Salvage Low Dose Rate Brachytherapy For Recurrent Prostate Cancer After External Beam Radiotherapy: Results From A Single Institution With Focus On Toxicity And Functional Outcomes.

BACKGROUND/AIM: Low dose rate brachytherapy has been used as salvage therapy for locally recurrent prostate cancer (PC) after primary external beam radiation therapy (EBRT), along with surgery and cryotherapy. All these techniques, in particular, when applied to the whole gland, involve a relatively high risk of toxicity and may worsen the patient's quality of life. Our aim is to evaluate the results of whole-gland salvage brachytherapy (SBT) after primary EBRT in terms of toxicity, functional outcomes, and efficacy. MATERIALS AND METHODS: We retrospectively reviewed clinical data on 19 patients consecutively treated with SBT at our institution between June 2012 and November 2015. Local recurrences were identified with 11C-choline positron emission tomography/computed tomography and pelvic magnetic resonance imaging after biochemical recurrence according to Phoenix criteria (prostate-specific antigen nadir + 2). Low dose rate brachytherapy was performed by 125I permanent seeds implantation to the whole prostate gland, with a prescription dose of 130 Gy. At the time of SBT, only 2 patients were receiving androgen deprivation therapy. Acute and late toxicities were recorded using the CTCAE 4.0 scoring system. Quality of life was assessed using IPSS (International Prostate Symptoms Score) and IIEF (International Index of Erectile Function) questionnaires at baseline and 6, 12, and 24 months after SBT, and the respective mean values were compared using Student t test. Biochemical relapse-free survival (BRFS) was also calculated. RESULTS: Median follow-up after SBT was 24 months. Of 19 patients, 2 patients experienced a G3 cystitis (10.2%) and 1 patient experienced a G4 proctitis (5.3%), respectively. Mean pre-SBT IPSS scores and 6, 12, and 24 months after SBT were 5.84, 10.22, 15.72, and 8.10, respectively. Mean pre-SBT IIEF scores and 6, 12, and 24 months after SBT were 8.42, 3.55, 7.89, and 6.40, respectively. At the time of analysis, only 2 patients showed a biochemical relapse (3-year BRFS 85.2%). The Student t test demonstrated a worsening of functional outcome 6 months and 1 year after treatment but a subsequent improvement 2 years after SBT. CONCLUSIONS: Salvage brachytherapy for recurrent PC after primary EBRT seems to be a feasible treatment for selected patients. Our series revealed a severe toxicity peak 6 months and 1 year after local re-treatment and then they decrease. Early BRFS rates are good. However, these are very preliminary results so further patient accrual, long-term follow-up, and prospective trials are needed in the future.

Survival and toxicity of radical radiotherapy (with or without brachytherapy) for FIGO stage I and II cervical cancer: a mono-institutional analysis.

PURPOSE OF INVESTIGATION: To add to the existing outcome data regarding radical radiotherapy (RT) for FIGO Stage I and II cervical cancer in a mono-institutional series and to evaluate the cost-benefit ratio of the addition of brachytherapy (BRA) to external-beam radiotherapy (EBRT). MATERIALS AND METHODS: The authors report on 240 patients (pts) with FIGO Stage I and II cervical cancer, consecutively treated with radical RT from 1990 through 2009 at the Istituto del Radio "O. Alberti" (EBRT alone, 32, EBRT and BRA, 189, BRA alone, 19). BRA was delivered with low dose rate (LDR, 133.64%) until 2003 and then with high dose rate (HDR, 75.36%). RT was associated with concomitant chemotherapy (CHT), mainly weekly cisplatin 40 mg/m2, in 87 pts, mostly after 2000. The Chi-square test was used to compare the different variables, the Log-Rank test to compare the actuarial survival values, and the Cox-model for the multivariate analysis. RESULTS: Five-year actuarial overall survival (OS) equalled 65%, disease specific survival (DSS) 77%. Regardless of disease stage, better DSS was evident in pts treated with EBRT and BRA compared with those treated with EBRT alone (82% and 58% respectively, p = 0.005); pts treated with concomitant CHT (dose intensity > or = 50%) and higher RT doses (RT cumulative EQD2 > or = 75 Gy) obtained better DSS. Complete response (CR) rate approached 88.4% (206/233 evaluable pts) and more than half of the subsequent failures (21/36) were in distant sites. Older patients and those given BRA had better OS and DSS, while BRA dose rate did not result related with these outcomes. Chronic G3/G4 toxicity involved more frequently the intestinal/rectal tract than other organs at risk. Rectal and vaginal serious chronic sequelae developed mainly in pts treated with EBRT and BRA and suggest the need for more advanced treatment techniques. CONCLUSIONS: the present mono-institutional analysis confirms the efficacy of radical RT for the treatment of cervical cancer and provides support to the role of BRA to obtain better outcomes. An effort to reduce long-term toxicity of the treatment is needed.

