GEC-ESTRO recommendations for head & neck cancer brachytherapy (interventional radiotherapy): 2nd update with focus on HDR and PDR.

Modern brachytherapy (BT) is playing an important role in the multidisciplinary treatment of Head and Neck (H&N) cancer, as an organ- and function-preserving therapy. Low-dose-rate (LDR) technology has been replaced by modern remote afterloading and stepping source equipment using pulsed dose rate (PDR) or high dose rate (HDR) sources, improved image guidance and 3D treatment planning systems. This is an update of the previous GEC-ESTRO recommendations for H&N tumors, mainly applied to squamous carcinomas. Indications, results and recommended doses for different tumor sites are presented according to the published studies.

Intraoperative EBRT and resection for renal cell carcinoma : twenty-year outcomes.

PURPOSE: We report the outcomes of a multimodality treatment approach combining maximal surgical resection and intraoperative electron radiotherapy (IOERT) with or without external beam radiation therapy (EBRT) in patients with locoregionally (LR) recurrent renal cell carcinoma (RCC) after radical nephrectomy or LR advanced primary RCC. PATIENTS AND METHODS: From 1983 to 2008, 25 patients with LR recurrent (n = 10) or LR advanced primary (n = 15) RCC were treated with this approach. Median patient age was 60 years (range, 16-79 years). Fifteen patients (60%) received perioperative EBRT (median dose, 44 Gy). Surgical resection was R0 (negative margins) in 6 patients (24%) and R1 (residual microscopic disease) in 19 patients (76%). The median dose of IOERT was 14 Gy (range, 9-15). Overall survival (OS) and relapse patterns were calculated using the Kaplan-Meier method. RESULTS: Median follow-up for surviving patients was 22.2 years (range, 3.6-26 years). OS and DFS at 5 and 10 years were 38% and 18% and 19% and 14%, respectively. LR control (tumor bed or regional lymph nodes) and distant metastases-free survival rates at 5 years were 80% and 22%, respectively. The death rate within 30 days of surgery and IOERT was 4% (n = 1). Six patients (24%) experienced acute or late toxicities of grade 3 or higher according to the National Cancer Institute Common Toxicity Criteria (NCI-CTCAE) v4. CONCLUSION: In patients with LR recurrent or LR advanced primary RCC, a multimodality approach consisting of maximal surgical resection and IOERT with or without adjuvant EBRT yielded encouraging local control results, justifying further evaluation.

Ocular Brachytherapy (Interventional Radiotherapy): Preserving the Vision.

Uveal melanoma represents the most common intraocular neoplasia among adults. Brachytherapy (interventional radiotherapy; IRT) has a great advantage, when compared with enucleation, both in terms of organ and function sparing. The Collaborative Ocular Melanoma Study introduced into clinical practice a standardised procedure that allowed the equivalence of IRT with enucleation in terms of overall survival to be demonstrated. IRT is carried out by placing a plaque in direct contact with the sclera under the uveal melanoma. Several radioactive sources may be used, including 106-ruthenium, 125-iodine, 103-palladium and 90-strontium. It is a multidisciplinary procedure requiring the collaboration of interventional radiation oncologists and ophthalmologists in the operating theatre and medical physicists for an accurate treatment time calculation. It also relies on ultrasound imaging to identify the lesion and verifiy the correct plaque placement. An emerging tool of paramount importance could be the use of artificial intelligence and predictive models to identify those patients at higher risk of developing late side-effects and therefore who may deserve preventive and supportive therapies.

Intraoperative electron beam radiotherapy and perioperative high-dose-rate brachytherapy in previously irradiated oligorecurrent gynecological cancer: clinical outcome analysis.

