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G Sanguineti

Publications and source records attributed to G Sanguineti.

52 records · Page 3Linked to original sources
PubMedDate not supplied

Cell kinetics analysis in patients affected by squamous cell carcinoma of the head and neck treated with primary surgery and adjuvant radiotherapy.

BACKGROUND: The increasing complexity of management strategies for patients with head and neck squamous cell carcinoma (HN-SCC) calls for the investigation of new objective prognostic parameters to subdivide patients according to the tumor's biological aggressiveness. METHODS: We evaluated in 35 HN-SCC patients the pretreatment cell kinetics parameters and DNA ploidy after in vivo infusion of bromodeoxyuridine and flow cytometric analysis. Patients were treated with radical surgery followed by conventional radiation therapy. Locoregional control data are available for follow-up times above five years. RESULTS: We found that the likelihood of locoregional control for patients with rapidly proliferating HN-SCC characterized by a short potential doubling time (Tpot <5 days) was significantly smaller than for HN-SCC patients with slow tumor proliferation (Tpot >5 days). Moreover, when patients were stratified according to DNA ploidy and Tpot value, we found that the locoregional failure rate for rapidly proliferating tumors was significantly higher for diploid HN-SCCs than for aneuploid HN-SCCs. CONCLUSION: The present data suggest that patients with resectable HN-SCC characterized by fast growth might have a worse prognosis after surgery and adjuvant conventional radiotherapy and might benefit from more aggressive radiotherapeutic modalities.

Adult↗
PubMedDate not supplied

Lack of a time-factor in alternating chemoradiotherapy for advanced head and neck squamous cell carcinoma.

PURPOSE: To assess wheiher a radiotherapy time factor exists also for patients affected by head and neck squamous cell carcinoma and receiving combined chemoradiotherapy. METHODS AND MATERIALS: From 1989 to 1997, of 121 patients affected by stage III or IV head and neck squamous cell carcinoma who underwent alternating chemotherapy and radiotherapy according to the Merlano regimen at our institution, 59 were selected for time factor analysis. Until 1995, if chemotherapy had to be delayed because of bone marrow toxicity, radiotherapy was also delayed accordingly. Since January 1996 in order to avoid treatment-free gaps, radiotherapy was delivered continuously until it was possible to resume chemotherapy. Potential predictive factors of local-regional control were included in univariate and multivariate models. The median follow-up is 26 months (5-121 months). RESULTS: As a result of change in treatment policy, mean radiotherapy duration was shorter for 25 patients treated after 1995 (group A, 8.4 weeks) than for those treated during 1995 or before (group B, 9.4 weeks) (t test, P = 0.0012). In contrast, as expected, mean chemotherapy duration remained relatively unchanged through the years (10.9 vs 10.7 weeks for groups B and A, respectively, t test, P = 0.77). At 2 years, the actuarial local-regional control rate was 53 +/- 7% for the whole population. The estimated rates of local-regional control at 2 years were 49 +/- 10% and 56 +/- 9% for patients belonging to groups A and B, respectively. At univariate and multivariate analyses, treatment group was not predictive of local-regional control. CONCLUSIONS: Our attempt to prospectively limit radiotherapy overall treatment time failed to improve outcome. The data, although obtained on a relatively limited number of patients, suggest that tumor cell repopulation during radiotherapy may not be clinically relevant when chemotherapy is part of the treatment for advanced head and neck squamous cell carcinoma.

Actuarial Analysis↗
PubMedDate not supplied

Biological predictors of response to radiotherapy in head and neck cancer: recent advances and emerging perspectives.