Postmastectomy radiotherapy and concomitant adjuvant chemotherapy versus adjuvant chemotherapy alone in premenopausal breast cancer patients with positive axillary nodes.

AIMS: To evaluate the efficacy of postmastectomy radiotherapy (RT) combined with adjuvant chemotherapy compared to adjuvant chemotherapy alone as regards overall survival (OS), overall disease-free survival (ODFS), local disease-free survival (LDFS) and distant disease-free survival (DDFS). METHODS: We reviewed retrospectively two non-randomized groups of premenopausal high-risk breast cancer patients treated from 1985 to 1990 in the following Institutions: Department of Radiation Oncology of Brescia University, "Istituto del Radio O. Alberti" (IRA), and Department of Oncology of Brescia Hospital "Beretta Foundation" (BF). A total of 163 patients was found to satisfy the criteria of the current analysis: 81 patients received adjuvant chemotherapy alone [6 cycles CMF(1-8)] at BF and 82 patients received postoperative radiotherapy and chemotherapy [8 cycles CMF(1-21)] at IRA. A modified CMF schedule was chosen at IRA to avoid the feared increase in toxicity due to the association with RT. Primary surgical treatment was modified radical mastectomy with axillary node dissection in both cases. RESULTS: A statistically significant improvement in OS was found in systemic adjuvant therapy patients compared to those also given RT (77.6% vs 59%; P = 0.0025). No statistically significant improvement in ODFS was found in the CMF(1-8) arm compared to the RT and CMF(1-21) stm: 51.6% vs 43.6%; P = 0.46. A statistically significant improvement in LDFS at 5 years was found in irradiated patients (89.3% vs 76.2%; P <0.05). The DDFS was also improved, although without evidence of statistical significance, in the CMF(1-8) group: at 5 years 65% vs 44% (P = 0.059). CONCLUSIONS: The study confirmed that RT reduces the risk of local recurrence but without a statistically significant reduction in mortality. The lack of a survival benefit may somehow reflect the dose reduction in CMF(1-21). The evidence that CMF(1-8) offers undoubtable advantages over the CMF(1-21) regimen in OS and, perhaps, in distant control suggests that the dose intensity of CMF in this setting may also be important. In fact, although many CMF(1-8) patients received a dose intensity lower than 100%, 95% of them received a dose intensity higher than the maximum one of the CMF(1-21) patients. Although our results should be interpreted with caution, they seem to provide further rationale for testing the association of postoperative radiotherapy and the CMF(1-8) regimen in stage II breast cancer with positive nodes and treated with demolitive surgery, as already done in the conservative management of breast cancer, also in view of the new support therapies now available (i.e. hematologic growth factors).

Continuous infusion of carboplatin during conventional radiotherapy treatment in advanced squamous carcinoma of the cervix uteri IIB-IIIB (UICC). A phase I/II and pharmacokinetic study.