BACKGROUND: Pelvic recurrences from previously irradiated gynecological cancer lack solid evidence for recommendation on salvage. METHODS: A total of 58 patients were included in this clinical analysis. Salvage surgery was performed for locoregional relapse within previously irradiated pelvic area after initial surgery and adjuvant radiotherapy or radical external beam radiotherapy. The primary tumor diagnosis included cervical cancer (n = 47, 81%), uterine cancer (n = 4, 7%), and other types (n = 7, 12%). Thirty-three patients received adjuvant IOERT (1984-2000) at a median dose of 15 Gy (range 10-20 Gy) and 25 patients received adjuvant PHDRB (2001-2016) at a median dose of 32 Gy (range 24-40 Gy) in 6, 8, or 10 b.i.d. fractions. RESULTS: The median follow-up was 5.6 years (range 0.5-14.2 years). Twenty-nine (50.0%) patients had positive surgical margins. Grade ≥ 3 toxic events were recorded in 34 (58.6%) patients. The local control rate at 2 years was 51% and remained stable up to 14 years. Disease-free survival rates at 2, 5, and 10 years were 17.2, 15.5, and 15.5%, respectively. Overall survival rates at 2, 5, and 10 years were 58.1, 17.8, and 17.8%, respectively. CONCLUSIONS: IOERT and PHDRB account for an effective salvage in oligorecurrent gynecological tumors. Patients with previous pelvic radiation suitable for salvage surgery and at risk of inadequate margins could benefit from adjuvant reirradiation in form of IOERT or PHDRB. However, the rate of severe grade ≥ 3 toxicity associated with the entire treatment program is relevant and needs to be closely counterbalanced against the expected therapeutic gain.

[Radiotherapy in breast cancer: standards and new directions, accelerated partial breast irradiation]. / Tratamiento radioterápico del cáncer mama: estándares y nuevas tendencias. Irradiación parcial acelerada de la mama.

Radiotherapy as a part of the breast cancer treatment has evolved in the last decades. Post-mastectomy radiotherapy produces a substantial reduction in the risk of local recurrence as well as a moderate, but definitive reduction in long-term breast cancer mortality in women at high risk of locoregional failure. Whole-breast irradiation, as part of breast-conservation therapy, has well-established results with good cosmesis, and low toxicity. Results from the BCT trials suggest that the risk for ipsilateral breast cancer recurrence resides within close proximity to the original tumor site. This has led investigators to consider the role of an accelerated and more tumor bed-focused course of radiotherapy. Accelerated partial-breast irradiation (APBI) is a collection of radiotherapy techniques that deliver higher daily doses of radiation to the surgical cavity with margin over a shorter time than whole breast irradiation (from 6-6.5 weeks to 1 week). Early results of this approach have demonstrated excellent local control, minimal acute toxicity, and are more convenient for the patient. Phase III randomized clinical trials are currently underway to assess local control, acute and chronic toxicities. APBI extend the choise of breast conservation.

Predictive factors for radiation-induced pulmonary toxicity after three-dimensional conformal chemoradiation in locally advanced non-small-cell lung cancer.

BACKGROUND AND PURPOSE: Radiation pneumonitis (RP) is a restricting complication of non-small-cell lung cancer irradiation. Three-dimensional conformal radiotherapy (3D-CRT) represents an advance because exposure of normal tissues is minimised. This study tries to identify prognostic factors associated with severe RP. MATERIALS AND METHODS: Eighty patients with stage IIIA (20%) and IIIB (80%) NSCLC treated with cisplatin- based induction chemotherapy followed by concurrent chemotherapy and hyperfractionated 3D-CRT (median dose: 72.4 Gy, range: 54.1-85.9) were retrospectively evaluated. Acute and late RP were scored using RTOG glossary. Potential predictive factors evaluated included clinical, therapeutic and dosimetric factors. The lungs were defined as a whole organ. Univariate and multivariate analyses were performed. RESULTS: Early and late RP grade>or=3 were observed in two patients (2%) and 10 patients (12%), respectively. Five patients (6%) died of pulmonary toxicity, 3 of whom had pre-existing chronic obstructive pulmonary disease (COPD). Median time to occurrence of late RP was 4.5 months (range: 3-8). Multivariate analysis showed that COPD (OR=10.1, p=0.01) and NTCPkwa>30% (OR=10.5, p=0.007) were independently associated with late grade>or=3 RP. Incidence of RP>or=3 grade for patients with COPD and/or NTCPkwa>30% was 25% vs. 4% for patients without COPD and NTCPkwa<30% (p=0.01). Risk of severe RP was higher for patients with COPD and/or NTCPkwa>30% (OR=7.3; CI 95%=1.4-37.3, p=0.016). CONCLUSIONS: COPD and NTCP are predictive of severe RP. Careful medical evaluation and meticulous treatment planning are of paramount importance to decrease the incidence of severe RP.

