Point vs. volumetric bladder and rectal doses in combined intracavitary-interstitial high-dose-rate brachytherapy: correlation and comparison with published Vienna applicator data.

PURPOSE: We correlated rectal and bladder point and volumetric dose data in patients treated for advanced cervix cancers with combined intracavitary-interstitial high-dose-rate (HDR) brachytherapy (BT). The results are compared with published Vienna applicator data. METHODS AND MATERIALS: We retrospectively analyzed 30 individual combined intracavitary plus interstitial implants from 10 patients treated with external beam radiation therapy (EBRT) followed by HDR BT for locally advanced cervix carcinoma. EBRT consisted of 45 Gy to the pelvis followed by 9-14.4 Gy boost to involved parametria. BT consisted of a total dose of 21 Gy delivered in 7 Gy fraction. For each implant, CT-image-based simulation and image-guided BT treatment planning was performed. Bladder and rectal doses were evaluated and analyzed using both International commission on Radiation Units and Measurements (ICRU) reference points and dose-volume histograms. The cumulative doses to the rectum and bladder were calculated by combining contributions from external beam therapy and BT. To facilitate comparison with published literature, the total doses were normalized to equivalent dose in 2-Gy fractions (EQD2) using the equation EQD2total = EQD2EBRT + EQD2BT. RESULTS: For the patient population considered, the mean ICRU bladder dose was 75 (+/-4) Gy3 compared to bladder D0.1 cc and D2 cc doses of 84 (+/-4) and 78 (+/-3) Gy3, respectively. The mean ICRU rectal dose was 73 (+/-4) Gy3 compared to rectal D0.1 cc and D2 cc doses of 79 (+/-5) and 74 (+/-4) Gy3, respectively. For rectum, the mean dose ratios (D0.1 cc/D(ICRU)) and (D2 cc/D(ICRU)) were 1.08 and 1.01, respectively, compared to Vienna applicator study mean dose ratios of 1.08 and 0.93, respectively. ICRU rectal dose correlated with volumetric rectal doses and best with volumetric D2 cc dose (rS = 0.91, p = 0.0003); however, ICRU bladder dose did not correlate with volumetric bladder dose. CONCLUSIONS: Our study findings reveal a strong correlation between ICRU rectal reference dose and volumetric rectal D2 cc dose in combined intracavitary-interstitial HDR brachytherapy. This surrogate rectal-dose relationship is valuable in establishing rectal tolerance dose levels in transitioning from traditional two-dimensional to image-based three-dimensional dose planning.

Adjuvant high dose rate brachytherapy (Ir-192) in the management of keloids which have recurred after surgical excision and external radiation.

We describe our experience with adjuvant high dose rate brachytherapy (Ir-192) (HDRB) in patients, who failed surgery and post-operative external radiation therapy. The salvage treatment consisted of excision of the keloid and wound closure followed by HDRB (15 Gy in three fractions given on three consecutive business days beginning the day of surgery). At the time of last follow up, 88% (15/17) of the keloids were without any evidence of recurrence.

Extended-field radiotherapy and high-dose-rate brachytherapy in carcinoma of the uterine cervix: clinical experience with and without concomitant chemotherapy.

BACKGROUND: It has long been recognized that many patients with locally advanced carcinoma of the cervix harbor occult paraaortic metastases. A randomized study demonstrated that elective paraaortic irradiation improved survival and reduced distant metastases. More recently, concomitant chemotherapy with pelvic irradiation has improved survival among patients with locally advanced carcinoma of the cervix. This has led to a reexamination of the role of extended-field irradiation. An important issue is the toxicity of concomitant chemotherapy and extended-field radiotherapy. The authors report a retrospective analysis of their experience with extended-field radiotherapy and high-dose-rate brachytherapy with or without concomitant chemotherapy. METHODS: The authors treated 54 women with biopsy-confirmed carcinoma of the cervix using extended-field radiotherapy and high-dose-rate brachytherapy with or without concomitant chemotherapy. The histology was squamous cell carcinoma in 49 patients (91%) and nonsquamous cell carcinoma in 5 patients (9%). The median size of the primary tumor was 7 cm (range, 3-10 cm). Each patient received 45 grays (Gy) of external beam radiotherapy to the pelvis and the paraaortic region, followed by a parametrial boost (9 Gy) in the patients with disease extension to the parametrium or the pelvic side wall(s). Each patient also underwent two applications of high-dose-rate brachytherapy, 1 week apart. The median dose delivered to Point A from each application was 9 Gy. Forty-four of the 54 patients (81%) received concomitant chemotherapy (cisplatin, 20 mg/m(2)/day for 5 days) during the first and the fourth weeks of external beam radiotherapy, and once after the second high-dose rate application. Chemotherapy was not assigned randomly. RESULTS: One of the 10 patients (10%) treated without chemotherapy experienced acute toxicity, whereas 41 of 44 patients (93%) who received chemotherapy suffered from acute toxicity, including hematologic toxicity, gastrointestinal toxicity, and deep venous thrombosis. During a median follow-up period of 28 months (range, 12-70 months), 6 of the 54 patients have died (11%). The actuarial rate of local control at 3 years is 100% among the patients treated without chemotherapy, compared with 85% among those receiving chemotherapy. No one failed in the paraaortic region. The actuarial rates of freedom from distant metastases are 90% and 95% among the patients treated without and with chemotherapy, respectively. The actuarial incidence of late toxicity is 10% among the patients treated without chemotherapy and 6% among those receiving chemotherapy. CONCLUSIONS: The regimen of extended-field radiotherapy with concomitant cisplatin and high-dose-rate brachytherapy produced substantial acute toxicity, but its long-term toxicity is low and the preliminary tumor control excellent, albeit with limited follow-up. Only prospective, randomized trials can evaluate whether these results are truly better than those of pelvic radiotherapy with concomitant chemotherapy, or those of other regimens of extended-field radiotherapy with concomitant chemotherapy. Cancer 2003;97:1781-8.

