Advanced cervical cancer.

Several large, prospectively randomized clinical trials run by multi-institutional cooperative groups have established that the best treatment for advanced cancer of the cervix is primary radiotherapy with concurrent, cisplatin-based chemotherapy. In fact, patients with earlier stage cervix cancer with poor prognostic indicators (large, bulky tumors, positive pelvic lymph nodes, or unexpected parametrial disease at the time of surgery) also show a survival benefit with this approach. Adequate radiation dosing (both external beam and intracavitary) is essential. The additional benefit of periaortic lymph node irradiation is debated, but generally accepted, for patients with locally advanced disease or pelvic lymph node involvement.

Irradiation with or without misonidazole for patients with stages IIIB and IVA carcinoma of the cervix: final results of RTOG 80-05. Radiation Therapy Oncology Group.

PURPOSE: The purpose of this study was to evaluate tumor response, progression-free survival, local tumor control, patterns of relapse, and toxicity in patients with Stages IIIb and IVa squamous cell carcinoma of the uterine cervix treated with irradiation or irradiation and misonidazole. This is a report of the final results of the study. METHODS: This study was a prospective randomized Phase III trial performed by the Radiation Therapy Oncology Group (RTOG). Between August 1980 and November 1984, 120 patients with Stages IIIb and IVa squamous cell carcinoma of the cervix were randomized to receive either standard irradiation or standard irradiation and misonidazole. Irradiation consisted of 46 Gy to the pelvis plus a 10 Gy parametrial boost followed by intracavitary brachytherapy or external irradiation boost to the primary tumor. Misonidazole was administered at 400 mg/m2 daily, 2-4 h before irradiation. Patients in the 2 treatment groups were evenly distributed by stage, Karnofsky Performance Status, and positive para-aortic lymph nodes. RESULTS: Sixty-one patients were treated with irradiation alone, and 59 patients received irradiation and misonidazole. Complete response in the pelvis occurred in 44 (75%) of those treated with irradiation and in 38 (64%) of those treated with irradiation and misonidazole. The progression-free survivals were 22% at 5 years for the control group, and 29% at 5 years for the misonidazole group. At the time of last follow-up, 18 patients in the control arm were free of disease, and in the experimental arm, 19 were free of disease. The patterns of failure for those treated with irradiation alone were local-only in 9 patients, distant-only in 8 patients, and local and distant in 11 patients. The patterns of failure for those receiving irradiation and misonidazole were local-only in 3 patients, distant-only in 8 patients, and local and distant in 8 patients. The maximum toxicity experienced per patient was grade 3 in 18%, grade 4 in 8%, and no grade 5 toxicity for those treated with irradiation alone compared to 8%, 2%, and 2%, respectively, for the experimental arm. CONCLUSION: There were no statistically significant differences in pelvic response, disease-free survivals, patterns of failure, or toxicity for the irradiation alone group or for the irradiation and misonidazole group as administered in this study for patients with Stages IIIb and IVa squamous cell carcinoma of the uterine cervix.

Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma.

BACKGROUND: Bulky stage IB cervical cancers have a poorer prognosis than smaller stage I cervical cancers. For the Gynecologic Oncology Group, we conducted a trial to determine whether weekly infusions of cisplatin during radiotherapy improve progression-free and overall survival among patients with bulky stage IB cervical cancer. METHODS: Women with bulky stage IB cervical cancers (tumor, > or =4 cm in diameter) were randomly assigned to receive radiotherapy alone or in combination with cisplatin (40 mg per square meter of body-surface area once a week for up to six doses; maximal weekly dose, 70 mg), followed in all patients by adjuvant hysterectomy. Women with evidence of lymphadenopathy on computed tomographic scanning or lymphangiography were ineligible unless histologic analysis showed that there was no lymph-node involvement. The cumulative dose of external pelvic and intracavitary radiation was 75 Gy to point A (cervical parametrium) and 55 Gy to point B (pelvic wall). Cisplatin was given during external radiotherapy, and adjuvant hysterectomy was performed three to six weeks later. RESULTS: The relative risks of progression of disease and death among the 183 women assigned to receive radiotherapy and chemotherapy with cisplatin, as compared with the 186 women assigned to receive radiotherapy alone, were 0.51 (95 percent confidence interval, 0.34 to 0.75) and 0.54 (95 percent confidence interval, 0.34 to 0.86), respectively. The rates of both progression-free survival (P<0.001) and overall survival (P=0.008) were significantly higher in the combined-therapy group at four years. In the combined-therapy group there were higher frequencies of transient grade 3 (moderate) and grade 4 (severe) adverse hematologic effects (21 percent, vs. 2 percent in the radiotherapy group) and adverse gastrointestinal effects (14 percent vs. 5 percent). CONCLUSIONS: Adding weekly infusions of cisplatin to pelvic radiotherapy followed by hysterectomy significantly reduced the risk of disease recurrence and death in women with bulky stage IB cervical cancers.

