Results and prognostic factors in the retreatment of locally recurrent nasopharyngeal carcinoma

PURPOSE: To review the results and evaluate the prognostic factors in the retreatment of locally recurrent nasopharyngeal carcinoma. METHODS AND MATERIALS: We reviewed the records of 74 patients with locally recurrent nasopharyngeal carcinoma treated at the University of California, San Francisco between 1957 and 1995. The histologic types included squamous cell carcinoma in 6 (8.1%), nonkeratinizing carcinoma in 48 (64.9%), and undifferentiated carcinoma in 20 (27%) cases. The site of recurrence was in the primary in 46 (62.2%), in the neck nodes in 20 (27%), and in both sites in 8 (10.8%) patients. The recurrent disease was Stage I in 10 (13.5%), Stage II in 16 (21.6%), Stage III in 20 (27%), and Stage IV in 28 (37.9%) patients. Thirty-seven (50%) patients developed recurrence within 2 years and 58 (78.4%) within 5 years after initial treatment. Radiotherapeutic techniques used in the retreatment of primary recurrence consisted of external beam radiotherapy (EBRT), intracavitary brachytherapy, heavy-charged particle beam, and gamma knife, alone or in combination. Reirradiation doses ranged from 18 to 108 Gy, with a median dose of 60 Gy. Treatment of recurrent neck nodes consisted of radical neck dissection (RND) +/- intraoperative radiotherapy (IORT), or EBRT +/- hyperthermia, or chemotherapy +/- hyperthermia. Chemotherapy was used in 22 (30%) patients. Median follow-up was 20 months (range: 2 to 308 months). RESULTS: The 3-, 5-, and 10-year actuarial overall survival following retreatment were 49, 37, 18%, respectively. Thirty-six patients (49%) were free of further local-regional recurrence after retreatment. The 3-, 5-, and 10-year local-regional progression-free rates were 52, 40, and 38%, respectively. On univariate analysis, histologic type (p < 0.0001), interval to recurrence (p = 0.034), and treatment modality for early-stage disease (p = 0.01) were significant prognostic factors for overall survival, with age being marginally significant (p = 0.053). For local-regional progression-free rate, only histology was significant (p = 0.035). On multivariate analysis, age (p = 0.026), histology (p = 0.015), and interval to recurrence (p = 0.030) were significant for overall survival, and only histology (p = 0.002) and presence of complications (p = 0.016) were significant for local-regional progression-free rate. Of the 64 reirradiated patients, late complications were documented in 29 (45%) patients. The late complications were permanent in 21 (33%) and severe in 15 (23%) patients. CONCLUSION: Retreatment using radiotherapy alone or in combination with other treatment modalities can achieve long-term local-regional control and survival in a substantial proportion of patients with locally recurrent nasopharyngeal carcinoma. Age, histology, and interval to recurrence were independent prognostic factors for overall survival, but only histology and presence of complications were significant for local-regional progression-free rate.     

Locally advanced primary colorectal cancer: intraoperative electron and external beam irradiation +/- 5-FU

PURPOSE: For locally advanced primary colorectal cancer, our institution has combined intraoperative electron irradiation (IOERT) with external beam irradiation (EBRT) +/- 5-fluorouracil (5-FU) and surgical resection. Disease control and survival were compared with the current IOERT and prior non-IOERT regimens. METHODS AND MATERIALS: From April 1981 through August 1995, 61 patients received an IOERT dose of 10-20 Gy, usually combined with 45-55 Gy of fractionated EBRT; 56 had minimum follow-up of 18 months. The amount of residual disease remaining at IOERT after exploration and maximal resection in the 56 patients was gross in 16, < or = microscopic in 39, and unresected in 1. RESULTS: Survival (SR) and disease control were analyzed as a function of potential prognostic factors. Factors that achieved statistical significance for improved overall survival included treatment sequence of preop EBRT + 5-FU (vs. postoperative EBRT + 5-FU, p = 0.003) and < or = microscopic residual disease after maximal resection (vs. gross residual, p = 0.005). Those that appeared to favorably impact disease-free survival included EBRT + 5-FU (vs. EBRT alone, p = 0.01), < or = microscopic residual (vs. gross, p = 0.0014), and colon site of primary (vs. rectum, p = 0.009). Failures within an irradiation field have occurred in 4 of 16 patients (25%) who presented with gross residual after partial resection vs. 2 of 39 (5%) with < or = microscopic residual after gross total resection (p = 0.01). The significant prognostic factors for a decrease in distant metastases were the same as for disease-free SR with respective p-values of 0.013 (EBRT + 5-FU), 0.008 (microscopic residual), and 0.03 (colon primary). The current data suggests a relationship between IOERT dose and incidence of Grade 2 or 3 neuropathy (< or = 12.5 Gy--1 of 29 or 3%, > or = 15 Gy--6 of 26 or 23%, p = 0.03). CONCLUSIONS: Both overall survival and disease control appear to be improved with the addition of IOERT to standard treatment. More routine use of systemic therapy is indicated as a component of IOERT containing treatment regimens because the incidence of distant metastases was 50% of patients at risk.     

