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A brief summary and overview of brachytherapy in its historical evolution provides the basis for a deeper understanding of the present role and challenges of the discipline. Confronted by those challenges, brachytherapy still remains a solid and effective method of cancer treatment, and it must be known to all those who want to take part in that treatment. Based on this review of the history of brachytherapy, the present challenges and the possible trends of development are presented, and want to serve as the basis for a complete understanding of what will be discussed in all the chapters of this book. From what has been done in the past, from knowing what challenges are today dealing in cancer treatment, it would be possible to redesign the role of brachytherapy and once again promote both its role in a complete formation of new generation of radiation oncologists and its rationale use in clinical practice.

With the discovery of radium by Curie in 1898, researchers recognized that this unique radionuclide had specific biologic properties that were applicable to treating patients with cancer. In the beginning, the radium sources were placed within cavities as independent sources and, when needles were available, implanted into tissues. The first combination of brachytherapy technologies with external-beam radiation therapy was reported by Wright at the Memorial Sloan-Kettering Cancer Center in New York in 1914 in the treatment of a patient with cervical cancer. Next, there was a rapid implementation of brachytherapy in the treatment of cancer by intracavitary placement of radionuclides, interstitial implantation technologies, and systemic administrations. With the development of new radionuclides, including cesium-137, cobalt-60, iridium-192, iodine-125, palladium-103, ruthenium-109, strontium-90, iodine-131, and californium-225, which had varying types of radiation emissions appropriate when properly selected in treatment of cancer, there was a rapid development of innovative technologies to treat all malignancies, especially gynecologic cancer. The evolution of events brought forth new applicators and techniques that allowed for better distribution of the radiation dosage within the tumor being treated, safer use of radionuclides, and the development of computer programs allowing for varying source applications and dose distributions within the volume implanted.

Purpose : A new method of palliation of malignant obstructive jaundice is presented. Methods and Materials : Twelve patients with carcinoma of the extrahepatic bile ducts (EHBD-five patients) or pancreatic head (PH-seven patients) received radiation therapy between 1988 and 1991. Percutaneous transhepatic biliary drainage was performed in four EHBD patients and an endoprosthesis was placed during endoscopic retrograde cholangiopancreatography (ERCP) in the other eight patients. All 12 received intraluminal brachytherapy (ILBT) : 20-50 Gy calculated at 1 cm from the Iridium-192 ( 192 Ir) wire. In four PH patients the source was placed in the duct of Wirsung ; in the other eight patients ILBT was performed via the common bile duct. Five of the seven PH patients and one of the five EHBD patients received External Beam Radiation Therapy (EBRT) : 26-50 Gy, alone or with concomitant 5-Fluorouracil (5-FU). Results : Cholangitis occurred in six patients. Three PH patients treated with EBRT + ILBT developed gastrointestinal toxicities. With a minimum follow-up of 18 months, median survival times were 14 months (EHBD) and 11.5 months (PH) ; one of the seven PH patients is alive (29 months) and two of the EHBD patients are alive (18 and 43 months). All patients had satisfactory control of jaundice. Conclusions : The results in the EHBD patients suggest that the addition of ILBT after biliary drainage prolongs survival. Further experience is necessary to determine whether ILBT in the common bile duct and/or in the duct of Wirsung may be, in PH patients, an alternative boost technique to Interstitial Brachytherapy (IBT) or Intraoperative Electron Beam Radiation Therapy (IOEBRT).

The results obtained with interstitial brachytherapy in thirty-six low-grade cerebral gliomas (2 pilocytic astrocytomas, 23 astrocytomas and 11 oligodendrogliomas) are reported (mean follow-up: 75 months, range 37-159). All tumours were situated in locations which did not call for surgical removal as the treatment of choice. Their volume ranged from 4 to 82 cc (m = 32); the Karnofsky performance status (KPS) of the treated patients lay between 0.60 and 0.90. The sources utilized (Iridium-192 in 32 cases and Iodine-125 in 4) were implanted permanently in 22 patients and temporarily in 14, using the Talairach stereotactic apparatus. The mean peripheral dose was 89.7 Gy for the permanent implants and and 42.8 Gy with a rate of 32.05 cGy/h for the temporary implants. External beam irradiation was added for tumour volumes greater than 35 cc (19 cases) on a second target volume extending 2 cm beyond the tumoural borders treated with interstitial irradiation. The survival estimates for the entire group showed a probability of 82.9% at 60 months, of 56.8% at 96, 39.4% at 120 (m.s.t.: 112 months). The quality of life in the treated patients was satisfactory, KPS never falling below a mean score of 0.70. The extent of the target volume turned out to be the most significant factor influencing survival at the multivariate analysis. Severe neurological impairment due to radionecrosis occurred in 4 patients (11%), three of them requiring surgical decompression.(ABSTRACT TRUNCATED AT 250 WORDS)