Cell proliferation rate by MIB-1 immunohistochemistry predicts postradiation recurrence in prostatic adenocarcinomas.

We examined whether the cell proliferation index by MIB-1, HER-2/neu gene amplification, Gleason grade, and pretreatment level of serum prostate specific antigen (PSA) correlated with postradiation recurrence (PRR) in patients with prostatic adenocarcinoma. Formalin-fixed, paraffin-embedded tissue sections from 42 pretreated cases of prostatic adenocarcinoma (38 needle biopsy and 4 transurethral resection specimens) were immunostained for MIB-1 (MMI, Ventana Medical Systems, Tucson, Ariz). HER-2/neu gene amplification was analyzed by fluorescence in situ hybridization using the Oncor unique sequence probe (Oncor, Gaithersburg, Md). The cell proliferation index by MIB-1 was determined by labeling index; levels of HER-2/neu were analyzed semiquantitatively. Twenty-three of 42 patients (55%) were considered to have PRR on the basis of consecutive elevations of serum levels of PSA to greater than 1.5 ng/mL after completion of treatment (mean follow-up time, 33.4 months). The cell proliferation index correlated with PRR on both univariate and multivariate analyses. Of the 23 tumors that showed PRR, 18 (78%) revealed a high cell proliferation index, compared with 6 of 19 cases (32%) that showed no PRR. Twelve of 23 cases of prostatic adenocarcinoma (52%) in the recurrent group showed HER-2/neu gene amplification, compared with 5 of 19 (26%) in the nonrecurrent group; these findings reached near significance on univariate analysis. Pretreatment levels of serum PSA also reached significance on multivariate analysis. In this preliminary study, the cell proliferation index by MIB-1 reached independent significance in predicting PRR in patients with prostatic adenocarcinoma, whereas HER-2/neu amplification by fluorescence in situ hybridization reached near significance.

Extended field radiation and cisplatin for stage IIB and IIIB cervical carcinoma.

OBJECTIVE: The aim of this study was to investigate local regional control, survival, and morbidity in patients with FIGO IIB and IIIB squamous cell carcinoma of the cervix treated with primary extended field (prophylactic paraaoratic radiation) radiation and weekly cisplatin. METHODS: Sixty-seven patients (44 IIB and 23 IIIB) with carcinoma of the cervix received cisplatin at 1 mg/kg (up to 60 mg) weekly and extended field radiation therapy including the paraaortic nodes and brachytherapy. RESULTS: After the scheduled therapy 94.1% of the patients were complete responders. Seventy-five percent are alive without evidence of disease with a mean follow-up of 47.5 months. CONCLUSION: This study confirms the ability to give concomitant weekly cisplatin and prophylactic paraaortic radiation with minimal morbidity. The encouraging Kaplan-Meier survival of 75% and only eight pelvic failures warrants further investigation.

Primary radiation, cisplatin, and 5-fluorouracil for advanced squamous carcinoma of the vulva.