Effect of adjuvant iridium-192 brachytherapy on the survival of patients with malignant gliomas

The effect of iridium-192 brachytherapy (BRTX) on the survival of patients with malignant gliomas was evaluated in 83 patients with malignant gliomas (42 astrocytoma grade III, 41 glioblastoma multiforme) over a period of 8.5 years. Fifty patients (Group 1) received only standard external beam radiotherapy (EBRT) (mean dose 51.5 +/- 12.4 Gy in 2.0 Gy fractions), and 33 patients (Group 2) received EBRT (mean dose 51.0 +/- 10.8 Gy) combined with BRTX (mean dose 50.2 +/- 13.2 Gy, dose rate of 0.3-0.4 Gy/hr). The median survival periods for patients in Groups 1 and 2 were 12.2 and 23.7 months, respectively (p = 0.0145). The median survival for 17 patients in Group 2 with glioblastoma multiforme was 21.9 months. Using BRTX as an adjuvant to EBRT appeared to confer survival benefits compared to only EBRT (p = 0.0284). Univariate and multivariate analysis identified the variables of histological diagnosis, location, Karnofsky performance status, and BRTX as relevant risk factors for survival time (p < 0.05 for each factor). Among these factors, BRTX was the most important for prolonging survival (p = 0.0015). Adjuvant iridium-192 BRTX and conventional EBRT appears to greatly improve the survival time of patients with malignant gliomas compared to only EBRT and may be the treatment of choice in selected patients with tumors located in deep-seated or eloquent areas.     

Intraoperative brachytherapy, laryngopharyngoesophagectomy, and gastric transposition for patients with recurrent hypopharyngeal and cervical esophageal carcinoma

OBJECTIVE: To evaluate the role of laryngopharyngoesophagectomy (LPE), intraoperative 125I brachytherapy (IOBT), and gastric transposition (GT) in patients with recurrent carcinoma involving the hypopharynx, or cervical esophagus. METHODS: Between 1988 and 1994 a total of 21 patients were managed with LPE/IOBT/GT. All patients had documentation of recurrent disease at the hypopharynx or cervical esophagus and had previously been treated with external-beam radiation (EBRT) to a total median dose of 60 Gy. Median age was 67 years, with 17 male patients and four female. IOBT was performed in all cases with permanent 125I implantation. Medical records were retrospectively reviewed. Overall survival, local control, and complications were evaluated. Median follow-up was 6 months. RESULTS: The median activity of 125I was 36 mCi, with a median dose of 80 Gy to the region at risk. Fifteen patients had lymph node dissections performed in conjunction with LPE, and 10 patients had nodal involvement on pathologic examination. Margins were microscopically positive in nine patients, and lymphvascular space invasion noted in 13. Actuarial survival at 1 and 3 years was 32% and 14%, respectively, with patients alive and with local control at 6, 24, 36, and 48 months (negative margins). Actuarial local control at 1 and 3 years was 63%. Complications included fistula in five patients, facial edema in four, protracted facial pain in two, cervical abscess in one, and mucosal hemorrhage in one. CONCLUSION: Patients with recurrent carcinoma of the hypopharynx or cervical esophagus after EBRT have an extremely poor prognosis. LPE, IOBT, and GT may provide very good local control for all candidates and prolonged survival for a small percentage of patients with an acceptable risk profile.     