Stereotactic body radiation therapy (SBRT) delays the emergence of castration resistance in patients with oligometastatic prostate cancer.

PURPOSE: To investigate whether bon e metastases-directed stereotactic body radiation therapy (SBRT) delays the emergence of castration resistance in patients with oligometastatic prostate cancer (OPC). METHODS AND MATERIAL: OPC is usually managed with androgen deprivation therapy (ADT). Migration to castration-resistant prostate cancer will inevitably occur in the majority of these patients. There are several strategies aimed to delay the emergence of castration resistance including intermittent ADT, second generation antiandrogens (abiraterone, enzalutamide) or metastases-directed SBRT. The present report describes two cases of patients with OPC that received SBRT 24 Gy/3Rx to the solitary bony lesion after ADT failure. RESULTS: Both cases showed complete and durable biochemical response for 13 and 17 months, respectively. CONCLUSIONS: SBRT can be used to delay the emergence of castration resistance and the need for systemic therapy when used after ADT failure.

Innovation in the management of soft tissue sarcomas in infants and young children: high-dose-rate brachytherapy.

PURPOSE: Conventional low-dose-rate (LDR) brachytherapy is effective in treating childhood sarcomas, but often not practical (due to the associated radiation hazards) in the young children who require continuous observation and sedation. Fractionated high-dose-rate brachytherapy (HDR) was used to deliver adequate tumoricidal radiation while preserving bone and organ growth in children. MATERIALS AND METHODS: Twelve children with diverse sarcomas were treated with fractionated HDR. The median age at diagnosis was 18 months (range, 1 to 42). Nine patients had rhabdomyosarcoma and three had other soft tissue sarcoma (STS) variants. Ten patients had microscopic residual disease at the time of brachytherapy. All patients were treated with appropriate chemotherapy and surgery. HDR was delivered in 3-Gy fractions twice a day to a total dose of 36 Gy in 8 days. External-beam radiation therapy (EBRT) was avoided. Patients were monitored for a median of 61 months (range, 30 to 78). RESULTS: One patient developed local recurrence and distant metastases to the lungs. The 6-year actuarial local control and overall survival rates were 91% and 81%, respectively. Brachytherapy-related morbidity occurred in 50% of patients. The morbidity was mild to moderate in 42% of patients and consisted primarily of acute skin and mucosal reaction. One patient experienced severe (grade III to IV) toxicity. Another child, treated to the tongue, had delayed dentition only in the teeth adjacent to the brachytherapy site. The other children have exhibited only minimal or none of the bone growth retardation expected with EBRT. CONCLUSION: The combination of conservative surgery, chemotherapy, and exclusive HDR to postchemotherapy tumor volume with a modest margin, avoiding EBRT, provided disease control in carefully selected young children, while preserving bone growth and organ function. The short duration of therapy and small volume irradiated allowed chemotherapy to be resumed shortly after brachytherapy. The use of HDR challenges the present philosophy of radiotherapy treatment volume, which holds that the prechemotherapy tumor volume should be treated with an acceptable margin. Brachytherapy should be included in multicentric clinical trials in young children.

Polymorphisms of the repeated sequences in the enhancer region of the thymidylate synthase gene promoter may predict downstaging after preoperative chemoradiation in rectal cancer.

PURPOSE: Thymidylate synthase (TS) is an important target enzyme for the fluoropyrimidines. TS gene promoter possesses regulatory tandemly repeated (TR) sequences that are polymorphic in humans, depending on ethnic factors. These polymorphisms have been reported to influence TS expression. TS expression levels affect tumor downstaging after preoperative fluoruracil (5-FU)-based chemoradiation. Tumor downstaging correlates with improved local control and disease-free survival. The aim of this study is to correlate TR polymorphisms with downstaging and disease-free survival. PATIENTS AND METHODS: Sixty-five patients with rectal cancer underwent tumor resection after preoperative 5-FU-based chemoradiation. Tumor downstaging was evaluated by comparing the pretreatment T stage with the pathologic stage observed in the surgical specimen. TS polymorphism genotype was determined by polymerase chain reaction amplification of the corresponding TS promoter region, and products of amplification were electrophoresed, obtaining products of 220 bp (2/2), 248 bp (3/3), or both (2/3). The TS polymorphism genotype results were subsequently compared with the downstaging observed and with disease-free survival. RESULTS: Patients who were homozygous for triple TR (3/3) had a lower probability of downstaging than patients who were homozygous with double TR or heterozygous patients (2/2 and 2/3): 22% versus 60% (P =.036; logistic regression). Furthermore, a trend toward improved 3-year disease-free survival was detected in the 2/2 and 2/3 groups, compared with that in the 3/3 group (81% v 41%; P =.17). CONCLUSION: This preliminary study suggests that TS repetitive-sequence polymorphisms are predictive for tumor downstaging. TR sequences in TS promoter may be useful as a novel means of predicting response to preoperative 5-FU-based chemoradiation.