OBJECTIVE: To evaluate a regimen of radiation and chemotherapy as an alternative for those patients in whom the location and extent of advanced vulvar carcinoma make pelvic exenteration the only surgical option. METHODS: Between December 1988 and March 1995, 14 patients with primary squamous carcinoma of the vulva who were not candidates for standard radical vulvectomy were treated with radiation therapy in combination with cisplatin and 5-fluorouracil (5-FU) chemotherapy at the Albany Medical Center. Patients ranged in age from 40 to 90 years, mean 68. Tumors were stage III in 9 patients and stage IV in 5 patients. Treatment included two cycles of chemotherapy with cisplatin (50 mg/m2) and 5-FU (1000 mg/m2/24 x 96 hr) in addition to radiation therapy. Total radiation doses to the vulva and groins ranged from 50 to 65 Gray (Gy), with pelvic doses of 45 to 50 Gy. Surgical excision of the primary site was not performed in patients who had complete clinical response. RESULTS: Acute complications included desquamation requiring treatment interruptions in 5 patients and deep venous thrombosis in 1 patient. Delayed complications were limited to small bowel obstruction and colonic stricture in one patient. There was a 92% response rate with complete responses in 9 patients (64%). Among patients with complete clinical response, there has been only one recurrence with follow-up of 7-81 months, mean 36.5. All patients with partial responses died, with survival of 8-25 months, mean 15.7. CONCLUSIONS: This combination of chemoradiation was found to be effective therapy for locally advanced vulvar carcinoma, with acceptable morbidity even in an elderly population. Surgical excision of the primary site is not necessary in patients with complete response.

Optimal management of locally advanced cervical carcinoma.

Locally advanced or recurrent cervical cancer is highly responsive to treatment and at least moderately curable with effective aggressive treatment. Radiation therapy is the mainstay of treatment for patients with this cancer. The roles for surgery and chemotherapy are as yet unproved, and both modalities are currently under investigation for their potential roles in the management of these conditions. Exenterative surgery clearly has an established utility for central pelvic failures after prior radiation therapy. Postsurgical pelvic recurrences are rarely successfully treated for cure, but considerable palliative effect is possible. The roles of intraoperative irradiation, sensitizing chemotherapy, and radical resection with interstitial irradiation are all under investigation at this time. Much has been learned over the past several decades about what parameters are important for successful radiation therapy for cervical cancers of stages IIB-IVA. While the traditional staging work-up for these patients included excretory urography, barium enema, examination under anesthesia, cystoscopy, and proctoscopy, there is now good evidence that computed tomography scan with intravenous contrast and office examination and biopsy are sufficient, with cystoscopy reserved for those few patients in whom clinical or imaging data suggest a higher risk of involvement. Surgical lymph node staging, especially of para-aortic lymph nodes, may be worthwhile in certain settings (e.g., for entry into research protocols), but it has no demonstrated role in routine clinical practice. Evidence is clear and convincing that effective treatment for these disease stages requires the inclusion of intracavitary brachytherapy. The role of interstitial brachytherapy is less clear, although there are some fervent advocates of this procedure. The debate continues about the use of low-dose-rate versus high-dose-rate brachytherapy. Treatment dose, volume, and length of treatment course are all important variables with outcome implications. The central disease requires a total dose of 8000-9000 cGy for maximal control probability, with larger tumors requiring the higher doses. The three-dimensional treatment volume must adequately surround the cancer and its likely routes of spread. Overall treatment time should be kept as short as possible, within the limits of conventional, tolerable fractionation. The potential theoretical advantage of hyperfractionated external-beam irradiation has yet to be verified in this disease but is of interest. It will be tested in an upcoming Gynecologic Oncology Group clinical trial. The negative prognostic significance of hypoxia in cervical cancers in general has been reported recently. While tumor cell hypoxia is almost certainly a problem in this disease, hypoxic cell sensitizers have not yet been found to improve treatment results. In clinical practice, reoxygenation probably occurs in these tumors. The role of paraaortic lymph node elective irradiation has been of interest for more than 20 years and was the subject of two randomized trials with quite different results. The Radiation Therapy Oncology Group trial found significantly improved survival in the treatment group assigned to receive paraaortic irradiation, when compared with the pelvic treatment group. However, a similar study by the European Organization for Research and Treatment of Cancer found no difference. The results of treatment today are substantially improved from those seen two decades ago. About 75% of patients with stage IIB disease and fully 50% of patients with stage IIIB disease are now cured with conventional irradiation alone. Clearly, there is still a need for further improvement. Of patients with urinary bladder involvement, 10%-20% are long-term survivors, as are 25%-30% of patients with para-aortic lymph node metastases. While these improvements are significant, there is clearly room for further progress. (ABSTRACT TRUNCATED)

Hydroxyurea versus misonidazole with radiation in cervical carcinoma: long-term follow-up of a Gynecologic Oncology Group trial.