Since 1975, seven groups of investigators have reported clinical results of interstitial brachytherapy (IBT) for pancreatic cancer. The reports are comprised of data from 254 patients, 21 of whom died in the postoperative period for an overall operative mortality rate of 8.7%. Operative mortality rate range from 0% to 32% in individual reports. Most patients have been treated with 125I, although 25 patients were treated with 198Au seeds. Most investigators report combining IBT with external beam radiation therapy (EBRT) +/- adjuvant chemotherapy. In general, IBT has been associated with considerable morbidity. Median patient survival time has not exceeded 15 months. This report describes an additional seven patients with locally unresectable pancreatic cancer, without distant metastases, treated primarily with 60 to 100 Gy matched peripheral dose (MPD) by 125I IBT. One patient died postoperatively of a pulmonary embolus. Four of the remaining six patients were also treated with modest doses (10.5 to 30 Gy) of EBRT late in the course of the disease for local tumor progression. One developed a pancreaticocutaneous fistula, and one developed exacerbation of pre-existing diabetes mellitus. The median patient survival time from the date of IBT was 7 months (range: 0 to 21 months). One patient is alive without clinical evidence of cancer 9 months after IBT.

A rapidly and constantly increasing aged population in the western countries poses a wide range of specific problems to oncologists. A different way to face medical issues should be sought for older patients with cancer, looking at the characteristics that are peculiar to the elderly from different points of view. Brachytherapy is an effective form of radiotherapy which, for its specific characteristics, may be a valid alternative to more complex modalities of treatment, thus allowing a better sparing of normal tissues and structures yet achieving a similar tumor control rate. This paper reviews the literature on the subject of cancer treatment in the elderly, focusing on radiotherapy and brachytherapy, to evaluate the current attitude toward this problem in the medical community and to see if it is possible to identify a patient population that will benefit from this technique.

Purpose: Cancers of the extrahepatic biliary tract are rare. Surgical resection is considered the standard treatment, but is rarely feasible. Several reports of combined modality therapy, including external beam radiation, often combined with chemotherapy and intraluminal brachytherapy, have been published. The purpose of this study was to evaluate the effect of chemoradiation plus intraluminal brachytherapy on response, local control, survival, and symptom relief in patients with unresectable or residual extrahepatic biliary carcinoma. Methods and Materials: From February 1991 to December 1997, 20 patients (14 male, 6 female; mean age 61 ± 12 years; median follow-up 71 months) with unresectable (16 patients) or residual (4 patients), nonmetastatic extrahepatic bile tumors (common bile duct, 8; gallbladder, 1; Klatskin, 11) received external beam radiation (39.6–50.4 Gy); in 19 patients, 5-fluorouracil (96-h continuous infusion, days 1–4 at 1,000 mg/m 2 /day) was also administered. Twelve patients received a boost by intraluminal brachytherapy using 192 Ir wires of 30–50 Gy, prescribed 1 cm from the source axis. Results: During external beam radiotherapy, 8 patients (40%) developed grade 1–2 gastrointestinal toxicity. Four patients treated with external-beam plus intraluminal brachytherapy had a clinical response (2 partial, 2 complete) after treatment. For the total patient group, the median survival and time to local progression was 21.2 and 33.1 months, respectively. Distant metastasis occurred in 10 (50%) patients. Two patients who received external beam radiation plus intraluminal brachytherapy developed late duodenal ulceration. Two patients with unresectable disease survived more than 5 years. Conclusion: Our data suggest that chemoradiation plus intraluminal brachytherapy was relatively well-tolerated, and resulted in reasonable local control and median survival. Further follow-up and additional research is needed to determine the ultimate efficacy of this regimen. New chemoradiation combinations and/or new treatment strategies (neoadjuvant chemoradiation) may contribute, in the future, to improve these results.

To evaluate intraluminal brachytherapy (ILBT) in patients with extrahepatic bile duct or pancreatic cancers.Thirty-one patients (aged 33-87 years) with unresectable extrahepatic bile duct (n = 18) or pancreatic (n = 13) cancer received ILBT exclusively or as part of a definitive treatment regimen. ILBT was performed with transhepatic percutaneous drainage in four patients and with endoscopic retrograde cholangiopancreatography in 27. Fourteen patients with no metastases, an Eastern Cooperative Oncology Group performance score ofor = 2, and good hematologic parameters received combined modality treatment: 30-Gy ILBT and 45-Gy external-beam radiation therapy with continuous infusion of fluorouracil. Seventeen patients underwent 50-Gy ILBT alone for palliation.No direct treatment-related acute toxic reactions were seen. Three patients had cholangitis early in the study. Three patients had late gastrointestinal bleeding. Jaundice was palliated in all patients (n = 29); pain, in 11 of 13 patients. The survival rate in patients with extrahepatic bile duct cancer was 62% (five of eight) at 2 years for combined modality treatment. No patient with pancreatic cancer lived for longer than 2 years.ILBT is an effective palliative treatment of unresectable extrahepatic bile duct and pancreatic cancers. Results suggest a possible "curative" role in specific clinical settings when properly integrated with other treatments.