125Iodine brachytherapy for colorectal adenocarcinoma recurrent in the pelvis and paraortics.

PURPOSE: To evaluate the results of 125I brachytherapy in colorectal cancers recurrent in the pelvis and paraortics. METHODS AND MATERIALS: From September 1989 to January 1997, 29 patients with colorectal adenocarcinoma recurrent in the pelvis or the paraortic nodes were treated intraoperatively with permanent 125iodine seed implantation at the James Cancer Center of The Ohio State University (OSU). All patients had undergone prior surgery; 72% had prior EBRT. The implanted residual tumor volume was microscopic in 38% and gross in 62%. The implanted area (median 25 cc) received a median minimal peripheral dose of 140 Gy to total decay. An omental pedicle was used to minimize irradiation of the bowel. Five patients received additional postimplant EBRT (20-50 Gy; median 30 Gy). RESULTS: The 1-, 2-, and 4-year actuarial local-regional control rates were 38%, 17%, and 17%, respectively, with a median time to local failure of 11 months (95% CI 10-12 months). The first manifestation of disease progression in 52 % of the patients was local-regional. In addition, 22 patients (75%) developed distant metastases. The 1-, 2-, and 4-year actuarial overall survival rates were 70%, 35%, and 21%, (median = 18 months; 95% CI: 14-22 months). Overall survival was better for patients smaller volume implants (p = 0.007), with a lower total activity implanted (p = 0.0003), with a smaller number of implanted sites (p = 0.004), and with microscopic residual disease (p = 0.01). Patients receiving additional EBRT also had a better prognosis (p = 0.005). Local tumor progression was the cause of death in 34% of the patients who have died at the time of this report and 56% died of distant metastases. Of the patients, 13 (45%) experienced 15 toxic events, including 3 patients (10%) with enteric fistula. Neuropathy was not observed. CONCLUSIONS: 125I brachytherapy can be successfully used for salvage in patients with recurrent colorectal cancer. Patients with isolated, microscopic, or minimal gross residual disease requiring small-volume implants and those receiving additional EBRT have a better prognosis. Postimplant EBRT is now routinely added, even for previously irradiated patients, in an attempt to improve local control. Compared to IOERT and IOHDR, 125I brachytherapy is not associated with clinical neuropathy, probably due to the continuous low dose rate irradiation delivered by the 125I seeds.

Pulmonary embolization of permanently implanted radioactive palladium-103 seeds for carcinoma of the prostate.

PURPOSE: It has been reported that permanently implanted iodine-125 seeds can embolize to the lungs. There is little data on the embolization of palladium-103 seeds. The purpose of this study is to collect and evaluate data on the embolization of Pd-103 seeds. METHODS AND MATERIALS: The records of 112 patients implanted with Pd-103 for carcinoma of the prostate were reviewed to systemically study the incidence and dynamics of pulmonary embolism of Pd-103 seeds. Five patients had no postoperative chest radiograph and were thus excluded, leaving 107 patients for review. RESULTS: Chest radiographs of 19 of the 107 patients showed embolized seeds in the lungs (18%). Two patients had three seeds each, nine patients had two seeds each; and in the remaining eight patients, a single seed migrated to the lungs. The seeds migrated mainly (84%) to the lower lobes. None of the eight patients who had their first postoperative chest radiograph on the day of the implant showed any embolized seeds. The embolized seed appeared only on subsequent chest radiographs taken 27 to 40 days later. Ten of the other 11 patients who had their first radiograph 1 to 97 days after brachytherapy had embolized seeds on their first chest radiograph. In the other patient, the embolized seed appeared only on a subsequent chest radiograph taken after 127 days. There were no clinical pulmonary or cardiac effects evident on routine follow-up of these patients with pulmonary embolized seeds. CONCLUSION: Embolization of Pd-103 seeds to the lungs after implantation for carcinoma of the prostate is an unusual event. In this study only 0.3% of the seeds implanted migrated to the lungs. Although it was previously thought that pulmonary seed migration mainly occurred on the day of brachytherapy, our experience shows that seeds usually migrated to the lungs after the day of the implant. There were no clinical pulmonary or cardiac effects attributable to embolized seeds in the lungs on routine follow-up.