PURPOSE: Long-term follow-up data of a randomized trial that compared hydroxyurea and the hypoxic-cell radiosensitizer to misonidazole as adjuncts to standard radiation therapy in locally advanced carcinoma of the cervix are reported. PATIENTS AND METHODS: Three hundred eight women were entered, and all 294 eligible patients are assessable as randomized. Eighty-one percent of patients have been monitored for 5 years or to death. RESULTS: There was an advantage for hydroxyurea in progression-free interval and survival (P = .05 and P = .066, respectively). There was no significant difference in the distribution of sites of failure between the regimens. For the 39% of patients with stages III to IVA disease, the advantage in progression-free interval for hydroxyurea was significant (47.8% v 33.6%). More leukopenia occurred on the hydroxyurea regimen than on the misonidazole regimen. CONCLUSION: In summary, these data provide stronger evidence than our previous analysis that hydroxyurea is superior to misonidazole as an adjunct to radiation therapy. For patients with locally advanced carcinoma of the cervix, hydroxyurea continues to be the adjunct of choice with radiation.

Weekly cisplatin and radical radiation therapy for advanced, recurrent, and poor prognosis cervical carcinoma.

BACKGROUND: A Phase I-II trial of cisplatin and radical radiation therapy was initiated for advanced, recurrent, and poor prognosis carcinoma of the uterine cervix. METHODS: From September 1983 to October 1991, 55 patients were entered on the protocol. Forty patients had advanced cervical carcinoma International Federation of Gynecology and Obstetrics (FIGO) Stages IIB-IVB, 4 patients were treated for recurrent disease, and 11 patients had FIGO Stage I disease with poor prognostic factors. Cisplatin was administered weekly on an outpatient basis at a dose of 1 mg/kg (maximum, 60 mg) during teletherapy. The radiation fields included the pelvis only in 20 patients, the pelvis and paraaortic fields in 33 patients, and the paraaortic fields alone in 2 patients. The total number of cycles of cisplatin received ranged from 3-6 (mean 5.2). There were no interruptions in the planned radiation therapy. RESULTS: Neutropenia occurred in 18 of 55 patients (32.7%) with only 1 (1.8%) having Grade IV toxicity. Mild thrombocytopenia occurred in only one patient. No significant gastrointestinal, neurologic, or renal toxicity was observed. Of the 48 patients with measurable or evaluable disease, all had a complete response within the radiation field. The follow-up has ranged from 1-85+ months. Currently, there have been 19 (34.5%) recurrences, only 2 (3.7%) of which have occurred in the radiation field. CONCLUSIONS: The weekly cisplatin chemotherapy administered during radiation therapy was well tolerated in this high-risk group of patients and did not diminish the ability to give standard doses of radiation.

Gynecologic Oncology Group randomized trials of combined technique therapy for vulvar cancer.

The Gynecologic Oncology Group (GOG) did a surgicopathologic study of vulvar cancer in which various prognostic factors in the primary lesion were evaluated and compared with the pathologic status of the lymph nodes in the groin dissections. In total, 558 patients were entered into this study (GOG Protocol 36) from November 1977 to February 1984. The 203 patients with positive groin nodes were eligible for a second study in which they were assigned randomly to receive either pelvic lymph node dissection or pelvic and groin irradiation (Protocol 37). One hundred fourteen patients were randomized to this study, and 53 of 59 patients in each treatment arm actually underwent the prescribed treatment. Acute and late toxicities were similar in both treatment arms. There was a significant difference in survival rate that favored the pelvic radiation treatment (P = 0.03). The largest difference in survival rates occurred in those patients with either of the poor prognostic findings (clinically suspicious fixed ulcerated nodes or two or more positive nodes). The 2-year survival rate was 68% for the radiation treatment arm and 54% for the surgical program. Pelvic radiation therapy has become the standard treatment for patients with positive groin nodes, especially if they are fixed or multiple. Based on these results, a subsequent study was designed to test whether radiation therapy could substitute for bilateral groin node dissection in patients with vulvar cancer (Protocol 88). Fifty-eight patients were enrolled in the study before entry was suspended on April 30, 1991, and the study was closed on November 1, 1991. In the first 49 evaluable patients, there were five groin recurrences in the irradiated patients, although there were no groin failures in the operated group. The radiation program used in this study may not have provided an adequate dose to the depth where the lymph nodes were located because the prescription called for dose calculations at a depth of 3 cm. Unless demonstrated in another study, groin irradiation cannot be used as an equivalent option to groin dissection. Aggressive preoperative chemoradiation treatment currently is being studied for patients with T3 lesions not amenable to standard radical vulvectomy. Surgical dissection of residual tumor plus bilateral groin dissections are to be done if the postradiation biopsy findings are positive. Patients with unresectable Stage T2 or T3 groin nodes are also eligible for this study (Protocol 101).