The study of new biological parameters has received considerable attention in radiotherapy during the last decade due to their potential value in predicting treatment response in squamous cell carcinoma of the head and neck (SCC-HN) and the foreseen possibility of selecting altered fractionation radiotherapy for the individual patient. Although there are established clinical parameters in SCC-HN patients that relate to radiation response (extent of disease, hemoglobin level), recent advances with direct measurement of tumor oxygenation, inherent radiosensitivity and proliferation rate have increased the promise of individualization of treatment strategy according to these radiobiologically based parameters. Molecular research has now identified a host of new biological parameters with potential predictive utility; oncogenes, tumor suppressor genes, cell-cycle control genes, apoptosis genes and angiogenesis genes have been extensively studied and correlated with radiation response. Moreover, study of the epidermal growth factor receptor signal-transduction system as a possible response modulator has recently fostered molecular strategies which employ blockade of the receptor to down-regulate tumor growth. This article briefly reviews and analyzes the main controversial issues and drawbacks that hinder the general use of biological parameters for predicting tumor response to radiotherapy. It highlights the future perspectives of radiotherapy predictive assay research and the need to shift from single-parameter analysis to multiparametric studies which take into account several potential predictors that together are involved in different biological and clinical pathways.

Apoptosis↗
PubMedDate not supplied

Biological and clinical implications for multimodality treatment in patients affected by squamous cell carcinoma of the head and neck.

AIMS AND BACKGROUND: Several strategies combining radiotherapy and chemotherapy have been developed for the cure of squamous cell carcinoma of the head and neck (SCC-HN) in an attempt to improve loco-regional control and survival. This overview aims to summarize clinical results of reported randomized trials and to discuss the biological mechanisms underlying the interactive and non-interactive processes promoted when chemotherapy is added to radiotherapy. METHODS: The clinical goals of combined modality therapy and exploitable associations of chemotherapy and radiotherapy that may lead to a therapeutic gain in comparison with radiotherapy alone are reported and reviewed. Clinical applications of the four main ways of combining chemotherapy with radiotherapy (neoadjuvant, concomitant, alternating and adjuvant) are briefly re-analyzed and discussed. RESULTS AND CONCLUSIONS: Published evidence suggests that induction chemotherapy (neo-adjuvant) should not be routinely recommended; however, induction chemotherapy increases the likelihood of larynx preservation in patients with laryngeal and hypopharyngeal cancer and should be offered as a treatment option as an alternative to surgery. Positive results of several randomized studies and a recent meta-analysis show that concomitant use of chemotherapy and radiotherapy in unresectable SCC-HN is beneficial and should be considered as a potential standard treatment. A complementary biological staging of SCC-HN, by evaluating new predictive factors of tumor response, is presently under investigation to better interpret clinical randomized trials exploring chemo-radiotherapy.

Carcinoma, Squamous Cell↗
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Treatment of nasopharyngeal carcinoma: state of the art and new perspectives (review).

The role of radiotherapy and the current strategies to improve outcome in nasopharyngeal carcinoma are reviewed. Emphasis is on the factors, which may provide a more accurate selection of patients for more aggressive treatments. Clinical data suggest that local failure and distant metastases are separate events. Thus, strategies to optimize one of them are not expected to impact significantly on the other. Patients with advanced T stage disease, cranial nerve palsy, bulky primary lesions and well differentiated tumors may benefit from more local aggressive treatment. These include higher dose radiotherapy throughout conformal 3D radiotherapy and brachytherapy. Altered fractionation schedules and concomitant chemotherapy may also enhance the results obtained by conventional external beam radiotherapy. Patients with advanced neck disease and/or low neck nodes are candidates for additional systemic treatments as well. The role of technical innovations in radiotherapy delivery and that of altered fractionation schedules are unknown, even if results from phase II studies are promising. Regarding chemotherapy, have shown some impact of chemotherapy on outcome. However, additional testing is needed in order to improve the therapeutic index and validate its rationale.

Antineoplastic Agents↗
PubMedDate not supplied

On the delineation of the gross tumor volume and clinical target volume for head and neck squamous cell carcinomas.