Radiation therapy for the salvage of unresectable subungual squamous cell carcinoma.

BACKGROUND: A case of subungual squamous cell carcinoma, which is a rare malignancy and has an elusive etiology, is reported. OBJECTIVE: To present radiation therapy as a viable treatment option to amputation for surgically unresectable subungual squamous cell cancer. METHODS: A 69-year-old man with a 16-year-old history of subungual squamous cell carcinoma of the left thumb was treated by external beam radiation therapy. In this case, bone invasion precluded the patient from successfully completing Moh's micrographic surgery. RESULTS: The treated thumb at 17 months after radiation therapy remained tumor free. CONCLUSION: Radiation therapy should be considered a treatment option for nail bed squamous cell carcinoma before considering amputation and perhaps as salvage for all unresectable lesions.

Cell transplantation after oxidative hepatic preconditioning with radiation and ischemia-reperfusion leads to extensive liver repopulation.

The inability of transplanted cells to proliferate in the normal liver hampers cell therapy. We considered that oxidative hepatic DNA damage would impair the survival of native cells and promote proliferation in transplanted cells. Dipeptidyl peptidase-deficient F344 rats were preconditioned with whole liver radiation and warm ischemia-reperfusion followed by intrasplenic transplantation of syngeneic F344 rat hepatocytes. The preconditioning was well tolerated, although serum aminotransferase levels rose transiently and hepatic injury was observed histologically, along with decreased catalase activity and 8-hydroxy adducts of guanine, indicating oxidative DNA damage. Transplanted cells did not proliferate in the liver over 3 months in control animals and animals preconditioned with ischemia-reperfusion alone. Animals treated with radiation alone showed some transplanted cell proliferation. In contrast, the liver of animals preconditioned with radiation plus ischemia-reperfusion was replaced virtually completely over 3 months. Transplanted cells integrated in the liver parenchyma and liver architecture were preserved normally. These findings offer a paradigm for repopulating the liver with transplanted cells. Progressive loss of cells experiencing oxidative DNA damage after radiation and ischemia-reperfusion injury could be of significance for epithelial renewal in additional organs.

Normal hepatocytes correct serum bilirubin after repopulation of Gunn rat liver subjected to irradiation/partial resection.

The treatment of inherited metabolic liver diseases by hepatocyte transplantation (HT) would be greatly facilitated if the transplanted normal hepatocytes could be induced to proliferate preferentially over the host liver cells. We hypothesized that preparative hepatic irradiation (HIR) should inhibit host hepatocyte proliferation in response to partial hepatectomy (PH). Normal nonirradiated hepatocytes transplanted in this setting should have a selective growth advantage over the host liver cells and should progressively repopulate the liver. To test this hypothesis, we transplanted 5 million hepatocytes from normal Wistar-Roman High Avoidance (RHA) rats into the livers of congeneic bilirubin-uridine 5'-diphosphoglucuronate glucuronosyltransferase (UGT1A1)-deficient jaundiced Gunn rats by intrasplenic injection after one of the following treatments: (1) 68% PH, (2) HIR (50 Gy), or (3) HIR + PH. In rats receiving either PH or HIR alone before HT, serum bilirubin concentrations declined by 25% to 30% in 28 weeks. In contrast, serum bilirubin levels were normalized completely in rats receiving HIR + PH before HT. Massive repopulation of the Gunn rat liver by the UGT1A1-positive Wistar-RHA hepatocytes was shown by UGT1A1 enzyme assay, immunoblot analysis, and immunohistochemical staining of the recipient liver. High-performance liquid chromatography analysis of the bile collected from Gunn rats 5 months after PH, HIR, and HT showed normalization of the pigment profile, with bilirubin diglucuronide and monoglucuronide as the predominant pigments. In conclusion, a preparative regimen of HIR + PH results in massive repopulation of the liver with functionally normal transplanted hepatocytes, resulting in complete correction of a metabolic deficiency. Noninvasive strategies to replace PH for providing proliferative stimuli to the transplanted cells should make this regimen valuable in augmenting the effects of HT for the treatment of liver diseases.