Aggressive multimodality treatment for cervical cancer with paraaortic lymph node metastases.

A Phase I/II trial of weekly cisplatin and extended field radiation therapy for cervical carcinoma and paraaortic metastases was initiated. A total of 13 patients have entered this trial since 1985. The objective of the study was to determine the efficacy and toxicity of extended field radiation therapy and cisplatin as a radiation sensitizer in this high-risk group of patients. The addition of paraaortic nodal radiation was derived from our earlier trial using cisplatin and pelvic radiation therapy followed by combination chemotherapy (cisplatin, adriamycin and cytoxan). Of the 13 patients entered, 8 are alive without evidence of disease and 5 have recurred, all exclusively outside the treatment fields. Three of the five had positive scalene node biopsies prior to the initiation of therapy. Four patients have died from distant metastases, one is alive with lung and bone metastases, and there have been no recurrences in the pelvis or paraaortic treated areas. The encouraging results of complete local and pelvic control of tumor and acceptable toxicity warrants continuation of this trial.

Carcinoma of the cervix treated with radiation therapy. I. A multi-variate analysis of prognostic variables in the Gynecologic Oncology Group.

Between 1977 and 1985, the Gynecologic Oncology Group (GOG) conducted three clinical trials in locally advanced carcinoma of the cervix, clinical Stages I to IVA as classified by the International Federation of Gynecology and Obstetrics (FIGO). All 626 patients had primary carcinoma of the cervix and underwent operative assessment of the para-aortic (PA) lymph nodes. Patients received standardized external radiation therapy to the pelvis or to the pelvis and PA lymph nodes followed by one or two brachytherapy applications. To date, no statistically significant differences in progression-free interval (PFI) or survival time have been identified between the randomization treatment arms on any of these studies. Basic similarities among these studies led us to pool these data to identify patient characteristics and tumor characteristics associated with an increased risk of treatment failure. Multi-variate analysis showed patient age, performance status (PS), PA lymph node status, tumor size, and pelvic node status to be significantly associated with PFI. When modeling for survival, all these factors and clinical stage and bilateral extension were significant.

Simultaneous presentation of adenocarcinoma of prostate and transitional cell carcinoma of bladder.

Simultaneous presentation of transitional cell carcinoma of the bladder and adenocarcinoma of the prostate is not uncommon. Twenty-two patients were diagnosed as having simultaneous or concurrent presentation of prostate and bladder carcinomas between January 1970 and July 1986. The overall five-year survival was 40 percent, with patients presenting with prostate cancer doing better (50%) than those with bladder cancer (32%). Retrospective review of these cases suggests that primary therapy should be directed to the most advanced cancer. Incidental prostate cancer may be "cured" with a cystoprostatectomy and, when indicated, radiation therapy added postoperatively for the bladder cancer. Eleven patients presented with Stage A prostate cancer: 10 of the 11 were treated for their bladder cancer. Treatment was usually radical cystoprostatectomy with or without postoperative radiation. None died of prostate cancer. Patients presenting with advanced stage prostate cancer have had recurrence or have died of the cancer.

A randomized trial of hydroxyurea versus misonidazole adjunct to radiation therapy in carcinoma of the cervix. A preliminary report of a Gynecologic Oncology Group study.