OBJECTIVE: A prospective, single-arm phase-I/II trial performed to assess the efficacy and toxicity of the concomitant use continuous infusion of low-dose carboplatin and pelvic conventional radiotherapy in patients with locally advanced squamous cell carcinoma of the cervix. MATERIALS AND METHODS: Between January and July 1994, a total of 12 patients consecutively diagnosed to have squamous cell carcinoma of the cervix uteri stages IIB-IIIB UICC-TNM (five patients, IIB; and seven patients, IIIB) entered the study. All patients were evaluated by a gynecologist and a radiation oncologist and were submitted to standard pretreatment staging procedures. Radiation was delivered with 10-MeV photon beams with the shrinking-field technique. The patients received 2 Gy radiotherapy daily, 5 fractions per week, up to a planned total of 60 Gy in 6 weeks to the primary tumor and 46 Gy in 4 weeks to the whole pelvis. Irradiation was performed using four fixed orthogonal fields. One intracavitary insertion, 8 Gy to point A (dose rate, 1.1 Gy/h), was performed immediately after external pelvic irradiation. Carboplatin (12 mg/m2/day) was also administered in a continuous infusion, starting 1 day before the first fraction of radiotherapy. The platinum in plasma and urine, as well as the platinum concentration in the cytosols of lymphocytes and tumor, was measured weekly. RESULTS: A complete response was seen in nine (75%) of the 12 patients. Of the nine patients who achieved a complete remission, only one had subsequent failure in the pelvis. The total pelvic failure rate was 33.3% (four of 12 patients). With a median follow-up time of 20 months, the actuarial survival rate at 24 months was 64.8%. All patients completed the treatment without major protocol violations. Grade-2 leukopenia (in nine patients) and grade-1 nausea and vomiting (in five) were the most common acute toxicities. There was one grade-3 hematologic toxicity. Grade-3 late complications were observed in 16.6% of cases (two of 12 patients). On days 28 and 42 of the treatment, the mean total platinum plasma concentrations were 491 micrograms/L (SD = 129) and 672 micrograms/L (SD = 160), and the ultrafilterable fraction was 8-10%. At the same time points, the concentration in lymphocytes was constant at 21 picograms (pg) platinum/lymphocyte. The levels of platinum concentration measured on days 14 and 28 in the cytosols of tumor cells were 0.3 microgram/g (SD = 0.1) and 0.93 microgram/g (SD = 0.2). CONCLUSION: The combination of continuous infusion of carboplatin and radiotherapy at the aforementioned doses in patients with locally advanced cervical carcinoma resulted in a relatively low frequency of significant acute and late complications. Platinum in normal tissue (picograms per lymphocyte) was stable from week 1 of treatment, whereas the platinum steady state in plasma and in tumor cells was not reached in 6 weeks and was below that required in vitro to produce radiopotentiation. Further studies to determine the optimal dose of carboplatin and irradiation are needed prior to the initiation of phase-III studies.

Carcinosarcoma of the uterus: a clinicopathological multicenter CTF study.

The purpose of this paper is to retrospectively analyze the clinical and pathological data of 118 cases of uterine carcinosarcoma. Prognostic factors and management were evaluated. chi 2 and log-rank tests were performed. Surgical stage at time of surgery was the most important prognostic factor (P < 0.0001); in stage I-II disease depth of myometrial invasion and lymphatic/vascular space involvement were significantly related to outcome, whereas other factors were not useful. In stage I-II patients postoperative radiation did not improve 5-year disease-free survival. Survival curves in patients with advanced disease treated with cisplatin-containing regimens or with doxorubicin (without cisplatin)-containing regimens were overlapping.

[Intracavitary brachytherapy in esophageal neoplasms. Experience at the Radiology Institute of Brescia]. / La brachiterapia endocavitaria nelle neoplasie esofagee. L'esperienza dell'istituto del Radio di Brescia.

