Multimodality approach in extra cervical locally advanced cervical cancer: chemoradiation, surgery and intra-operative radiation therapy. A phase II trial.

BACKGROUND: The goal of this study was to determine the rational of radical surgery with intra-operative high-dose radiotherapy after chemoradiation (RT-CT) in extra cervical locally advanced cervical cancer (LACC) patients. METHODS: Between 2000 and 2007, 42 LACC (stage IIA bulky-IVA) patients were treated at the Gynecologic Oncology Unit of the C.R.O. of Aviano in a Phase II Clinical Trial. Radiotherapy was administered to the whole pelvic region (50.4 Gy in 28 fractions) in combination with cisplatin (60 mg/mq) plus 5FU (750 mg/mq for 4 days) on first and fifth week of RT. Radical surgery with Intra-Operative Radiation Therapy (IORT) was performed 6-8 weeks after the end of RT-CT treatment. RESULTS: After RT-CT, 35/42 patients (83%) underwent radical surgery and IORT treatment. At pathologic examination 8/35 (23%) patients showed complete response, while the rest (27/35) had residual disease either microscopic (17/27) or gross (10/27). The 5-year disease free survival (DFS) and the 5-year overall survival (OS) were 46% and 49% respectively. There were significant better DFS and OS when residual tumor was absent or limited to the cervix, respectively 78% versus 16% and 81% versus 20% (p < 0.001). All recurrences occurred within 24 months from treatment. CONCLUSIONS: RT-CT followed by surgery and IORT in LACC patients seems to be active in a subgroup of patients with pathological complete response to treatment or partial response with residual tumor limited to the cervix.

Phase II trial of docetaxel, cisplatin and fluorouracil followed by carboplatin and radiotherapy in locally advanced oesophageal cancer.

This study was performed to assess the efficacy and safety of docetaxel, cisplatin and fluorouracil combination in patients with unresectable locally advanced oesophageal squamous cell carcinoma. Treatment consisted of docetaxel 60 mg m(-2), cisplatin 75 mg m(-2) on day 1 and fluorouracil 750 mg m(-2) day(-1) on days 2-5, repeated every 3 weeks for three cycles, followed by carboplatin 100 mg m(-2) week(-1) for 5 weeks and concurrent radiotherapy (45 Gy in 25 fractions, 5 days week(-1)). After radiotherapy, eligible patients either underwent an oesophagectomy or received high dose rate endoluminal brachytherapy (HDR-EBT). Thirty-one out of 37 enrolled patients completed the planned chemotherapy and 30 completed chemoradiation. After completion of chemotherapy, 49% (95% CI: 32.2-66.2) had a clinical response. Twelve patients (32%) underwent a resection, which was radical in 60% (postoperative mortality: 0%). A pathological complete response was documented in four patients (11% of enrolled, 30% of resected). The median survival was 10.8 months (95% CI: 8.1-12.4), and the 1- and 2-year survival rates were 35.1 and 18.9%, respectively. Grade 3-4 toxicities were neutropoenia 32%, anaemia 11%, non-neutropoenic infections 18%, diarrhoea 6% and oesophagitis 5%. Nine patients (24%) developed a tracheo-oesophageal fistula during treatment. Even if the addition of docetaxel to cisplatin and 5-fluorouracil (5-FU) seems to be more active than the cisplatin and 5-FU combination, an incremental improvement in survival is not seen, and the toxicity observed in this study population is of concern. In order to improve the prognosis of these patients, new drugs, combinations and strategies with a better therapeutic index need to be identified.

Capecitabine in combination with preoperative radiation therapy in locally advanced, resectable, rectal cancer: a multicentric phase II study.

BACKGROUND: The aim of the study was to evaluate tolerance and efficacy of preoperative treatment with capecitabine in combination with radiation therapy (RT) in patients with locally advanced, resectable, rectal cancer. PATIENTS AND METHODS: Fifty-three patients with potentially resectable T3, N0-2 (87%) and T4, N0-2 (13%) rectal cancer were treated with capecitabine (825 mg/m2, twice daily for 7 days/week) and concomitant RT (50.4 Gy/28 fractions). Patients underwent surgery after 6-8 weeks followed, upon physician's indications, by 4-months adjuvant capecitabine. The primary end point was to determine the rate of pathologic complete response. Secondary end points were to assess the rate of clinical response and the safety profile. RESULTS: All patients but two completed the RT programme and 47 (89%) received 81%-100% of the capecitabine dose (100% of dose in 72% patients, 81%-95% in 17% patients and 48%-74% in 11% of patients). No patient had grade 4 toxicity. Grade 3 toxicity occurred in six patients (11%) and consisted mainly of leucopenia (4%) and hand-foot syndrome (4%). Mild or moderate toxicity was common and included leucopenia (72%), diarrhea (40%), proctitis (34%) and skin toxicity (20%). The overall clinical response rate was 58% and the downstaging rate was 57%, with a pathologic complete response rate of 24%. Among 34 patients with low-lying tumors (

Intraoperative radiation therapy for retroperitoneal soft tissue sarcomas.