Between June 1981 and December 1985, 296 evaluable patients with carcinoma of the cervix (stages IIB, III, or IVA) were randomized to radiation therapy and either hydroxyurea (139 patients) or misonidazole (157 patients). All patients had undergone clinical, radiographic, and surgical staging. Patients with metastasis to periaortic nodes were ineligible for study. Patients received external radiation therapy to the pelvis and either one or two intracavitary applications. Hydroxyurea was given in a dose of 80 mg/kg each Monday and Thursday during external radiation therapy. Misonidazole was given in a dose of 1 gm/m2 in the same schedule, not to exceed 12 gm/m2. Of the evaluable patients, 60.8% had stage IIB disease and 33.8% had stage IIIB disease. Negative pelvic lymph nodes were found in 79.2% of the patients. Median age was 49 years (first and third quartiles 40 and 60, respectively). There were 51 patients who had severe and 15 patients who had life-threatening adverse effects (including two treatment-related deaths). As of February 1987 half the patients have either failed or been followed-up for at least 43 months. The group treated with hydroxyurea had a longer progression-free interval, bordering on statistical significance, than those treated with misonidazole (p = 0.08). The median progression-free interval for all patients randomized to hydroxyurea is 42.9 months and for misonidazole it is 40.4 months. The median progression-free interval for patients with stage III and IV disease who received hydroxyurea has not been reached and for the misonidazole group it was 10.1 months. There have been 120 recurrences, 51 (36.7%) in the hydroxyurea group and 69 (43.9%) in the misonidazole group; 51.7% of the recurrences have been limited to the pelvis or vagina. Failure limited to the pelvis occurred in 18.0% of patients receiving hydroxyurea and 23.6% of patients receiving misonidazole. There were 108 deaths, 47 (33.8%) in the hydroxyurea group and 61 (38.9%) in the misonidazole group; survival does not differ statistically between the two regimens at this point in follow-up (p = 0.25). Hydroxyurea has more short-term gastrointestinal and marrow toxicity, but is free of long-term neurotoxicity. Preliminary analyses indicate that there is no role for radiation therapy with misonidazole in cervical carcinoma.

Reducing the negative impact of radiation therapy on functional status.

The effect of an informational intervention that provided objective descriptions, in concrete terms, of the usual experiences during the various phases of radiation therapy was tested in a random clinical trial. The patients had Stage A, B, or C prostatic cancer. Forty-two control patients received the information routinely provided to all patients in the treatment setting. Forty-two experimental patients received, in addition, four informational messages during the course of radiation therapy. The first message described the experience of treatment planning; the second described the experience of receiving a radiation treatment; the third described side effects that usually occur, their onset, their characteristics, and activities to lessen their impact; and the fourth described the usual experiences during the months following radiation treatments. The experimental group of patients, compared with those in the control group, reported significantly less disruption in usual activities during and following radiation therapy. The amount of emotional disturbance was low and did not differ by study group. The results of this study, with respect to the interventions' effect on radiation therapy patients' quality of life, were consistent with prior research in other health care situations.

Absence of prognostic significance, peritoneal dissemination and treatment advantage in endometrial cancer patients with positive peritoneal cytology.

Peritoneal cytology has been shown to be one of the prognostic factors in endometrial cancer. A series of 134 patients was seen between January 1977 and March 1985 with clinical Stage I (or treated as a clinical Stage I) endometrial adenocarcinoma at the University of Rochester Cancer Center. The majority of patients underwent extrafascial hysterectomy with the majority of washings obtained at the time of surgery. Fourteen percent (19/134) of the patients were found to have positive cytology. Eleven patients with positive cytology (11/19) were treated with local-regional pelvic treatment; the other eight patients received whole abdominal therapy. The recurrence rates were less with the local treatment than with the whole abdominal treatment groups (9.1% vs. 25%) in those patients having positive cytology. There was no statistical difference in recurrence rates between the pathologic Stage I patients with positive cytology (10%) versus those patients having negative cytology (5%), nor was there statistical difference in survival between pathologic Stage I positive or negative cytology patients. It is suggestive from this non-randomized study that positive cytology in endometrial cancer is not an independent prognostic factor and that whole abdominal irradiation did not influence outcome.

Prevention of heterotopic bone formation with early post operative irradiation in high risk patients undergoing total hip arthroplasty: comparison of 10.00 Gy vs 20.00 Gy schedules.