We investigated the role of brachytherapy in the management of esophageal cancer. From March, 1990, to December 1994, seventy patients, with biopsy-proved esophageal carcinoma, were treated with brachytherapy +/- external beam radiotherapy. According to the TNM staging system, 24 patients were graded as T1, 24 as T2, 10 as T3, 9 as T4, and 3 as Tx. Median Karnofsky score was 80. Dysphagia was the major symptom in 68% of cases. Treatment consisted of low dose rate first, and then high dose rate brachytherapy, with progressive optimization of doses and fractions, up to total doses of 15-30 Gy in low dose rate and 7-21 Gy in high dose rate. When associated, external beam radiotherapy was delivered with conventional schedules. Tolerance to treatment was good with slight acute toxicity. Symptoms were markedly improved, with reduction of dysphagia in 100% of cases. Overall survival was 75%, 47%, 23% and 18% at 6, 12, 24, 36 months; no significant difference was found between low and high dose rate groups. Furthermore, no difference was shown in the overall survival of the group treated with brachytherapy alone and the one with associated external beam radiotherapy. Late toxicity occurred in 10% of patients and was managed by endoscopic procedures in all cases. In our opinion, brachytherapy appears to be an effective palliative treatment; its role as radical treatment remains to be defined.

[Management control and operative outcome of the Radio Institute "O. Alberti." Management of oncologic follow-up]. / Il controllo della gestione e il bilancio operativo dell'Istituto del Radio "O. Alberti". La gestione del follow-up oncologico.

Post-treatment cancer patient surveillance is an area with few given standards where the need of guidelines has become imperative with the recent emphasis on controlling the ever-increasing health care cost. Unfortunately, literature reports are often inconclusive and ambiguous, mostly because of the lack of properly controlled trials comparing the cost and benefits of various follow-up protocols. In addition, the actual impact on patient survival and quality of life is questionable. At the Istituto del Radio "O. Alberti" (IRA), we consider the follow-up as a sort of population screening aimed at the early detection and treatment of recurrent disease. While aggressive surveillance undoubtedly detects some cancers before symptoms develop, it is debated whether the impact on survival and quality of life are measurable. The early detection of relapse is only a potential survival benefit if recurrent disease is curable with further treatment or at least if salvage treatment is more effective in patients with less severe disease. We investigated the effectiveness, efficacy and medical care of our follow-up protocol. April to June, 1996, we examined 1,223 of 2,148 expected patients; 225 patients disattended the scheduled visits. IRA spent about It. L. 33,800 per examination. Fifty-seven patients were hospitalized to carry out treatment and IRA hospitalization charges were about It. L. 1,100,000 while overall social expenses were about It. L. 6,600,000. Regular visits to see an oncologist provide easy access to specialist medicine and convey a sense of being looked after with a caring system. 94.5% of patients prefers to continue the follow-up program with scheduled visits. Most patients (70%) know about the examinations they undergo but consistently overestimate the importance of laboratory tests and imaging findings and underestimate the importance of medical history and physical examination. In addition, most patients (95%) misinterpret the term "normal" relative to a test result. This study suggests that patients are unfamiliar with the limitations of more costly diagnostic and follow-up studies, which reflects the fact that physicians spend little time discussing follow-up strategies with their patients, especially regarding the cost-benefit analysis and the sensitivity and specificity of the laboratory tests and imaging examinations. Finally, in our opinion follow-up cost is acceptable even though expenses should be reduced optimizing the request of instrumental examinations. Therefore, oncologists should definitely try to inform their patients about the clinical importance of follow-up.

Endoscopic treatment of malignant airway obstructions in 2,008 patients.

We report our 13-year experience with endoscopic treatment of malignant obstructions of the airway by Nd:YAG laser, stents, and intraluminal brachytherapy in 2,008 patients. We performed 2,610 laser resections in 1,838 patients, 66 high dose rate brachytherapies, and we placed 393 tracheobronchial silicone stents in 306 patients. We used the rigid bronchoscope in 96% of the laser procedures and in all cases requiring stent placement; general anesthesia was given to 90% of these patients. Endobronchial radiotherapy was performed under local, anesthesia. In 93% of patients undergoing laser resection, we obtained an immediate patency of the airway with consequent improvement of quality of life. The median time between the first and second laser treatment was 102 days, being longer in the case of stent placement (when required) or in association with brachytherapy. Even if endoscopic treatment should be considered only for palliation, laser vaporization could be curative in case of in situ carcinoma. Since 1983, we have treated 23 such lesions in 17 patients and up to now, none has recurred. Finally, endoscopic resection may allow a better assessment of the true extent of the tumor, shifting to surgery patients originally considered to have inoperable disease or allowing lung-sparing operations (21 and 18 patients of our series, respectively). The total mortality rate was 0.4% (12 patients over 2,798 treatments; 2,710 Nd:YAG laser + 151 stents without laser + 37 brachytherapies without laser) in the first week after the procedures, and was mainly related to cardiovascular problems and respiratory failure. In conclusion, endoscopic resection of lung malignancies is rapid, effective, repeatable, and complementary to other treatments; although it should be considered only palliative, laser resection could be curative in patients with in situ carcinomas and early cancers. Laser, stents, and endoluminal brachytherapy should be available in all centers with major experience; a well-trained team is mandatory to plan the most appropriate treatment and manage any possible complication.

