Giovanna Salerno

Squamous cell carcinoma antigen: prognostic significance and role in the monitoring of neoadjuvant chemotherapy response in cervical cancer.

PURPOSE The aim of the study was to investigate the role of squamous cell carcinoma antigen (SCC) in the management of patients with locally advanced cervical cancer treated by neoadjuvant chemotherapy and radical surgery. PATIENTS AND METHODS SCC assay was performed with a radioimmunoassay kit in a series of 102 patients with locally advanced cervical cancer. The values of 2.5, 5, and 7 ng/mL were used to define SCC antigen positivity. The chi 2 and Fishers exact test and the stepwise logistic regression were used to evaluate the distribution of marker values. Analysis of survival was performed using the Kaplan and Meier test and Cox multivariate regression analysis. RESULTS SCC levels were elevated in 65%, 45%, and 32% of patients with primary tumors for cutoff values of 2.5, 5, and 7 ng/mL, respectively. SCC pretreatment levels correlated with stage, tumor volume and lymph node status. In the multivariate analysis, SCC expression proved to be an independent predictor of response to neoadjuvant chemotherapy. SCC posttreatment levels were strongly related to chemotherapy response. Moreover, the overall correlation between the clinical course of the disease and the variation of SCC levels was 83%. In patients with squamous cell tumors, survival was significantly longer in SCC-negative cases compared with SCC-positive cases (P = .04). Moreover, in patients undergoing surgery after response to neoadjuvant chemotherapy, low SCC values were associated with better prognosis (P = .02). In the multivariate analysis, parametrial involvement and SCC status proved to retain an independent prognostic value. CONCLUSION Our data show that SCC assay may provide useful information to improve the prognostic characterization and disease monitoring of patients with locally advanced cervical cancer undergoing neoadjuvant chemotherapy.

Flap algorithm in vulvar reconstruction after radical, extensive vulvectomy

The objective of this study was to assess the reconstructive options after radical, extensive vulvectomy; relate them to tumor characteristics; and select a choice of flaps able to correct every remaining defect. This study is a retrospective review of a 4-year experience with 31 flaps in 20 consecutive vulvar reconstructions. Three of the 31 flaps presented nonsignificant delayed healing at their tips and 3 other flaps developed a major breakdown related to an infection or an error in flap planning. According to the authors, the size of the defect is the main issue that must be taken into consideration during the establishment of reconstructive needs. Closure of vulvar defects is preferably performed using fasciocutaneous flaps, which are very reliable flaps and can be raised with different techniques to meet different needs. A flap is then chosen with the fewest potential complications. An algorithm has been thus established: Small to medium-size defects are closed with island V-Y flaps, island gluteal fold flaps, or pedicled pudendal thigh flaps. Among them, the island V-Y flap is the workhorse flap for vulvar reconstruction because of its versatility, reliability, and technical simplicity compared with its very low complication rate. If the vulvar defect is large and/or reaches the vulva–crural fold, V-Y flaps are also preferred to close these large and posteriorly extended excisions. If the vulvar defect is very large, extending both anteriorly and posteriorly, the use of a distally based, vertically oriented rectus abdominis muscle flap is recommended. Using this algorithm, immediate vulvar reconstruction with pedicled local or regional flaps can be performed easily and reliably.

Autologous blood stem cell harvesting and transplantation in patients with advanced ovarian cancer

We investigated the feasibility of a programme of autologous blood stem cell (ABSC) harvesting and transplantation in 13 patients with advanced ovarian cancer, previously untreated by chemotherapy or radiotherapy and entering a phase II study of high‐dose cisplatin, etoposide and carboplatin with haematopoietic stem cell rescue. Prior to high‐dose treatment all patients underwent two courses of cisplatin and cyclophosphamide. An 8‐fold increase of the peripheral colony forming unit granulocytic‐macrophage (CFU‐GM) was observed during recovery from myelosuppression after the first chemotherapy course. The second course determined a 2·5‐fold increase of peripheral CFU‐GM. In 70% of enrolled patients (nine patients) we were able to perform ABSC harvesting by leukaphereses; in the apheresed patients we harvested an average of 20·8 × 104/kg CFU‐GM (range 10·9–37·0). Haematopoietic trilineage engraftment, established as the number of days necessary to reach white blood cells (WBC) >1·0 × 109/1, polymorphonuclear leucocytes (PMN) >0·5 × 109/1 and platelets (PLT) >50·109/1. occurred very promptly and was sustained in the same series after high‐dose cisplatin, carboplatin and etoposide, followed by autologous blood stem cell transplantation (ABSCT). In our experience we found a significant correlation (r = 0·77; P<0·05) between CFU‐GM infused dose and the engraftment speed of PMN. We conclude that the combination of cisplatin and cyclophosphamide is effective in mobilizing haematopoietic progenitors in the peripheral blood of patients with advanced ovarian cancer, previously untreated by chemora‐diotherapy. Moreover, ABSCT is capable of rapidly restoring the haematopoietic function after high‐dose treatment and for this reason it represents a particularly advisable therapeutic option for the treatment of solid tumours because these patients are commonly older than 50 and can be excluded from bone marrow transplantation.