Radioimmunoguided-intraoperative radiation therapy in colorectal carcinoma: a new technique to precisely define the clinical target volume.

PURPOSE: The clinical target volume (CTV) to be irradiated by intraoperative radiation therapy (IORT) after resection is generally based on the surgeon's estimation of close margins. We have developed a new technique, radioimmunoguided-intraoperative radiation therapy (RIG-IORT), that uses an intraoperative hand-held gamma-detecting probe to define areas of residual microscopic disease containing radiolabeled monoclonal antibodies to tumor associated antigen, to more precisely delineate the CTV for IORT. METHODS AND MATERIALS: Patients were injected i.v. with 2 mCi 125I- radiolabeled CC49 antibody approximately 3 weeks before surgery. They then underwent radioimmunoguided surgery (RIGS) with maximal resection of tumor. A hand-held gamma-detecting probe (Neoprobe 1000) was used intraoperatively to detect and resect areas of high radioactivity, representing tumor. Areas with persistently high probe counts after resection were the areas of occult residual disease, and represented the CTV to be irradiated. The IORT was given with either 6-9 MeV electron beam from a dedicated linear accelerator, or with high-dose-rate brachytherapy from a remote afterloader. If all RIGS-positive tissue had been resected, or if widely disseminated disease remained, the patient was not considered for IORT. RESULT: This technique was used in 31 patients with colorectal adenocarcinoma recurrent into the pelvis (n = 23) or paraortic nodes (n = 8). The CTV for IORT was delineated by increased RIGS count in 13 of 19 patients (68%) with microscopic residual, and in 11 of 12 patients (92%) with gross residual. In the other 7 patients, the tumor area did not accumulate the radiolabeled antibody; therefore, these tumor beds were irradiated based on the surgeon's estimation of close margins. Hence, overall, the RIG-IORT technique was used to define the tumor bed for IORT in 24 of 31 patients (77%). This technical report focuses on the development of the RIG-IORT technique and does not address the outcome results of the treated patients. CONCLUSION: A new technique, RIG-IORT, which uses radiolabeled monoclonal antibodies to precisely determine the CTV for IORT, is described. Whether the use of this technique will lead to improved tumor control will only be known upon the outcome analysis of RIG-IORT-treated patients compared with those obtained using traditional IORT techniques.

Intraoperative electron beam radiotherapy for previously irradiated advanced head and neck malignancies.