Prior studies have demonstrated the effectiveness of postoperative radiation therapy (RT) to the hip area following total hip replacement (THR) surgery in preventing the development of heterotopic bone formation in patients considered to be at high risk for development of this complication. Previously, patients received 20.00 Gy in 10 fractions (fx) over 2 weeks, beginning as soon postop as medically feasible (usually post-op day 2). In an effort to reduce hospital stay and risk of secondary malignancy, a prospective treatment program was initiated April 1982 using a reduced dose of 10.00 Gy in 5 fx over 5-7 days. As of February 1984, 46 consecutive hips determined to be at high risk were treated with this reduced dose. Prior studies have demonstrated that heterotopic bone is always radiographically evident by 8 weeks. Of the 46 hips, 41 had been evaluated with the minimum required 8 week follow-up X ray. Twenty-five of these hips, 61%, had a mean long term follow-up of 12 months. Our historical control group, consisting of 54 consecutive high risk post-THR's, was shown to have a 68.5% incidence of heterotopic bone. The 20.00 Gy group, when RT was started by post-op day 5, demonstrated a 3.2% incidence, compared to 4.9% in the 10.00 Gy group. Complication rates were also comparable in the two RT groups, 19.4% and 7.3% respectively; 10.00 Gy is apparently as effective as 20.00 Gy in preventing heterotopic bone formation in high risk post-THR patients.

Systemic hemibody irradiation for overt and occult metastases.

Hemibody irradiation was initially employed as a palliative technique to treat diffuse metastatic disease in one session as opposed to multiple fields over an extended period. It provides a radiation treatment for disseminated cancer and therefore has been termed "systemic" therapy. Since it is possible to treat both halves of the body sequentially, it allows radiation treatment to the whole body in larger doses than could be accomplished with total-body irradiation. Because of the success in terms of dramatic rapid pain relief and the objective response on metastatic disease, it has been explored in the treatment of occult disease and as consolidation therapy in patients with tumors that have responded to chemotherapy. When hemibody irradiation is combined with chemotherapy, responses have been shown in metastases for several primaries, particularly small cell carcinoma, which is perhaps the most encouraging, and supports further research in the treatment of micrometastatic disease for this tumor type. As the technique moves from its current research phase into more general clinical use, radiation oncologists should become more familiar with the treatment, and the hospitalization originally required may be able to be avoided. An intensive premedication program has been developed to facilitate this. Innovative approaches using radiosensitizers, radioprotectors, hyperthermia, and hyperfractionation are ideas that are starting to be tested and will be further explored in the near future.

Survival and patterns of recurrence in cervical cancer metastatic to periaortic lymph nodes (a Gynecologic Oncology Group study).

Ninety-eight of 621 evaluable patients (16%) with cervical cancer enrolled into Gynecologic Oncology Group protocols were found to have periaortic lymph node metastases at staging laparotomy or at exploration for definitive operative management. As expected there was a progressive increase in the prevalence of periaortic metastases including 5% of 150 patients with Stage IB, 16% of 222 patients with Stage II, and 25% of 135 patients with Stage III. Periaortic lymph node metastases in the absence of pelvic lymph node metastases was an infrequent occurrence in patients so evaluated. The median survival of patients with periaortic metastases was 15.2 months with a survival probability of 25% at 3 years. The median duration of survival following recurrence was only 5 months. Recurrences were divided approximately equally between the pelvis and distant sites.

Usefulness of postoperative hip irradiation in the prevention of heterotopic bone formation in a high risk group of patients.

Heterotopic ossification is a complication of total hip arthroplasty in 14 to 30% of patients. Significant functional impairment will occur in up to 28% of patients with ectopic bone. The high risk group includes those with preexisting heterotopic bone in either hip, those suffering from hypertrophic osteoarthritis or ankylosing spondylitis and patients who have had multiple procedures on the hip. Fifty-eight patients (67 hips) were irradiated after surgical removal of ectopic bone (53 hips) or received radiation prophylaxis of heterotopic ossification (14 hips). Ninety-five percent of patients had either no bone visible or insignificant amounts of ectopic bone visible on postoperative hip X-rays. Only 5% of patients showed significant persistence of ectopic bone. Postoperative hip function was dramatically improved compared to preoperative function in all patients treated. The importance of early commencement of irradiation is emphasized.