Gross tumor volume (GTV) and clinical target volume (CTV) delineation on planning computed tomography (pICT) for head and neck squamous cell carcinomas can be troublesome. We highlight the factors which can be crucial for the radiation oncologist in delineating GTV and CTV on pICT and provide some pratical solutions. Regarding GTV, uncertainties are correlated with transfer of information collected by physical examination and diagnostic radiology to pICT. Moreover, reproducibility of delineation can also be highly variable, particularly when diagnostic imaging quality and pICT quality are poor. Once the prescription has been made, clinical target volume identification on pICT is rarely straightforward. Whereas there are some data about the location of major lymph node stations of the neck, there are no reported guidelines on how to draw subclinical extention of primary head and neck tumors on pICT. Such volumes can be derived from those currently included in simulator films or from those addressed by the surgeon. Some examples are provided. A particular situation is represented by the adjuvant setting, when the primary tumor is removed (by surgery) or reduced (by chemotherapy). In conclusion, this paper shows some major problems associated with identification of GTV and CTV on pICT. Apart from selected cases, the use of pICT for target volume delineation (and thus for field shaping) for head and neck squamous cell carcinoma is still to be considered investigational.

Carcinoma, Squamous Cell↗
PubMedDate not supplied

[Cell kinetic analysis and treatment planning in epidermoid tumors of the head and neck].

Cell kinetic parameters were evaluated using the method based on in vivo incorporation of Bromodeoxyuridine (BrdU) and flow cytometric (FCM) analysis in 30 human epidermoid head and neck tumors from oropharynx, oral cavity, rhinopharynx, larynx and lips. BrdU was injected four/six hours before the obtainment of multiple bioptic samples from the tumor tissues. The flow cytometric method was carried out on 70% ethanol fixed cell suspensions based on established protocol for the simultaneous evaluation of DNA content and BrdU uptake using anti-BrdU monoclonal antibodies. We have evaluated the following FCM parameters: DNA ploidy, the degree of DNA aneuploidy (DNA index), Labelling Index (LI), duration of s-phase (Ts) and tumor potential doubling time (Tpot). LI values ranged from 1.5 to 20% with a median value of 10%. The median LI of DNA diploid tumors was 5.4% compared to 14% in DNA aneuploid tumors. Ts values ranged from 8 to 11, the median value being 10 hours. Tpot values ranged from 2 days to 16 days, the median Tpot being 5 days. The large heterogeneity of all these parameters indicates that these tumors may have a different degree of biologic aggressiveness (9). Tpot values did not correlate with DNA ploidy nor with lymph node metastasis status. Tpot values did not correlate in a statistically significant manner with degree of differentiation although shorter Tpot were more frequently observed in moderate or poorly differentiated tumors. Our study shows that the FCM-BrdU technique in vivo is feasible in a clinical setting to evaluate the proliferative behaviour of head and neck tumors, before any specific therapeutic decision is taken after surgery is performed. It is likely that tumors with more aggressive biological behavior, as indicated by LI > 15%, DNA aneuploidy and Tpot < 5 days, may benefit from more aggressive therapies such as accelerated regimeus of radiotherapy and/or other multimodal therapies in respect to tumors with slow growth rate (LI < 15%), DNA diploidy and Tpot > 5 days. So far, however, it still remains to be demonstrated from randomized clinical trials if the knowledge of such individualized cell Kinetic parameters really can help to choose the most effective therapy for every individual patient.

Bromodeoxyuridine↗
PubMedDate not supplied

Mitotic activity of schwannomas.

A significant (p less than 0.01) difference in the mitotic index between 31 benign and 4 malignant schwannomas is reported. An increased mitotic activity has been related to malignancy in previous works, although no statistical studies have been carried out on its diagnostic value. Our results suggest that the mitotic index should be considered an effective, convenient feature of distinction in doubtful instances, especially as no other trait of malignancy can be similarly measured.

Adult↗
PubMedDate not supplied

Correlation between immunohistochemical patterns and serum levels of PSA and PSAP in prostatic pathology: evaluation of 198 prostatic fine needle biopsies.