PURPOSE: This is a retrospective review to evaluate the role of surgery and intraoperative electron beam radiotherapy (IOERT) in the treatment of patients with previously irradiated advanced head and neck cancers. METHODS AND MATERIALS: Between January 1992 and March 1997, 38 patients (31 males, 7 females; median age of 62 years) with recurrent head and neck cancer were treated with maximal resection and IOERT at the Ohio State University (OSU). All had been previously treated with full-course radiotherapy (median 65.1 Gy, range 50-74.4 Gy). Twenty-nine patients (76%) had previously undergone one or more surgical procedures. After maximal surgery the tumor bed was treated with IOERT (single field in 36 patients and 2 fields in 2 patients), most commonly with 6 MeV electrons (87%). The dose administered (at 90% isodose line) was 15 Gy for close or microscopically positive margins in 34 patients and 20 Gy for gross disease in 1 patient. Further external beam radiation therapy (EBRT) was not given. RESULTS: After a median follow-up of 30 months (range 8-39 months), 24 of the 38 patients (66%) recurred within the IOERT field. Median time to IOERT failure was 6 months (95% CI: 4.3-7.7). The 6-month, 1-, and 2-year control rates within the IOERT volume were 41%, 19%, and 13%, respectively. Thirty of the 38 patients (79%) recurred in locoregional areas. Median time to locoregional failure was 4 months (95% CI: 3.3-4.7). The 6-month, 1-, and 2-year locoregional control rates were 33%, 11%, and 4%, respectively. Distant metastases occurred in 7 patients, 5 in association with IOERT failure and 2 with locoregional failure. Median overall survival was 7 months (95% CI: 4.7-9.3). The 6-month, 1-, 2-, and 3-year actuarial survival rates were 51%, 21%, 21%, and 8%, respectively. Major treatment-related complications occurred in 6 patients (16%). CONCLUSION: IOERT alone, at the dose used, is not sufficient for control of recurrent, previously irradiated head and neck cancers. Since higher IOERT doses are associated with high morbidity, we are currently evaluating the addition of limited EBRT dose and/or brachytherapy to improve the local control of these poor prognostic recurrent tumors, with acceptable morbidity.

Long-term normal tissue effects of intraoperative electron radiation therapy (IOERT): late sequelae, tumor recurrence, and second malignancies.

PURPOSE: To evaluate long-term survivors treated with intraoperative electron radiation therapy (IOERT) as a component, with particular emphasis on analyzing late normal tissue toxicity, second malignancies, and patterns of delayed tumor recurrence. METHODS AND MATERIALS: From September 1984 to December 1991, 739 patients were treated with IOERT. One hundred ninety-five patients were alive at least 5 years after IOERT (26%). Patient information regarding late complications related symptoms, incidence of second tumors, and delayed relapses were analyzed. Normal tissue changes were categorized by a modified LENT/SOMA scale (Grade 0-1, Grade 2, and Grade 3-4). Risk of late toxicity was grouped by type and number of cancer treatment modalities employed in each patient: surgery + IOERT alone (17 patients, 9%); IOERT + external radiotherapy +/- chemosensibilization (90 patients, 46%); IOERT +/- external radiotherapy +/- neoadjuvant chemotherapy (+/- previous radiotherapy) (88 patients, 45%). Biologic effective doses (BED) were calculated for alpha/beta = 3.5 for late fibrosis. RESULTS: With a mean follow-up time of the surviving patients of 94 months (range: 55-162 months), 99 patients (51%) had Grade 0-1 toxicity, 52 (27%) had Grade 2, and 44 patients (23%) presented Grade 3-4 late normal tissue complications. Risk groups by treatment intensity did correlate with severity of observed toxicity (p < 0.001). BED estimations did not correlate with late normal tissue damage. The tumor type with higher toxicity scores was bone sarcoma (28/46, 60%), in which the estimated BED = 100.5 Gy. Peripheral neuropathy was the dominant IOERT-specific toxicity present in 24 patients (12%). Second malignancies were identified in 8 patients (4%), none inside the IOERT field (3 questionable to be marginal to the external beam radiotherapy volume). In 36 patients (18%), recurrence of the originally treated tumor was detected, including 11 (7%) local relapses. CONCLUSIONS: The incidence of late normal tissue complications (50%) and severity (23%) is significant in a cohort of patients surviving more the 5 years after IOERT. The understanding of the contribution of IOERT to late tissue damage requires specific analysis. Peripheral neuropathy is a characteristic finding in IOERT trials. Second malignancies inside the IOERT field were not identified during the study period. The risk of recurrences, including local failures, requires an intensive follow-up of long-term survivors from IOERT trials.

The use of fluoroscopy to guide needle placement in interstitial gynecological brachytherapy.