High-dose-rate brachytherapy for poor-prognosis, high-grade glioma: (phase II) preliminary results.

AIMS AND BACKGROUND: The purpose of this study was to investigate the palliative effectiveness of an interstitial fractionated high-dose-rate (HDR) brachytherapy regimen in patients with poor-prognosis, high-grade glioma. METHODS: An after-remote-loading microSelectron HDR lr-192 370 GBq unit was used. A unique coaxial after-loading catheter was stereotactically inserted through the center of the target volume. The treatment schedule was: 5 fractions, 5 Gy per fraction, or alternatively 7 fractions, 3.85 Gy per fraction, at the dose specification surface, 2 fractions per day. Twenty-four patients have been treated: in 17 of them (T1 G3-4) the catheter was implanted during stereotactic biopsy procedure; in the other 7 cases (T2 G3-4), subjected to partial resection and reduced to yT1, the catheter was implanted following surgery with a mean delay of 15 days. RESULTS: The treatment was feasible and well tolerated. The complete course takes no more than 7 days. The acute complication rate (2/24) seems to be acceptable. The median survival was 8 months. No less than 45% of the patients had a WHO grade 2 score or better at any time of follow-up. At 4 months of follow-up, functional status, assessed using a verbally administered Barthel index, had improved from the pretreatment level in 29.1% of the 18 surviving patients and remained stable in another 22.2%. A minimal response or stable disease, according to CT scan, was obtained in about half of the assessable survivors at any time of follow-up. CONCLUSIONS: The short course of brachytherapy provides a good palliation in terms of functional improvement in a high proportion of patients, with low and acceptable toxicity.

[Locally advanced carcinoma of the cervix uteri (stage IIB-IIIB TNM-UICC): radiotherapy combined with simultaneous daily low-dose platinum. Phase II study]. / Carcinoma della cervice uterina localmente avanzato (stadio IIB-IIIB TNM-UICC): radioterapia in associazione a basse dosi concomitanti e giornaliere di platino. Studio della fase II.

A prospective, single arm, phase-II trial was performed to assess the efficacy and local toxicity of the combination of low doses of platin and pelvic radiotherapy in patients with locally advanced carcinoma of the cervix. January, 1993, through August, 1994, twenty-three previously untreated patients with squamous carcinoma (stages IIB-IIIB UICC) entered the study. All patients were examined by a gynecologist and by a radiation oncologist and then submitted to conventional pretreatment staging procedures. Nine patients were classified as stage IIB and 14 patients as stage IIIB. Radiotherapy consisted of 60 Gy external beam irradiation (46 Gy to pelvis + 14 Gy boost to cervix uteri and parametria) plus one low dose rate intracavitary treatment to a dose of 8 Gy to point A. Cisplatin (3 mg/m2/day) or carboplatin (12 mg/m2/day) was also given for 6 weeks starting on radiotherapy day 1. The treatment was well tolerated and no patient required radiotherapy discontinuation. With a median follow-up time of 20 months, complete response was seen in 74% (17/23) of the patients. One of the 17 patients who achieved a complete remission, during follow-up, relapsed in the pelvis and one developed lung metastases. Total failure rate in the pelvis was 30.5% (7/23). Distant metastases were observed in 17.5% (4/23) of the patients. Actuarial overall and disease-free survival rates at 33 months were 69.1% and 65.2%, respectively. Late gastrointestinal toxicity (grade 3) occurred in 8.6% (2/23) of patients, with one patient developing a rectal ulcer-which was submitted to colostomy- and one patient a vaginal necrosis. The combination of platin and radiotherapy appears to be an effective regimen for the patients with locally advanced carcinoma of the cervix and caused a relatively low rate of late gastrointestinal complications.