PSA and PSAP were examined in 198 prostatic biopsies and correlated with PSA and PSAP serum levels evaluated before biopsies. In every type of lesion there was no relation between PSA or PSAP serum levels and their expression in biopsy specimens. PSA and PSAP staining was similar in both cancer and benign hyperplasia and lower in dysplasia, atrophy and prostatitis; while serum levels were higher in adenocarcinomas than in other lesions. A significant difference of PSAP serum levels was noted in different Gleason's grading of neoplasia, found neither with PSA serum levels/nor with PSA and PSAP tissue staining.

Acid Phosphatase↗
PubMedDate not supplied

[The prognostic role of the parameters of cellular kinetics in head and neck tumors treated solely by radiotherapy].

Cell cycle and cell population characteristics, as obtained for head and neck cancers by flow-cytometry analysis of a single tumor sample, after in vivo bromodeoxyuridine (Burd) infusion, were proposed for their prognostic value and for their potentials for radiotherapy planning (conventional vs accelerated) and monitoring. DNA ploidy, the S phase fraction labeling index (LI), and duration (Ts) as well as cell population potential doubling time (Tpot) were measured in 42 head and neck squamous cell carcinoma patients and analyzed along with histopathological and clinical data. Twenty-seven patients received standard radiotherapy (70 Gy/35 fractions/7 weeks) whereas 15 patients were treated with the concomitant boost technique (75 Gy/40 fr/6 weeks). The univariate analysis of 31 patients, for whom all the cell kinetic parameters were available, indicated that local control probability was strongly affected by lymph node status (p = 0.05) and by potential doubling time (p = 0.04). Patients having tumor Tpot < 5 days had markedly lower two-year local control rate (13%) than patients with Tpot > 5 days (68%). Furthermore, tumors with Tpot < or = 5 days exhibited a trend toward better local control after concomitant boost regimen compared with the patients treated with standard regimen (p = 0.06). These preliminary results point out that Tpot could play a role as additional prognostic factor influencing disease outcome in head and neck carcinomas treated by radiotherapy. In patients with fast growth-rate tumors (Tpot < or = 5 days) a more aggressive radiotherapy combination or chemo-radiotherapy should be suggested.

Actuarial Analysis↗
PubMedDate not supplied

Concomitant administration of two standard regimens of chemotherapy and radiotherapy in advanced squamous carcinoma of the head and neck: a feasibility study.

BACKGROUND: In advanced squamous cell carcinoma of the head and neck, the superiority of a chemo-radiotherapy combination over radiotherapy alone has been strongly suggested. However, the best modality to combine the two treatments has still to be determinated. A pilot study was designed, testing a combination of two standard chemo- and radiotherapy regimens concomitantly administered. MATERIALS AND METHODS: 26 patients, with unresectable squamous cell carcinoma of the head and neck, were treated with three cycles of chemotherapy (cisplatin 20 mg/m2/day and fluorouracil 200 mg/m2/day as an intravenous bolus, for 5 consecutive days, every 21) simultaneously delivered with radiation (66-70 Gy/33-35 fractions/7 weeks). In order to reduce the mucoseal toxicity. observed in the first 15 patients, 1 week of pause was inserted after the third week of treatment in the subsequent 11 patients. RESULTS: Grade III-IV mucositis was detected in 40% of patients treated without pause after the third week of treatment and in 9% of those treated with. Complete responses were obtained in 13/26 patients (50%) and partial responses in 8/26 (31%). 1 stable disease, 3 early deaths (1 because of toxicity) and 1 lost before being evaluated were considered as treatment failures (19%). CONCLUSIONS: This concomitant chemo-radiotherapy approach showed a good antitumour activity but mucoseal toxicity is too high if no pause is planned during the treatment.

Adult↗
PubMedDate not supplied

In vivo cell kinetics in elderly patients affected by squamous cell carcinoma of the head and neck.

