Four-dimensional computed tomography-based respiratory-gated whole-abdominal intensity-modulated radiation therapy for ovarian cancer: a feasibility study.

This study assesses the feasibility and implementation of respiratory-gated whole-abdominal intensity-modulated radiation therapy (RG-WAIMRT). Three patients were treated with RG-WAIMRT. The planning target volume (PTV1) included the entire peritoneal cavity and a pelvic boost field was created (PTV2). The dose prescribed was 30 Gy to PTV1 and 14.4 Gy to PTV2. For comparison, a conventional three-dimensional (3D) plan was generated for each patient. In the WAIMRT plan, an average of 90% of PTV1 received 30 Gy compared to 70% for the conventional 3D plan. The percent volume receiving 30 Gy (V(30)) for liver averaged 54% (WAIMRT) vs 43% (3D). The percent volume receiving 20 Gy (V(20)) for kidneys averaged 19% vs 0%, and the mean V(20) for bone marrow was 74% vs 83%, respectively. Major acute toxicities were anemia (grade 2: 1/3), leukopenia (grade 3: 2/3 patients), and thrombocytopenia (grade 2: 1/3 patients, grade 3: 1/3 patients). One patient could not complete the whole-abdomen field after 19.5 Gy because of persistent nausea. No major subacute toxicity has been reported. WAIMRT demonstrated superior target coverage and reduced dose to bone marrow, with a slightly increased dose to liver and kidneys. WAIMRT is a novel and feasible technique for ovarian cancer treatment.

Villoglandular adenocarcinoma of the cervix recurrent in an episiotomy scar: a case report in a 32-year-old female.

Cervical cancer during pregnancy is rare, occurring in approximately 3% of cervical cancer cases. Considerable controversy exists as to the long-term prognosis of patients diagnosed during pregnancy. A 32-year-old female presented with vaginal spotting in April 1998. A prenatal smear in December 1996 revealed atypical glandular cells of undetermined significance. A sterile speculum exam in April 1997 at 31-week gestational age revealed a polyp on the anterior lip of the cervix, pathology consistent with a well-differentiated villoglandular adenocarcinoma. In August 1997, the patient underwent a radical hysterectomy with pelvic/para-aortic lymphadenectomy. In April 2001, she represented with nodular perineal mass in the episiotomy incision. She received preoperative radiotherapy with a near-complete response and remained without disease for >10 months. It appears that a less radical procedure can offer significant therapeutic value. Preoperative radiotherapy proved effective at achieving a near-complete response. The patient underwent a wide local excision of the perineal area with resultant negative margins.

Conventional 3D conformal versus intensity-modulated radiotherapy for the adjuvant treatment of gynecologic malignancies: a comparative dosimetric study of dose-volume histograms.

OBJECTIVE: The goals of this study were to evaluate the feasibility of pelvic intensity-modulated radiotherapy (IMRT) in the adjuvant treatment of gynecologic malignancies and to compare the dose-volume histograms (DVHs) and determine the potential impact on acute and long-term toxicity based on the dose to target and nontarget tissues for both planning techniques. METHODS: Ten consecutive patients referred for adjuvant radiotherapy for gynecologic malignancies at the University of Pittsburgh School of Medicine and Magee-Womens Hospital were selected for CT-based treatment planning using the ADAC 3D version 4.2g and the NOMOS Corvus IMRT version 4.0. Normal tissues and critical structures were contoured on axial CT slices by both systems in conjunction with a gynecologic radiologist. These regions included internal, external, and common iliac nodal groups, rectum, upper 4 cm of vagina, bladder, and small bowel. Conventional treatment planning included 3D four-field box using 18-MV photons designed to treat a volume from the L(5)/S(1) border superiorly to the bottom of the ischial tuberosity on the AP/PA field and shaped blocks on the lateral fields to minimize the dose to the rectum and small bowel. A seven-field technique using 6-MV photons was used for IMRT. Restraints on small bowel for IMRT were set at 23.0 Gy +/- 5% and 35.0 Gy+/- 5% for the rectum and 37.5 Gy +/- 5% for the bladder while simultaneously delivering full dose (45.0 Gy) to the intrapelvic nodal groups in 1.8-Gy daily fractions. The dose-volume histograms where then compared for both treatment delivery systems. RESULTS: The volume of each organ of interest (small bowel, bladder, and rectum) receiving doses in excess of 30 Gy was compared in the 3D and IMRT treatment plans. The mean volume of small bowel receiving doses in excess of 30 Gy was reduced by 52% with IMRT compared with 3D. A similar advantage was noted for the rectum (66% reduction) and the bladder (36% reduction). The nodal regions at risk and the upper vagina all received the prescribed dose of 45.0 Gy. CONCLUSIONS: Intensity-modulated radiotherapy appears to offer several advantages over conventional 3D radiotherapy (3D CRT) planning for adjuvant radiotherapy for gynecologic malignancies. These include a significant reduction in treatment volume for bladder, rectum, and small bowel. It is anticipated that this reduction in volume of normal tissue irradiated would translate into overall reduction in acute and potentially late treatment-related toxicity. Prospective trials are necessary to better evaluate the advantages in a larger group of patients.