Extended radical hysterectomy in early-stage carcinoma of the uterine cervix: tailoring the radicality.

The question of whether surgical treatment in early-stage cervical cancer should be aggressive or restricted to less radical techniques is still controversial. To answer this question it was thought useful to investigate the correlation of parametrial lymph node metastases with extension and stage of disease. Two-hundred and sixty-three consecutive primary radical surgical procedures were performed in our institute in clinical stage IB or stage IIA cervical cancer. Positive parametrial nodes were found in 6.9% of cases: 5% in stage IB (3% in the proximal part of the parametrium and 2% in the distal part, near the pelvic wall) and 16.3% in stage IIA (7% proximal and 9.3% distal) (P = 0.0193). During a median follow-up period of 92 months, disease recurred in 17.1% and 17.6% of cases, in negative and positive parametria, respectively. The 5-year overall and disease-free survival rates were 80.4% and 81.6% for patients with negative and positive parametria, respectively. From this experience it is concluded that the extent of radical hysterectomy should be related to the extent of the disease on the basis of modern knowledge of the pattern of spread. The principal key to prognosis remains pelvic and paracavoaortic nodal status.

High-dose interstitial brachytherapy for glioblastoma multiforme.

AIMS AND BACKGROUND: The long-term prognosis for survival of patients with inoperable glioblastoma multiforme (GBL) is very poor. Conventional external radiotherapy gives only transitory result. This severe prognosis led us to elaborate a high-dose rate (HDR), after-remote-loading brachytherapy treatment protocol: our aim was both therapeutic and psychologic. METHODS: Five patients with GBL (T1 G4 UICC) were treated with stereotactic biopsy followed by HDR brachytherapy. A unique coaxial after-loading catheter was stereotactically inserted through the center of the target volume. The treatment schedule considered 5 fractions, 5 Gy/fraction at the dose specification surface, 2 fractions per day. RESULTS: The treatment was well tolerated. Tumor progression started again at the 8th to the 16th week from the end of the treatment. ECOG performance status at the 8th week was better than before the therapy in 2 of 5 patients and was stable in 2 of 5 patients. Order neuroperformance status was stable in 2 patients at 8 weeks. At the 16th week there was neurologic deterioration. The average survival was 21 weeks. CONCLUSIONS: Our approach seems to be of some interest for the palliation of GBL, and it offers some advantages, in particular regarding the short treatment period. Our procedure can be improved: a multi-catheter implant and a more fractionated schedule could be taken into account.

Adjuvant therapy in stage-I epithelial ovarian cancer: an open question.

From January 1980 to December 1991, 137 patients suffering from Stage I EOC, were treated in our Institute. All patients underwent primary surgery with intensive staging procedures in 82% of cases; 12 patients underwent USO. Sixty-one out of 137 patients did not receive complementary treatment, 66 patients were treated with chemotherapy and 10 patients with i.p. P32. Three risk categories were identified, according to stage and grade: R1 = Stage IA-B G1 (45 cases); R2 = Stage IA-B G2-3 (31 stage); R3 = Stage IC all grades (53 cases). Forty out of 45 R1 cases did not receive adjuvant therapy; 12/31 R2 cases underwent surgical treatment only, 16/31 received adjuvant chemotherapy and 3/31 i.p. P32; 39/53 R3 patients were treated with chemotherapy and 6 with i.p. P32. Twenty-six patients (18.9%) suffered from a neoplastic relapse. Overall actuarial 5- and 10-year survival was: R1 = 96.3% and 89.9%; R2 = 79.6% and 79.6%; R3 = 79.2% and 62.3% respectively. There was no difference in survival between R2 treated and untreated patients, while difference emerged in R3 patients between chemotherapy and i.p. P32 groups. Five-year actuarial survival for the 26 patients suffering from recurrence was 40.5%.