PURPOSE: Interstitial brachytherapy is generally performed for gynecological malignancies with extensive parametrial involvement, by inserting the needles through a transperineal template. Often, the implanted needles are not parallel, and the multiple sources can be difficult to identify on localization radiographs, especially if obtained with a portable X-ray unit. We have used fluoroscopy to guide the needles for interstitial brachytherapy to treat various gynecological malignancies. Because the resultant needles are parallel, dosimetry can be performed based on the template hole positions used, rather than identifying individual sources. This report focuses on the technique; the outcome of patients implanted with this technique will be reported separately. METHODS: Seventy-one patients were implanted transperineally with 192iridium using a Syed template under fluoroscopic guidance, from September 1989 to May 1995, for bulky parametrial disease, narrow vagina, extensive vaginal involvement, recurrent disease after previous course of pelvic radiation therapy, or in cases in which the patient had previously undergone hysterectomy. 137Cesium was added in a central tandem in cases with a cervical os. Thirty patients were treated for primary cervical or vaginal carcinoma; 41 patients were treated for recurrent disease from endometrial or cervical cancers. The brachytherapy dose (prescribed to the periphery of the implant) was 40 to 55 Gy when used alone (15 patients) and 22-40 Gy when used as a boost to 34.2 to 59.4 Gy of pelvic external-beam radiotherapy (56 patients). The patients were followed for 6 to 63 months. RESULTS: In all cases, some of the needles had to be repositioned to improve the alignment. Hence, the use of fluoroscopy aided in achieving parallel placement of the needles in all implants as seen on anterior-posterior radiographs. Because the 192iridium sources were ordered beforehand based on the preplan, and the dosimetry was based on idealized geometry of the template hole positions, all patients were loaded on the same day of implant. CONCLUSION: Fluoroscopically guided perineal interstitial brachytherapy is a feasible technique for use in various gynecological malignancies. The use of fluoroscopic guidance helped to achieve parallel needle placement in all of our implants, but it required repositioning of some of the needles in all cases. The parallel positioning allowed the use of preplanned dosimetry, minimizing the delay in loading of the patients. The outcome of the patients treated using this technique is currently undergoing analysis and will be reported separately.

Simplified non-looping functional loop technique for HDR brachytherapy.

The loop technique has been employed in interstitial implantation of head and neck cancers for decades. However, cable-driven afterloading sources may be unable to negotiate the curve of the loop. The technique allows separate afterloading of each catheter ensuring a good dose distribution to the surface of the implanted structure.

Intraoperative radiotherapy in recurrent gynecological cancer.

A retrospective analysis to assess the feasibility and clinical tolerance of intraoperative radiotherapy (IORT) in the treatment of recurrent gynecologic cancer is reported. From February 1985 to September 1992, 26 patients with recurrent gynecologic tumors entered this trial. The clinical experience comprises two different categories of disease situations: tumors relapsing after full dose radiation therapy (group I) and recurrent disease to previous surgery (group II). Cervical carcinoma was the initial tumor site of involvement in 18 patients (69%). Treatment consisted in maximal surgical resection + IORT boost (10-25 Gy) to the high-risk areas for recurrence. Non previously irradiated patients also received external beam irradiation (EBRT) (+/- chemotherapy) pre- or postoperatively. IORT-related toxicity was one episode of motor neuropathy. Local control rates have been 33% and 77%, respectively in groups I and II. The 4-year actuarial overall survival in Group I is 7% and 6-year actuarial overall survival in Group II is 33%. The addition of IORT to surgical debulking achieves modest local control and long-term survival rates if tumor-free margins cannot be obtained in previously irradiated patients. Combined EBRT (+/- chemotherapy) maximal surgical resection plus IORT could render some long-term survivors among those surgical recurrent patients not candidates for radical surgery with curative intent.

Multiple cycles of dose-intensive chemotherapy with repeated stem cell support as induction treatment in metastatic breast cancer: a feasibility study.

The purpose of this trial was to study feasibility and tolerance of a dose-intensive multicyclic alternating induction chemotherapy with repeated stem cell support in a series of 43 metastatic breast cancer patients. Anthracycline-naive patients (n = 21) received cyclophosphamide 2.5 g/m(2) plus doxorubicin 80 mg/m(2) alternating every 14 days with paclitaxel 200-350 mg/m(2) plus cisplatin 120 mg/m(2). Patients who had previously received anthracyclines (n = 22) received cisplatin 120 mg/m(2) plus etoposide 600 mg/m(2) alternating with paclitaxel 200-350 mg/m(2) plus ifosfamide 8 g/m(2). Peripheral blood stem cells were infused after every course except the first, with a median CD34(+) dose of 2.1 x 10(6)/kg per cycle. Positive selection of CD34(+) cells was performed in good mobilizers. The median number of cycles administered was six (4-8), and the time interval between them was 17 days. Median summation dose intensities (SDI) actually administered for the CA-TP and PE-TI protocol were 4.95 and 4.69, respectively (87% of scheduled SDI). There were 15 complete (35%) and 21 partial responses (49%), for an overall response rate of 84% (95% CI, 73%-95%). Infection or neutropenic fever occurred in 50% of the cycles. There was one treatment-related death. After a median follow-up of 26 months, the median event-free-survival was 12 months (95% CI: 10-14) and overall survival was 31 months. These high dose-intensity induction treatments seem to be feasible with sequential stem cell support.