Concurrent sequencing of full-dose CMF chemotherapy and radiation therapy in early breast cancer has no effect on treatment delivery.

With the increasing use of breast-conserving therapy plus systemic chemotherapy for the treatment of early breast cancer, the optimal sequencing of radiation therapy and chemotherapy remains controversial. Sequencing of therapy may influence not only treatment delivery, but control rates, complications and cosmesis. The aim of this study was to evaluate whether concurrent sequencing of standard doses of CMF (cyclophosphamide, methotrexate and 5-fluorouracil) and adjuvant radiation therapy for early breast cancer impacted on optimum treatment delivery. As both an intravenous (i.v.) 3-week regimen and classic (standard) CMF were utilised in this study, both types of CMF were compared. The effect of sequencing on complications and treatment delays were also assessed. 116 patients treated with CMF chemotherapy and adjuvant tangent breast radiation were studied. 73 patients were treated prospectively with concurrent therapy and were retrospectively compared with a matched group of 40 patients treated with sequential or sandwich therapy. All patients had stage 1 or 2 cancers. There were no planned dose reductions introduced for either treatment modality. Concurrent sequencing had no impact on the ability to deliver optimum radiation or chemotherapy doses. There was no significant difference in acute Radiation Therapy Oncology Group (RTOG) skin reactions or complications between the two groups. Although small, there was a significant delay (1.32 days (0-15 versus 0.36 (0-7)) in the concurrent group (P=0.03) in the delivery of radiation therapy. Sequencing had no significant effect on haematological parameters. 'Standard' CMF had a more profound effect on treatment delivery than i.v. CMF (Radiation delay 2.2 days versus 0.26, P=0.002, % chemotherapy delivered 93% versus 99% P=0.000004). At a mean follow-up of 2.6 years, there was no difference in the cosmetic scores between the two groups. Both local and distant control rates were excellent. This study has shown that standard radiation therapy can be delivered safely concurrently with CMF chemotherapy. Whether this approach may lead to better control rates in the future needs further study.

Lumpectomy and breast irradiation for breast cancer arising after previous radiotherapy for Hodgkin's disease or lymphoma.

Twelve women treated with radiotherapy with or without chemotherapy for Hodgkin's disease (11 patients) and non-Hodgkin's lymphoma (1 patient) and in whom breast cancer subsequently developed 10 to 29 years later were treated with lumpectomy and breast irradiation. 5,000 cGy/25-30 fractions to the whole breast and 900 cGy to 1.000 cGy/5 boost to the operative area. Six also received adjuvant chemotherapy for breast cancer. Breast irradiation was well tolerated without any unusual acute or chronic sequelae. All women had a good to excellent cosmetic result. Ten women are alive and well 1 to 174 months (median: 46) from completion of breast irradiation. Two women died with distant metastasis but without local recurrence. Breast conservation therapy with radiotherapy is not contraindicated in the woman who has previously been treated with radiotherapy for Hodgkin's disease or lymphoma.

Point dose variations with time during traditional brachytherapy for cervical carcinoma.

In traditional brachytherapy for carcinoma of the cervix, doses are often prescribed to specifically chosen points (A and B) and the normal tissue tolerance calculated at specific reference points in the bladder and rectum. These tolerance doses are often used to modify the brachytherapy treatment plan. It is inherently assumed that the position of the brachytherapy applicator does not change in relation to the relevant anatomical structures over the time-course of an implant. To assess the accuracy of this assumption, 2 sets of localization films were obtained for each implant in 28 patients, 1 prior to loading and another after the removal of the radioactive sources. Significant applicator movement and, consequently, significant dose variations were ob: served. Therefore, isolated one-time dose measurements to normal critical structures should not be used as the sole basis for making therapeutic decisions. The magnitude of dose variations and their clinical significant are discussed.

A phase I/II study of hypofractionated whole abdominal radiation therapy in patients with chemoresistant ovarian carcinoma: Karnofsky score determines treatment outcome.