Treatment of retroperitoneal soft tissue sarcomas is a difficult clinical problem. Despite the improvement in resection rates in the most recent surgical series, local control still remains the main problem because of the high incidence of local recurrences after surgery. Postoperative radiation therapy has not been always successful because of dose-tolerance of surrounding normal structures, which prevent the delivery of adequate doses of radiation. To overcome this limitations, new therapeutic approaches including external-beam radiation and intraoperative radiation therapy (IORT) have been evaluated at some Institutions. The results of IORT with or without external-beam radiation are reviewed and our experience with preoperative radiation and IORT is reported. As treatment of retroperitoneal sarcomas has evolved into combined modalities including preoperative radiation, maximum surgical resection and IORT, a possible improvement in local control rates has been achieved. However, locoregional failures and the incidence of distant metastases remain a challenge, emphasising the need for further improvement in local and distant treatment. The new phase II trial, activated within the Italian Sarcoma Group, with preoperative concurrent chemo-radiation therapy and IORT is presented.

Radiotherapy and continuous infusion 5-fluorouracil in patients with nonresectable pancreatic carcinoma.

PURPOSE: The current standard local treatment for nonresectable pancreatic carcinoma is radiotherapy (RT) with concurrent 5-fluorouracil (5-FU); however, the optimal schedule for 5-FU administration has not been fully established. In this study, we report on our experience with the combination of RT and continuous infusion 5-FU in a group of patients with locally nonresectable pancreatic carcinoma. METHODS AND MATERIALS: Forty-two patients with adenocarcinoma of the pancreas were enrolled in a prospective clinical trial. RT was delivered using a four-field technique to a total dose of 59.4 Gy in 33 fractions. 5-FU was given through a central venous catheter at a dose of 300 mg/m(2)/day, 7 d/wk, throughout the entire course of RT. RESULTS: All patients completed the RT as planned, and 33 (78%) completed the full regimen of chemotherapy. Ten patients (23%) had a partial response, and 32 (77%) had stable disease. Subjective response, defined as the disappearance of symptoms observed at diagnosis, was also evaluated. Two patients (6%) had a complete, and 24 (75%) a partial, remission of symptoms. The median time to progression was 6.2 months, and the median survival time was 9.1 months. CONCLUSIONS: In terms of local control, the results of our study, with RT and protracted 5-FU infusion, compare well with those of other studies using RT and bolus 5-FU. The control of distant metastatic disease remains an open issue. However, the palliation of symptoms achieved by our treatment schedule in patients with a very poor prognosis and severe symptoms may be regarded as a positive result.

Postoperative radiotherapy and surgery in stage I endometrial carcinoma: a 10-year experience.

BACKGROUND: Data from the literature show that the incidence of pelvic recurrences in poor prognosis endometrial carcinoma is significantly reduced by combined surgery and radiotherapy compared to surgery alone. METHODS: In this paper we analyze the results of the combined treatment surgery plus adjuvant Irradiation in patients with endometrial carcinoma with regard to survival, site of progression, and toxicity. The surgical treatment consisted of total abdominal hysterectomy and bilateral salpingo-oophorectomy. Pelvic and para-aortic node dissection was performed. RESULTS: The overall 5-year survival was 88%. Three patients had local failure. Ten patients with local control of disease had distant metastases and 2 had local and distant recurrences. CONCLUSIONS: Our experience confirms the data of the literature. Postoperative irradiation is a safe and well tolerated treatment which can achieve good local control in high-risk stage I endometrial carcinoma. The control of distant metastases remains an open issue.

Temporomandibular joint metastasis from rectal carcinoma: CT findings before and after radiotherapy. A case report.

Metastatic disease to the masticator space and to the jaws is a rare event. About a dozen cases are reported in the current literature. We describe the imaging findings of a rectal adenocarcinoma metastatic to the temporomandibular joint before and after radiotherapy.

Solitary thyroid metastasis from a renal cell carcinoma diagnosed and treated 12 years before: a case report.