[Chemo-radiotherapy in advanced head and neck tumors. Personal experience]. / La chemio-radioterapia nei tumori avanzati del capo-collo. Esperienza personale.

From January 1981 through December 1983, 49 untreated patients with locally advanced head and neck cancers were randomized in two groups to receive different radiochemotherapy regimens. Group A, including 29 cases, received 4 cycles of induction chemotherapy with Bleomycin, Methotrexate and Hydroxyurea before definitive external radiotherapy (60 Gy); group B, including 20 patients, received the same total dose of radiotherapy but the 4 cycles of chemotherapy, as described above, were administered between the 20- and the 40-Gy doses. Both groups were compared with a control group treated in the same period with radiotherapy (60 Gy) alone. The response to treatment was evaluated at the end of chemotherapy or radiotherapy alone and at the end of combined regimens. Long-term survival rates were analyzed for all groups relative to complete tumor response, disease-free interval and time to disease progression. In our experience the radio-chemotherapy combination, according to the described schedules, failed to improve both local control and overall survival; the comparison with the control group does not suggest that induction or intercalated chemotherapy can increase long-term survival even if initial complete and partial response rates are high.

[Exclusive radiotherapy in the treatment of carcinoma of the portio cervicis, stage IIB FIGO]. / La radioterapia esclusiva nel trattamento dei carcinomi della portio allo stadio IIB FIGO.

From January 1970 through December 1987, 135 patients with cervical cancer in stage IIB (FIGO criteria) were treated by means of exclusive radiotherapy in the Istituto del Radio of the Brescia University. Thirty cases were treated by exclusive external-beam radiotherapy (RTT), 39 by brachytherapy (CU) plus external-beam radiotherapy, 24 by combined RTT and CU, 41 by RTT + CU + RTT, and 1 case by CU alone. Crude survival at 5 years is 52.4%, and NED survival is 50%. The differences between the values of crude and NED survival by radiotherapy technique were statistically significant (p 0.05), ranging from 69.8% in the RTT + CU group to 35.5% in the RTT alone group. Twenty-four cases (18%) failed to obtain complete remission, and 24 more cases recurred in the pelvis. Sequelae were evaluated by the French-Italian glossary; they were present in 62 cases (46%), but in 12 cases only (9%) they were severe. The incidence of sequelae was highest in the groups of patients treated with the combined techniques (RTT and CU) which allowed best disease control.

[Rhinopharyngeal carcinoma. Clinical prognostic factors]. / Carcinoma rinofaringeo. Fattori prognostici clinici.

The authors report the results of the retrospective analysis of 306 patients with nasopharyngeal carcinoma. All patients had received high-dose radiation therapy. First, overall results were analyzed, and then the prognostic value of the patients' data (age and sex) and of tumor features (histology, local spread, lymph node involvement). Crude actuarial survival rate is 42.9% (+/- 2.9) at 5 years; loco-regional control at the end of treatment was obtained in 16.8% of cases; 53.6% of them (126 patients) had relapses, especially on T and M. Cumulative relapse rate was 51.1% (+/- 3.3) at 5 years. Mean relapse-free interval was 10 months. All the clinical factors we examined had prognostic value; especially local tumor spread, with a worse prognosis for tumors with extra-nasopharyngeal spread (5-year survival: 38.3% +/- 6.9 for T3 and 33.9% +/- 4.8 for T4), and especially for tumors with neurological deficits (5-year survival: 19.9% +/- 6.3). Regional lymph node metastases were an important factor too, with a special emphasis on size (5-year survival: 26.4% +/- 6.5 in the cases with adenopathies with phi greater than 6 cm), and fixed adenopathies (5-year survival: 23.9% +/- 4.6). These prognostic factors are considered only in part in the current TNM 1987 staging system, which calls for its partial revision.

[Exclusive radiotherapy of stage Ib cervix carcinoma]. / La radioterapia esclusiva del cervicocarcinoma stadio Ib.