PURPOSE: Radiation therapy can provide useful palliation in chemorefractory ovarian cancer patients. The purpose of this study was to prospectively study the palliative effect of a hypofractionated radiation treatment regimen. Change in quality-of-life scores (Functional Assessment of Cancer Therapy [FACT], Karnofsky scale), pain score, and tolerance to therapy were also assessed. METHODS AND MATERIALS: A single-institution Phase I/II trial was initiated in patients with chemoresistant recurrent or progressive ovarian cancer. All patients had symptomatic and measurable intra-abdominal disease. Patients were treated with a single radiation fraction (700 cGy) or two fractions (300 cGy twice a day) to the whole abdomen over 1 day. Quality-of-life scale (FACT G version 2) was assessed at baseline and 1 and 3 months following treatment. Karnofsky scale and pain score were also evaluated in the same time frame. RESULTS: Sixteen patients were prospectively entered into this protocol between February 1996 and September 1998. Twelve patients received a single 700 cGy fraction and four 300 cGy twice a day. All were heavily pretreated and 9 (56%) had a poor performance status prior to treatment. Symptoms needing palliation included pain (14), ascites (10), and bleeding (2). Symptomatic improvement occurred in all patients with pain (5 complete response [CR] and 7 partial response [PR], all patients with bleeding (CR 2), and two (20%) with ascites. Five patients (31%) had a reduction in lesion size documented radiologically in three. The mean duration of response was 22 weeks in patients with a Karnofsky score >70. Thirteen patients developed transient nausea and vomiting which resolved in 48 hours in all. All patients developed a transient lymphopenia. Thirteen patients completed a follow-up quality-of-life scale. There was an improvement in the physical and functional components of the scale in patients with Karnofsky score of 90-100. There was no improvement in quality of life in patients with Karnofsky score <90 despite symptomatic response. Median survival was 3 months from the date of treatment. CONCLUSION: Hypofractionated radiation therapy is an effective palliative treatment for end-stage ovarian cancer patients. Karnofsky score can help determine the duration of response and survival for this high-risk population.

Inhibition of peridural fibrosis after laminectomy using low-dose external beam radiation in a dog model.

OBJECTIVE: Clinical studies have demonstrated a significant association between the presence of extensive postlumbar discectomy peridural scar formation and the recurrence of low back and radicular pain. Low-dose perioperative radiation therapy has previously been demonstrated to inhibit peridural fibrosis after laminectomy in a rat model. The current study was designed to measure the effect of low-dose radiation on postlaminectomy peridural fibrosis development in a larger animal model. METHODS: Three dogs underwent a total of 12 lumbar hemilaminectomies. For each animal, two levels received 1) external beam radiation 24 hours before surgery, 2) surgery alone, or 3) radiation alone. Radiation was administered in a single fraction of 700 cGy using computed tomographic guidance for dosimetry planning. The isodose distribution was such that the dose conformed to the posterior epidural space with minimal exit dose to normal tissue. Port films were used to confirm the correct levels. Gadolinium-enhanced magnetic resonance imaging (MRI) of the lumbar spines was obtained before the animals were killed 12 weeks after surgery. The spines were harvested, and axial sections through the laminectomy defect were stained with hematoxylin and eosin and Masson's trichrome. All specimens were evaluated for extent of fibrosis along the dura, density of fibrosis, nerve root entrapment, and sublaminar fibrosis. RESULTS: There were no complications from the surgery, and no new neurological deficits were noted. There was a statistically significant difference between the irradiated and nonirradiated groups regarding the extent of fibrosis (P = 0.001) and the density of fibroblasts (P = 0.001). There was also a marked difference in nerve root entrapment (P = 0.182) and the presence of sublaminar fibrosis (P = 0.061) between the treatment and control groups. MRI revealed less gadolinium enhancement at the irradiated levels compared with the nonirradiated levels, confirming the usefulness of MRI in predicting the degree of epidural fibrosis. CONCLUSION: Low-dose external beam radiation therapy administered 24 hours before laminectomy in a dog model significantly decreased the extent and density of peridural fibrosis as well as nerve root entrapment and sublaminar fibrosis. This treatment strategy may be efficacious in patients with recurrent radicular pain after lumbar discectomy that is thought to be secondary to peridural fibrosis on the basis of gadolinium-enhanced MRI studies, and who might benefit from reoperation for nerve root decompression.

Pathologic stage III endometrial cancer treated with adjuvant radiation therapy.

This study was undertaken to evaluate the outcome of pathologic stage III endometrial carcinoma treated with adjuvant radiation therapy (RT). A retrospective review was performed on 32 patients receiving adjuvant RT following abdominal hysterectomy for stage III endometrial carcinoma (19 IIIA, 2 IIIB, 11 IIIC) between 1980 and 1996. Papillary-serous and clear cell adenocarcinomas were excluded. Pathologic nodal sampling was performed on 25 patients (78%). All patients received postoperative external beam RT to the pelvis and 25 of 32 received an additional brachytherapy boost to the vaginal apex. Three patients with involved para-aortic nodes received extended field RT. Mean follow up was 70 mos. Twenty-four patients remain disease-free at mean follow-up of 68 mos. Distant recurrence (DR) occurred in 7 patients at mean of 38 mo. Two local failures were associated with DR. Six patients died of disease after recurrence despite salvage systemic therapy. One patient developed isolated local failure (vaginal apex) and remains disease-free 37 mo after surgical/chemotherapeutic salvage. 5 of 8 (45%) stage IIIC patients developed recurrence vs. only 2 of 19 (10%) stage IIIA cases. 2 of 3 patients treated with extended field RT for positive para-aortic nodal disease remain disease-free at 128 and 56 mo. Long-term survival can be achieved in stage III endometrial carcinoma. Few patients with either adnexal metastases or positive cytology alone develop recurrence. However, patients with stage IIIC disease fare poorly with local therapy alone.