Brachytherapy has been used for pancreatic cancer for over eight decades. Appositional, interstitial and intraluminal applications have been employed. Data from approximately three hundred cases are summarized in this review. The most common form of brachytherapy. Although this procedure, when combined with external beam radiation therapy and systemic chemotherapy, provides the best possible local control of pancreatic cancer, it is a hazardous procedure in most hands. Hopefully, the new techniques, such as intraluminal brachytherapy and infusional brachytherapy, will less prone to serious complications and they will prove to be efficacious in the management of cancer of the pancreas.

Prostate cancer is the most common as well as the most frequently irradiated malignancy involving the genitourinary tract. In 1995, the American Cancer Society anticipates that in the United States there will be 244 000 new cases diagnosed with 40 400 deaths due to the disease process American Cancer Society 1995). In addition, it is among the most successfully treated cancers of the genitourinary tract in terms of both definitive outcome and metastatic presentations.

The adequacy of an interstitial implant carried out with a new radioactive source, the 169 Yb seed model X1267, has been examined by computing volumetric indices based on dose-volume histograms. The comparison of these indices with the ones computed for 125I seed implantations shows that the use of ytterbium seeds presents an improvement of the dose homogeneity in interstitial implants. This is due to the significant build-up associated with 169 Yb photons that reduces the rapid dose fall-off with the distance from the source. Moreover, relative to 192Ir, the lower photon energy gives 169 Yb the advantage in clinical use of reduced radiation exposure (i) to health care workers, (ii) to relatives of treated patients and (iii) to healthy neighbouring tissues of the patients if appropriate thin shielding is used.

Intraluminal brachytherapy (Il-BRT) consists in the treatment of neoplasms by the positioning of radioactive sources in the lumen of cavitary organs such as the esophagus, the trachea, the bronchi and bile ducts. This procedure has been used to deliver relatively high doses of irradiation to bile duct and periampullary carcinomas while sparing the adjacent organs. Results of a number of reports appeared in the last fifteen years document the feasibility and tolerance of the procedure. Moreover these data seem to suggest that Il-BRT is able to prolong the survival of patients undergoing biliary drainage and that its use as boost dose in external beam radiotherapy (ERT) enhances the results of the latter. Combined ERT+Il-BRT is associated to an incidence of gastrointestinal ulcerations related to the total dose delivered. Better patient selection and standardization of reference dose represent prerequisites for testing this procedure in prospective randomized trials.

The preliminary results obtained in 19 patients treated with interstitial irradiation for malignant gliomas are reported. Three different groups are included in the study: I Newly diagnosed tumours not suitable for surgery: 13 cases (10 anaplastic astrocytomas (AA) and 3 glioblastomas (GBM), mean volume 46.56 cc, source Ir 192) were implanted permanently (n = 11, mean peripheral dose 93.54 Gy) or temporarily (n = 2, 50 Gy = 0.5 Gy/hr). External beam irradiation was additionally applied in all cases. II Residual or recurrent tumours: 5 patients (2 AA and 3 GBM, mean volume 7.2 cc, source Ir 192) received temporary implants (150 Gy peripheral dose = 1.5 Gy/hr) after surgery and conventional radiotherapy. III Newly diagnosed surgically removable tumours: only one patient with AA (15 cc volume, source Ir 192) received temporary implantation with the same dose regimen used in Group II before surgery and external beam irradiation. A median survival time of 26.75 mos (34.62 mos for AA, with 3 long-term survivors) was observed in the patients of Group I. Three patients of Group II are still alive after 8, 12 and 12 mos after brachytherapy, the other 2 (GBM) survived 7 and 12 mos. The single patient so far included in Group III is still alive after 6 mos. Although the study is still in progress, these preliminary data seem to indicate that interstitial radiotherapy can be effective in prolonging survival of patients with malignant gliomas.