From January 1st 1970 to December 31 1987, 178 consecutive cervical cancer Ib patients were treated at the Istituto del Radio, University of Brescia, by means of radiotherapy alone. In spite of the negative selection of the patients (advanced age, poor general conditions, associated pathologies) the results were good: 5-year cumulative survival was 86.5%, with a total failure rate of 13.5% (24 failures: 18 in the pelvis, 3 metastases and 3 both). The incidence of major complications (G2-G3-G4 of the Italian-French glossary) was 20% (36 patients): 19 G2, 15 G3 and 2 G4. The results in terms of survival and complications were related to the prognostic factors of the tumor (histology, grading, tumor size), of the patient (age, Karnofsky scale, associated pathologies, number of erythrocytes and hemoglobin rate) and treatment modalities (total dose, fractionation, combination of intracavitary brachytherapy and external beam).

[Radiotherapy of locally advanced tumors of the mouth floor and the tongue]. / La radioterapia dei tumori localmente avanzati del pavimento orale e della lingua.

At Istituto Radio "O. Alberti" in Brescia 312 patients with locally advanced cancers (T3-4N0 and T1-4N1-3) of the tongue or floor of the mouth were treated between 1970 and 1985. All underwent high energy radiotherapy associated, in 93 cases, with surgery on the T and/or on the N. The cases were divided by T and N in order to evaluate the prognostic importance of these parameters. Total remission (TR) at the end of treatment was achieved in 52% of the cases (163 patients). A relationship was found between tumor size, degree of lymph node involvement and the likelihood of response. Of the 163 cases in TR, 89 (55%) showed recurrence; 80% taking place within the first two years. After correction for natural death, the actuarial 5 year survival rate for the entire case study proved to be 27% while NED was 22%. The group undergoing radiotherapy in association with surgery showed a better survival rate than the group which only underwent radiotherapy (45% vs. 20% at 5 years). In the cases of advanced T (T3-4) lymph node involvement did not appear to affect prognosis.

[Significance of preventive radiotherapy of the neck in clinically N0 tumors of the larynx]. / Il significato della radioterapia precauzionale sul collo nei tumori della laringe clinicamente N0.

The role of precautionary radiotherapy of the neck in laryngeal cancers (except T1-T2 glottic and some T1 supraglottic cancers) N0 at the clinical staging was investigated. Two-hundred and fifty-three patients were examined: 143 were irradiated only on T, and 110 also on the neck. Radiotherapy of the neck in the latter group was performed either by means of two large opposed fields of photon beams including T and N, or by means of fields of photon beams on T and electron beams (8 x 12 cm2 average) on the neck, to quite exclude any risks for the spinal cord. The dose was 45-50 Gy (2 Gy/fraction/day; 5 fraction/week) in 4-5 weeks. A comparison of the results obtained in the two groups, in terms of survival-rate and relapse-free time, indicates that radiotherapy reduces the change of relapses on N (6.1% vs. 14.62% at 3 years; p = 0.04) and improves the patient's survival chances (82.5% vs. 68.4% at 3 years; and 80.8% vs 63.4% at 5 years). Our data were then compared with literature data on the importance of N field size in radiation treatment. As a rule, some authors enlarge the field to be treated to a total nodal neck irradiation, but their results are not significantly different from those we obtained with 8 x 12 cm2 field size.

Treatment of primary invasive cervical cancer. Considerations on 997 consecutive cases.

From 1965 to 1979 997 consecutive cervical cancer patients were treated at the University of Brescia. Stage I B and II A low risk patients underwent radical surgery, followed by Co60 external pelvic radiation when positive nodes and/or adverse pathological factors on the specimens were encountered. In stage I B the 5-year survival was 95.9% and 82.7% in the two groups and in stage II A 93.3% and 76.5% respectively. Bulky and large tumors were treated by intracavitary radium followed by radical hysterectomy and, if indicated, by Co60 external beam pelvic radiation. All other patients and all stage II B were treated by radiotherapy. The results of primary radical surgery may reflect the favourable preselection of cases. Postoperative radiation teletherapy in case of adverse pathological factors is of benefit to the patients.