Silicone breast implants: an oncologic perspective.

In 1992, the FDA decided that silicone gel-filled breast implants would be available only through controlled clinical studies, despite the fact that they had been used for mammoplasty in millions of women around the world for more than 30 years. The safety of silicone breast implants had been called into question after several reports of a possible association between the implants and the subsequent development of connective tissue diseases. Such reports led to general public concern fueled by popular media attention and multiple class-action lawsuits against the product's manufacturers. It was in this climate that the FDA was forced to make its decision. This article reviews current scientific evidence on the safety of silicone gel-filled breast implants. Issues pertinent to oncology are highlighted. These include the possible carcinogenic effect of silicone gel, the safety of irradiating breasts with silicone implants, and the ability to mammographically image the implanted breast.

The impact of adjuvant radiotherapy on carcinosarcoma of the uterus.

BACKGROUND: The role of adjuvant radiotherapy in the setting of uterine carcinosarcoma has not been clearly established. METHODS: A retrospective review of 60 patients receiving definitive therapy for carcinosarcoma of the uterus was undertaken at a single institution. Twenty-nine of 60 patients were treated with adjuvant radiotherapy. RESULTS: The addition of radiotherapy significantly reduced the local recurrence rate from 55% (17 patients) to 3% (1 patient). Adjuvant radiotherapy reduced the risk of distant failure and death in patients with disease confined to the uterus but did not impact distant recurrence or survival in stage III patients. Increasing stage and depth of myometrial tumor invasion were negatively associated with overall survival and disease-free survival but had no impact on local recurrence rates. The nuclear grade of the epithelial component was predictive of local recurrence (P = 0.0592), but epithelial architectural grade, grade of stromal component, and stromal versus epithelial predominance did not provide prognostic information. The relative risk of local recurrence of unirradiated patients versus irradiated patients was 17.54 (P = 0.0055) after adjusting for nuclear grade of the epithelial component. CONCLUSIONS: Local failure represents a significant site of failure in the absence of adjuvant radiotherapy. The improvement in local failure rates with the addition of radiotherapy translates into an improvement in distant failure rates and survival only for patients with stage I/II disease. Epithelial nuclear grade, in addition to depth of myometrial invasion and stage, provides important prognostic information. Epithelial architectural grade, stromal grade, type of stromal component (homologous versus heterologous), and predominance of either stromal or epithelial component were not found to be significant prognostic factors.

Adjuvant radiation for vulvar carcinoma: improved local control.

PURPOSE: Local recurrence is a significant problem following primary surgery for advanced vulva carcinoma. The objectives of this study were to evaluate the impact of adjuvant vulvar radiation on local control in high risk patients and the impact of local recurrence on overall survival. METHODS AND MATERIALS: From 1980-1994, 62 patients with invasive vulva carcinoma and either positive or close (less 8 mm) margins of excision were retrospectively studied. Thirty-one patients were treated with adjuvant radiation therapy to the vulva and 31 patients were observed after surgery. Kaplan-Meier estimates and the Cox proportional hazard regression model were used to evaluate the effect of adjuvant radiation therapy on local recurrence and overall survival. Independent prognostic factors for local recurrence and survival were also assessed. RESULTS: Local recurrence occurred in 58% of observed patients and 16% in patients treated with adjuvant radiation therapy. Adjuvant radiation therapy significantly reduced local recurrence rates in both the close margin and positive margin groups (p = 0.036, p = 0.0048). On both univariate and multivariate analysis adjuvant radiation and margins of excision were significant prognostic predictors for local control. Significant determinants of actuarial survival included International Federation of Gynecologists and Obstetricians (FIGO) stage, percentage of pathologically positive inguinal nodes and margins of excision. The positive margin observed group had a significantly poorer actuarial 5 year survival than the other groups (p = 0.0016) and adjuvant radiation significantly improved survival for this group. The 2 year actuarial survival after developing local recurrence was 25%. Local recurrence was a significant predictor for death from vulva carcinoma (risk ratio 3.54). CONCLUSION: Local recurrence is a common occurrence in high risk patients. In this study adjuvant radiation therapy significantly reduced local recurrence rates and may improve overall survival in certain subgroups. As salvage rates after developing local recurrence are poor adjuvant vulvar radiation should be considered for patients at risk after primary surgery.