The purpose of the study was to determine whether pretreatment tumor cell kinetics can predict local control in elderly patients affected by squamous cell carcinoma of the head and neck (SCC-HN) and help guide different therapeutic modalities. Over a 6-year period, 52 patients with stage II to IV SCC-HN and aged more than 70 years were given an infusion of bromodeoxyuridine (BrdUrd) 6 hours prior to tumor biopsy sampling. The simultaneous labeling S phase fraction (LI) and duration (Ts) as well as potential doubling time (Tpot) were measured with flow cytometric analysis of BrdUrd and DNA content. Patients were then treated as follows: 14 with conventional radiotherapy; 13 with partly accelerated radiotherapy; 11 with chemoradiotherapy; 14 with surgery plus adjuvant radiotherapy. Univariate analysis showed that, independently of treatment type, patients with fast growing SCCs-HN characterized by Tpot value < or = 5 days had a lower three-year local control than patients with slow growing tumors with Tpot value > 5 days. Our results also demonstrated that surgery or chemoradiotherapy were effective treatments for fast growing tumors. Radiotherapy alone, instead, was more effective for slow growing tumors. Our data suggest that in vivo cell kinetics may play a role as additional prognostic factor for elderly patients with SCC-HN and predict the outcome of different treatments.

Aged↗
PubMedDate not supplied

Predictive factors for outcome in invasive bladder cancer treated with alternating chemoradiotherapy.

PURPOSE: In order to select patients properly for a bladder preservation program, this retrospective study aimed to evaluate the predictive role of pretreatment- and treatment-related factors in a group of patients with invasive bladder cancer treated with alternating chemoradiotherapy at a single institution. METHODS AND MATERIALS: From 1986 to 1994, 72 patients with invasive bladder cancer, stages T1 poorly differentiated or T2-4M0 refusing surgery or not eligible for surgery, were treated with alternating chemoradiotherapy. Each patient had a pretreatment cystoscopy with an attempted complete transurethral resection of the bladder tumor (TURB). The treatment schedule consisted of chemotherapy (cisplatin, 5-fluorouracil, or methotrexate) alternated with radiotherapy. Over the years, the treatment schedule was modified with respect to the total number of chemotherapy cycles, the type of chemotherapy drugs, the dose per fraction and total dose of radiation therapy, and the presence of a planned treatment gap at midtreatment. Treatments were aligned in order of their received average relative dose intensities of both chemotherapy (ARDICT) and radiotherapy (RDIRT). RESULTS: Twenty-two patients (76%) developed infiltrative bladder recurrences for an estimated 5-year pelvic control rate of 68% +/- 6%; 5-year actuarial survival with intact bladder is 40% +/- 6%. Obstructive uropathy at diagnosis, residual disease after TURB, and ARDICT value equal or below the median were independent predictive factors for pelvic failure, with hazard ratios of 2.87 (95% confidence interval [CI], 1.16-7.04), 8.13 (95% CI, 2.74-24.1), and 3.36 (95% CI, 1.29-8.74), respectively. A more detailed model including interactions among these factors showed that the negative prognostic effect of obstructive uropathy at diagnosis was not modified by ARDICT or TURB resection; on the contrary, the risk of local failure for patients with incomplete TURB was markedly affected by different levels of ARDICT. Also, a trend toward a better local outcome was observed for patients with RDIRT above the median. Hydronephrosis and incomplete TURB were also independent predictors of distant metastases and overall survival, but no effect was found for ARDICT on these endpoints. DISCUSSION: As a result of this analysis we believe that (1) patients with obstructive uropathy should not be offered a bladder-sparing approach, (2) gross total TURB of the primary tumor should be maximized, (3) prompt surgery should be considered for patients with incomplete TURB who are not compliant with the combined-modality treatment, and (4) the intrinsic value of dose intensity of both chemotherapy and radiotherapy should be confirmed in a prospective, controlled study.

Adult↗