The preliminary results obtained in 19 patients treated with interstitial irradiation for malignant gliomas are reported. Three different groups are included in the study: I Newly diagnosed tumours not suitable for surgery: 13 cases (10 anaplastic astrocytomas (AA) and 3 glioblastomas (GBM), mean volume 46.56 cc, source Ir 192) were implanted permanently (n = 11, mean peripheral dose 93.54 Gy) or temporarily (n = 2, 50 Gy = 0.5 Gy/hr). External beam irradiation was additionally applied in all cases. II Residual or recurrent tumours: 5 patients (2 AA and 3 GBM, mean volume 7.2 cc, source Ir 192) received temporary implants (150 Gy peripheral dose = 1.5 Gy/hr) after surgery and conventional radiotherapy. III Newly diagnosed surgically removable tumours: only one patient with AA (15 cc volume, source Ir 192) received temporary implantation with the same dose regimen used in Group II before surgery and external beam irradiation.

Between 1980 and 1988, 16 patients (9 females, 7 males) with malignant neuroepithelial tumors of the brain were treated by brachycurietherapy (BCT) and external radiation therapy (ERT) in a phase II nonrandomized study. There were 13 grade III and 3 grade IV tumors according to the WHO classification. Five patients in the grade III group who showed anaplastic foci in a generally grade II background were separately examined. Six patients received only BCT whereas 10 patients were treated by a combination of BCT and ERT, according to the tumor volume. We utilized as radioactive sources 192Ir in 14 cases and 125I in 2. Thirteen patients underwent permanent implant, 3 others received temporary irradiation with removable afterloaded catheters. The target volume was less than 50 cc in 8 cases, between 50 and 100 cc in 7, and larger than 100 cc in 1 patient. The total dose at the periphery of these volume ranged between 70 and 144 Gy. The result were analyzed referring to the following aspects: performance status, survival, side effects, grading. The impact of BCT was analyzed especially in a grade III with anaplastic foci group which showed a median survival of 6 years compared with only 2 years median survival of the pure grade III group.

Radical surgical intervention is not always possible in vulvar tumours, particularly in infiltrating forms of paraurethral locations. In our case-series, the supplementary performance of Curietherapy, particularly with Radium substitutes (Iridium 192) and following the afterloading method, has enabled us not only to obtain long disease-free periods but also, coupled with the "large volume" of External Radiotherapy, to master forms exceeding the surgical action scope.

Brachicurietherapy represents a low dose-rate irradiation able to deliver high focal doses within relatively small tumor volumes. Its application to brain tumors utilizing the stereotactic techniques is nowadays considered with growing interest. The Authors analyze, on the basis of their personal experience, the possibilities and the limits offered by this therapeutic procedure in neuro-oncology. The choice of the sources and their modality of application, the definition of the optimal dose/time and dose/volume ratio are the main problems taken into consideration and discussed.

Between 1980 and 1987 thirty patients harbouring cerebral neuroepithelial tumours have been treated with stereotactic brachycurie therapy (18 males, 12 females), either alone (n = 16) or combined with surgery (n = 7) and/or external radiotherapy (n = 10). There were 25 slowly growing tumours (grade I n = 1; grade II n = 24). The remaining 5 were malignant tumours (grade III n = 3; grade IV n = 2). The radioactive sources utilized were 192Ir in 26 cases and 125I in 4. Twenty-eight patients underwent permanent implantation, the other two received temporary irradiation with removable after-loaded catheters. Target volume was less than 15 cm3 in 6 cases, between 16-60 cm3 in 17 and more than 60 cm3 in 7. Tumour dose at the periphery of the target volume was: 70-100 Gy in 19 and 100-130 Gy in 9 of the cases treated with permanent implantation; the patients irradiated with removable implants received 40-60 Gy in 5-7 days. General follow-up ranged between 0.3 and 6.9 years (mean = 2.5 years). The results are analyzed with reference to the following aspects: 1) natural history of the disease; 2) modalities and goal of the treatment; 3) place of brachy therapy as sole treatment and combined with the other available therapeutical means.

One hundred patients with pancreatic cancer were evaluated between March 1981 and December 1989. This study showed that 61 were not candidates for definitive surgery because of nonoperability (28 patients) or nonresectability (33 patients). An additional 25 patients had cancers that were unresectable because of metastases (13 patients) or local spread of disease (12 patients) discovered at laparotomy. Fourteen patients had resectable cancers. Ten were treated by total pancreatectomy, three by distal pancreatectomy and one by pancreatoduodenectomy (Whipple). There were two operative mortalities. The median patient survival time was 20.5 months. Two patients survived 5 years. Five patients are alive at 3, 14, 18, and 47 months. Palliative surgical procedures performed in 18 patients included 10 biliary bypasses, 9 gastrojejunostomies, and 6 T-tube placements. This was associated with an operative mortality rate of 11%. The median survival time was 5 months. Other palliative measures included endoscopic placement of biliary and pancreatic stents (47 patients, 2.7% mortality rate), endoluminal radiation therapy, interstitial radiation therapy and external beam radiation therapy. The median survival time of patients so treated was 4.5 months.