The authors report a case of a solitary thyroid metastasis in a 62-year-old woman. The clinical history of the patient and the histologic findings are consistent with a renal origin of the tumor.

Endometrial stage I carcinoma treated with surgery and adjuvant irradiation: a retrospective analysis.

AIMS AND BACKGROUND: Data from the literature show that the incidence of pelvic recurrences in poor prognosis endometrial carcinoma is significantly reduced by combined surgery and radiotherapy compared to surgery alone. METHODS: In this paper we analyze the results of the combined treatment surgery and adjuvant irradiation in patients with endometrial carcinoma with regard to survival, site of progression, and toxicity. The surgical treatment consisted of total abdominal hysterectomy and bilateral salpingo-oophorectomy in 40 patients. Pelvic and para-aortic node dissection was performed in 19 patients and lymph node sampling in 5. RESULTS: Overall 5-year survival was 85%. One patient had local failure, and 5 patients with local control of disease had distant metastases. Toxicity was mild and transient. CONCLUSIONS: Our experience confirms the data of the literature. Postoperative irradiation is a safe and well-tolerated treatment that can achieve a good local control in high risk, stage I, endometrial carcinoma. The control of distant metastases remains an open question.

[Combined surgical and radiotherapy treatment in endometrial cancer]. / Il trattamento combinato chirurgico e radioterapico del cancro dell'endometrio.

Early stage endometrial carcinoma is usually treated by surgery and radiotherapy if there is a substantial risk of recurrence. The aim of this study was to evaluate early and late toxicity, to determine the sites of recurrence and the prognostic factors which were statistically correlated with survival in patients who were treated with surgery plus external beam radiotherapy. MATERIALS AND METHODS. We have carried out a retrospective analysis of the records of 87 patients treated with hysterectomy plus external beam pelvic radiotherapy (50 Gy/28 Fractions), at the Radiotherapy Division of the CRO Aviano PN Italy, between 1985 and 1990. The median length of follow-up was 32.42 months. RESULTS. The treatment was well tolerated. The median time to recurrence was 6.56 months. There were 4.7% local, 5.8% distant and 3.5% local plus distant recurrences. As of May 1993 83.2% of the patients were still alive. All deaths occurred within two years from the beginning of treatment. The prognostic factors which were significantly correlated with survival were the stage of the disease (p = 0.0479), depth of myometrial invasion (p = 0.0429), age greater than 64 years (p = 0.0357) and performance status < = 80 at diagnosis (p = 0.0002). CONCLUSIONS. Our study confirms that post operative external beam pelvic RT is well tolerated and effective in achieving a good locoregional control. All the factors investigated were prognostic for survival, except histological grade, lymph node involvement and RT dose.

Radiation therapy and conservative surgery for soft tissue sarcomas of the extremities, torso and head and neck.

Between May 1985 and July 1990, 45 patients (pts.) with primary (39) or recurrent (6) soft tissue sarcomas of the extremities (82%), torso (11%) and head and neck (7%) were treated with radiation therapy and conservative surgery. Seven pts. not amenable to conservative surgery underwent preoperative radiation therapy whereas 38 pts. underwent local excision and post-operative radiation therapy. Out of the 38 pts. managed by postoperative radiation, 24 (63%) showed negative surgical margins and 14 (37%) positive margins, their tumor being adjacent to vital structures. Preoperative radiation allowed conservative surgery in all 7 pts. with initially inoperable tumor; surgical margins were negative in 5 and positive in 2 pts. Twenty-six pts. (58%) had tumor greater than or equal to 5 cm (5-24) and 19 (42%) less than 5 cm (2.5-4.5) in diameter. High grade tumors (G2-G3) were reported in 41 pts. (90%). In pts. treated postoperatively the radiation dose was 64-66 Gy/32-33 fractions and the pts. treated preoperatively received a dose of 50 Gy/25 fractions. Median follow-up was 33 months and all pts. had a minimum follow-up of 12 months (12-72). Three pts. (6.5%) had local failure and 9 (20%) developed distant metastases with local tumor control. All distant metastases occurred in AJC stage IIIB, 9/18 (50%), with an increased frequency by tumor size. Overall local control and disease free survival rates at 5 years (product-limit method) were 93% and 73%, respectively. An evident decrease in disease-free survival rate (33%) was noted for stage IIIB pts.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of timing of vincristine administration during a course of fractionated radiotherapy in a mouse carcinoma.