Use of brachytherapy to preserve function in children with soft-tissue sarcomas.

Pediatric soft-tissue sarcomas are managed with a multimodality treatment program that includes surgery, chemotherapy, and external-beam radiotherapy (teletherapy). The use of teletherapy in young children can result in significant long-term toxicities (especially growth retardation of bones and organs). Brachytherapy, if feasible, is an attractive alternative for the treatment of pediatric soft-tissue sarcomas, since it irradiates small volumes and, thus, may potentially minimize complications. Aggressive chemotherapy is used to achieve systemic control and tumor shrinkage, thereby facilitating conservative surgery and brachytherapy. The brachytherapy techniques used in children are similar to those employed in adults. Low-dose-rate (LDR) brachytherapy with manually afterloaded removable iridium-192 is commonly used, although it is associated with some radiation exposure hazards. Low-energy radionuclides (e.g., iodine-125) and remote afterloading technology have been used to reduce radiation exposure hazards. Brachytherapy, in conjunction with chemotherapy and surgery but without supplementary teletherapy, has produced good local control with acceptable late complications in selected patients with localized tumors. Brachytherapy can also be used as a boost to moderate dose external-beam radiotherapy for more extensive tumors. The use of newer modalities, such as high-dose-rate, pulsed-dose-rate, and intraoperative brachytherapy, has allowed brachytherapy to be given to younger children and infants, but the long-term morbidities of these modalities need to be established.

Intensification regimen 2 for advanced head and neck squamous cell carcinomas.

OBJECTIVE: To determine the feasibility, toxicity, and compliance of an intense treatment regimen for patients with advanced, previously untreated, resectable head and neck squamous cell carcinomas. DESIGN: Prospective, nonrandomized, controlled (phase 1 or 2) clinical trial; median time at risk, 25 months (range, 7 days to 36 months). SETTING: Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University, Columbus. PATIENTS: Forty-three patients (median age, 59 years; range, 32-76 years) with resectable, previously untreated stage III or IV squamous cell carcinomas of the oral cavity, oropharynx, or hypopharynx or stage II squamous cell carcinomas of the hypopharynx (referred sample of patients). INTERVENTIONS: Days 1 to 4, perioperative, slightly accelerated, hyperfractionated radiotherapy (9.1 Gy) to off cord fields; days 1 to 3, cisplatin, 30 mg/m2 per day; day 4, surgical resection and intraoperative radiotherapy boost (7.5 Gy); days 45 to 52, postoperative radiotherapy (40 Gy to the primary site and upper neck and 45 Gy to the supraclavicular areas); days 24, 45, and 66, paclitaxel, 135 mg/m2 per 24 hours, with routine granulocyte colony-stimulating factor support; and days 25 and 46, cisplatin, 100 mg/m2. MAIN OUTCOME MEASURES: Toxicity, compliance, local control, and distant metastatic rates. RESULTS: Patient compliance was 91% (39 of 43 patients), but protocol compliance was only 58% (25 of 43 patients), reflecting increased toxicity of the systemic regimen (2 [5%] of the 43 patients experienced grade 5 hematologic toxicity due to the regimen; 16 [37%], grade 4; and 10 [23%], grade 3). Local-regional control was 92% (23 of 25 patients), and the distant metastatic rate was 8% (2 of 25) in patients completing treatment per protocol. One patient had surgical salvage of a second primary tumor. CONCLUSIONS: Local control and patient compliance were encouraging, but systemic toxicity was unacceptable. Thus, the paclitaxel was changed to a weekly regimen.