta G3 nell’8,9% dei pazienti e in un solo caso (1,7%) tossicità G4. Per quanto riguarda la tolleranza cardiologica, sei dei 56 pazienti valutabili (10,7%) hanno sviluppato un decremento asintomatico della frazione di eiezione ventricolare sinistra compreso tra il 10% e il 20% (dall’inizio del trattamento). Il trattamento radiante è stato temporaneamente interrotto nel 21,3% dei casi e il trattamento chemioterapico nel 57,1% dei casi.ConclusioniNella nostra esperienza la chemioterapia concomitante alla radioterapia non ha influenzato significativamente le possibili sospensioni per tossicità della radioterapia. In termini di tossicità non si sono inoltre verificati effetti collaterali cardiaci severi.

Adenoid cystic carcinoma of the breast. The double face of an exocrine gland carcinoma.

Adenoid cystic carcinoma (ACC) is the most common tumour of the minor salivary glands, but it also represents a rare type of breast cancer, accounting for 0.1– 1% of all breast tumours [1, 2]. ACC of the breast usually presents with a favorable prognosis due to its low incidence of lymph node and distant metastasis [1]. Management is currently similar to that of other breast cancer comprising mastectomy or breast conserving treatment with axillary dissection or sentinel node biopsy, radiotherapy and chemotherapy. We reviewed our experience with patients affected by ACC treated at our institute. From 1990–2007 we treated 13 women affected by ACC, all patients underwent to definitive quadrantectomy, 2 patients underwent sentinel lymphnode biopsy and 11 patients axillary lymph node dissection. Histology confirmed the presence of ACC in all the patients; however in 3 cases it was intermingled with ductal carcinoma. Rare are the cases of ACC intermingled with other types of breast cancer; in literature there are some case reports where ACC is mixed with other histology as small cell carcinoma [3] and spindle cell carcinoma [4]. The analysis showed negative margin with tumor at least 10 mm from the gross margin. Only 2 patients had positive lymph nodes with an N2a stage in both cases. The incidence of lymph node metastasis is very low; in literature axillary involvement appears in approximately 15% [5]. Sumpio et al. [6] showed in 120 cases from the literature, lymph node metastases in only 4 cases. Sentinel biopsy should be proposed in the presence of ACC of the breast, reserving the more invasive axillary dissection to individual cases. Estrogen and progesterone receptors were negative in 9 patients, while HER2 was positive in only 1 case. Very common is the triple negative status in this kind of tumor, e.g. Leeming et al. [7] reviewed 140 cases and found only one case positive ER. All the patients received adjuvant whole breast radiotherapy (range 50– 60 Gy) and 2 patients underwent adjuvant chemotherapy for positive lymph nodes; hormonal therapy was administered in 3 out of the 4 cases of positive receptors. At a median follow-up of 74 months after resection, 1 patient presented local relapse and 1 patient distant metastasis. The patient with local relapse was operated for a tumour of 4 cm, histology was positive for ACC and ductal carcinoma with positive hormonal receptors. Distant metastases occur most frequently in the lung, without sentinel lymph node involvement as in our patient. In our analysis none died from disease. In conclusion, primary treatment of ACC of the breast is surgical and quadrantectomy can be a valid approach if followed by radiation therapy on the whole breast [8]; unknown is the role of chemotherapy. It is important to recognize ACC of the breast as different entity from ACC of head and neck, the implications for management and outcome are significantly different but due to the rarity of the histology there are no standardized guidelines.