The combination of erythropoietin and granulocyte colony-stimulating factor increases the rate of haemopoietic recovery with clinical benefit after peripheral blood progenitor cell transplantation

In order to investigate the effects of erythropoietin (EPO) plus granulocyte colony‐stimulating factor (G‐CSF) administration after peripheral blood progenitor cell transplantation (PBPCT) we performed a phase I/II study in patients with high‐risk cancer. 15 consecutive patients were treated with recombinant human G‐CSF (rhG‐CSF) at the dose of 5 μg/kg subcutaneously (s.c.) every 24 h until day +12 and with recombinant human EPO (rhEPO) at the dose of 150 IU/kg s.c. every 48 h until day +11 following PBPCT. Their haemopoietic recovery was compared to that obtained in eight historic control patients who did not receive any cytokines after PBPCT. No side‐effects were observed during EPO plus G‐CSF treatment and the treatment was not discontinued in any of the patients before completion of the treatment plan. The administration of EPO plus G‐CSF after PBPCT produced a significant increase in the rate of white blood cell (WBC) (P = 0.0005), polymorphonuclear leucocyte (PMN) (P = 0.0005) and platelet (PLT) (P = 0.0105) recovery compared to the control group. The acceleration in haemopoietic recovery observed in the EPO plus G‐CSF‐treated patients produced a significant reduction of the days with WBC < 1×109/l (P = 0.0009), PMN  < 0.2×109/l (P = 0.0030) and PMN < 0.5×109/l (P = 0.0006). EPO plus G‐CSF‐treated patients required a significantly lower number of single donor PLT transfusions (P = 0.0142) and did not experience neutropenic fever, but historic control patients experienced fever > 38°C for a median period of 4 d (0–12) with a median period of parenteral antibiotic administration of 7.5 d (0–17). The length of the hospital stay was significantly shorter in the study group than in the historic control group (P = 0.0264). In conclusion, we can confirm that EPO plus G‐CSF treatment is feasible and potentiates the haemopoietic recovery after PBPCT, thus simplifying the clinical management of cancer patients who undergo high‐dose chemotherapy.

The role of growth factor administration and T‐cell recovery after peripheral blood progenitor cell transplantation in the treatment of solid tumors: results from a randomized comparison of G–CSF and GM–CSF

BACKGROUND: Peripheral blood progenitor cell (PBPC) transplantation (PBPCT) combined with post‐PBPCT administration of myelopoietic growth factors is a valid therapeutic intervention to rapidly restore hematopoiesis after the delivery of intensive, myeloablative cancer chemotherapy. On the other hand, the best growth factor regimen to potentiate PBPC‐mediated immunohematopoietic recovery has yet to be determined.

161 O - Very high-dose chemotherapy (VHDCT) with ematologic support in previously untreated advanced ovarian cancer (OVCA): preliminary results of a phase I-II study

Two consecutive trials were conducted to evaluate a VHDCT programme with autologous bone marrow (ABM) or perlpheral stem cell (APSC) support in previously untreated OVCA patients (Pts) with macroscopic (0.5–2cm) residual tumor. Fifthy-one pts (median age 44; stage IIIC 78%) underwent: Induction chemotherapy (Indct) (2–4 cycles of a cisplatin and cyclophosphamide combination +/- G-CSF) with ABM and/or APSC hsrvestlng (H) foflowed by intensification (Int) CT (one course of a platinum, etoposide combination +/- L-PAM, +/-G-CSF&EPO) In the absence of clinical progression. 2nd-look laparotomy was performed in complete responders. 42 (82%) and 39 (76%) pts are evaluable for toxicity and pathological response (PR), respectively while 6 pts are still on treatment, 3 progressed when on treatment, 2 are awaiting 2nd look. One toxic death occurred due to systemic mycosis in a pt undergoing ABM transplantation (T). The number of leukaphereses required for adequate APSCH decreased after G-CSF Incorporation. Duration of BM aplasia progressively decressed lor pts receiving ABMT. APSCT and APSCT + G-cSF & EPO, respectively. 90% pR (CR 44%, PR 41% of which 36% microscopic) was revealed at 2nd-1ook. A median follow up of 28 (2–79) months has been reached from diagnosis. Only 2 of the 19 pathologically complete responders (6 with a > 5 year follow-up from 2nd-look) have so far relapsed without further therapy. Treatment proved to be feasible with acceptable toxicity when APSCT + G-CSF & EPO were used. The disease-free Interval would seem to be longer than expected in this pt subset. These data, if confirmed after a prolonged observation, warrants further investigation (in a randomized setting) on the possible therapeutic impact of this new approach on chemosensitive tumors.