It has been previously shown that the uptake of 3H-vincristine by the NT carcinoma tumour in CBA mice can vary by a factor of 3 during a course of fractionated radiotherapy (2 Gy day-1, 5 day week-1, for 5 weeks). Here the effect of therapeutic doses of vincristine given at times of either maximum or minimum uptake has been investigated. The results show that whereas vincristine alone has a dose-related effect on this tumour, when given in combination with fractionated radiation it is only effective if administered during the first few fractions. It does not seem to matter whether it is given at times of maximum or minimum uptake. It is concluded that vincristine either exacerbates the radiation-induced vascular damage so that drug extravasation is reduced or that it causes a shift in the time of appearance of the peaks and troughs of uptake. The possibility that radiation-induced resistance to vincristine may have played a part in the results is also discussed.

Radiation therapy combined with chemotherapy for inoperable pancreatic carcinoma.

From March 1985 to July 1989, 22 patients with unresectable pancreatic adenocarcinoma entered the study to receive external beam irradiation with chemotherapy. Radiation therapy consisted of 60 Gy in 3 courses (20 Gy each course) delivered over a period of 2 weeks, with a 2-week rest between the courses. Chemotherapy consisted of 5 fluorouracil, 500 mg/m2, plus cisplatinum, 20 mg/m2, administered on days 1, 2 and 3 of each radiation therapy course. Of the 22 evaluable patients, 10 were males and 12 females; their median age was 63 years (range, 32-77), and their median performance status was 80 (range, 60-90). After treatment, 12 partial remissions and 6 no changes were reported. In 4 cases, abdominal progression of disease during treatment required interruption of the therapy program. At the start of treatment, abdominal pain was the most important symptom in 17 patients; improvement of abdominal pain was observed in 10 cases (76%) after treatment and lasted for a median of 5 months. Median survival time was 7.5 months, and time to progression was 6.2 months. Median follow-up was 7 months (range, 14 days -38). In 2 cases, persistent hematologic toxicity did not permit completion of therapy, and in another 3 cases grade II hematologic toxicity required a 2-week rest period over the normal split-course program. In another 4 cases, grade I hematologic toxicity did not require any delay in the therapy program. Our results are comparable with those achieved in other major studies and are acceptable in terms of survival time, palliation of symptoms and toxicity. In our experience, the combination of radiotherapy plus 5-fluorouracil and cisplatinum does not seem to offer any advantage over the combination of radiation therapy and 5-fluorouracil.

Postoperative radiotherapy in locally advanced head and neck cancer.

This retrospective study was conducted on 255 consecutive patients with locally advanced squamous-cell carcinoma of the oral cavity, oropharynx, larynx or hypopharynx, treated at the Radiotherapy Department of Pordenone General Hospital between January 1975 and December 1985. All patients underwent radical surgery followed, after an interval ranging from 10 days to 2.9 months, by radiotherapy given either through a 6 MeV linear accelerator or a cobalt-60 unit. Field extension and dose delivered were comparable in relation to stage and involvement of the surgical resection margins. The aims of the study were to evaluate the survival rate and to analyze the clinical parameters which can influence the disease-free survival. The adjusted overall 5-year survival rate was 71%; stage, performance status at diagnosis, and site of the primary tumor were significant factors in determining patient prognosis, whereas infiltration of resection margins was not significant in determining loco-regional control of disease. Seventy-five patients relapsed and 67 died of cancer-related diseases whereas death in 52 patients was not related to the head and neck cancer. The combined modality treatment consisting of surgery followed by radiotherapy was well tolerated and proved to be effective in the treatment of locally advanced head and neck tumors.

Chemotherapy of advanced head and neck squamous carcinoma with cisplatin, fluorouracil and bleomycin administered in an outpatient schedule.

From May 1983 to September 1984, 48 consecutive patients with locally advanced, recurrent and/or metastatic head and neck squamous carcinoma were treated with cisplatin 60 mg/m2 i.v. on day 1, fluorouracil 10 mg/kg i.v. push from day 1 to day 4 and bleomycin 10 mg/m2 i.v. from day 1 to day 4, every 3 weeks. In the 44 evaluable patients complete remission was observed in 4, partial remission in 9, stable disease in 19, and progression in 12, for a 29.5% response rate. When the analysis was limited to the 21 patients with PS greater than 70 and no previous chemotherapy or radiotherapy, the response rate was 48%. Toxicity was acceptable, and no treatment related deaths occurred. Overall median survival (all eligible patients) was 7 months. Although further studies with this combination in poor risk patients (previously treated or with PS less than 70) do not appear to be indicated, a more accurate assessment in good risk patients might be warranted.