The effect of combined external beam radiotherapy and brachytherapy on local control and wound complications in patients with high-grade soft tissue sarcomas of the extremity with positive microscopic margin

PURPOSE: A previously reported randomized trial from out institution demonstrated a local control advantage to adjuvant brachytherapy (BRT) for completely resected high grade soft tissue sarcoma (STS). In recent years, BRT boost has been combined with wide field external beam radiotherapy (EBRT) for selected patients in whom the margin(s) of resection was positive. This study evaluates the impact of BRT boost plus EBRT on local control in this subset of patients and on wound complication rates. METHODS AND MATERIALS: Between January, 1987 and December, 1992, 105 adult patients with primary or locally recurrent high grade STS of the extremity were treated with wide local excision and BRT alone (87 patients; dose: 45 Gy) or BRT plus EBRT (18 patients; dose: 15-20 Gy BRT + 45-50 Gy EBRT). The margin(s) of resection was positive in 10 out of 18 patients in the BRT + EBRT group vs. 17 out of 87 patients in the BRT alone group. Wound complications were classified as major if they required further operative intervention; moderate if there was purulent discharge, hematoma > 25 ml, wound separation > 2 cm, and persistent seroma requiring drainage; or minor if less than moderate. Median follow-up was 22 months. RESULTS: The overall 2-year actuarial local control rate was 86%. There was no difference in the 2-year actuarial local control rate between the BRT + EBRT group (90%) and the BRT alone group (82%) (9 = 0.32). However, for patients with positive resection margins the use of BRT + EBRT produced better local control than BRT alone [9 out of 10 (90%) vs. 10 out of 17 (59%)]. This difference approached but did not reach statistical significance (p = 0.08). No difference was seen in patients with negative margins. There was no significant difference in the overall wound complication rate (26% BRT vs. 38% BRT + EBRT, p = 0.31) nor in the combined major and moderate wound complication rate (16% BRT vs. 27% BRT + EBRT, p = 0.39). CONCLUSION: Our preliminary data suggest a trend in favor of BRT boost + EBRT as the optimal adjuvant local strategy for STS with positive resection margins. There is no significant difference in the wound complication rate with either technique.     

Myelination of the brain in MRI: a staging system

CORT has been developed to treat recurrent gynaecological malignancies infiltrating the pelvic wall unilaterally. The surgical part consists of: (i) staging laparotomy/lymphadenectomy, (ii) maximum tumour resection at the pelvic wall and exenteration of infiltrated central pelvic organs, (iii) implantation of guiding tubes on the residual tumour/tumour bed on the pelvic wall, (iv) pelvic wall plasty with muscle, musculocutaneous and omentum flaps, (v) operative reconstruction of bowel, bladder and perineo-vulvo-vaginal functions. Radiation is performed as interstitial high dose rate brachytherapy through the implanted tubes. Patients without prior pelvic irradiation receive in addition, whole pelvis teletherapy. CORT has been evaluated in a prospective phase I and II trial at the University of Mainz. Within a 3-year period, 21 patients with pelvic wall recurrences from various gynaecological primary tumours were treated. Seventeen patients had been irradiated as (part of) the previous therapy with a median total mid-pelvic dose of 65 Gy (range 40-100 Gy). There was no operative mortality. Five patients developed complications necessitating surgical intervention. One patient died from fatal thromboembolism 6 months after CORT without evidence of tumour progression. In 14 patients, local tumour control has been achieved. After a median follow-up period of 27 months (range 6-38 months) Kaplan-Meier life table analysis revealed an actuarial survival probability of 55% (recurrence-free 49%). We conclude from these preliminary results, that the CORT procedure for the treatment of pelvic wall recurrences is feasible and may lead to encouraging therapeutic success in selected patients, whose situation had been hopeless so far.     

The activated clotting time loading dose response ratio (ACTLORR) as an indicator of heparin demand during cardiopulmonary bypass

PURPOSE: To develop a new technique, intraoperative high dose rate brachytherapy (IOHDR), to deliver localized radiation therapy intraoperatively to head and neck tumors at sites inaccessible to intraoperative electron beam radiotherapy (IOEBRT) in the skull base region. METHODS: After maximal surgical resection, afterloading catheters spaced 1 cm apart embedded in custom surface applicators made of foam or silicone were placed on resected tumor beds. IOHDR was delivered in a shielded operating room using preplanned dosimetry with a nominal 10 Ci iridium-192 source in an HDR micro-Selectron afterloader. Twenty-nine patients (20 males, 9 females) ranging in age from 9 to 80 years (median = 61) were irradiated intraoperatively for advanced head and neck tumors at sites inaccessible to IOEBRT. Six patients who had previously received external beam radiation (EBRT) ranging from 50 to 75 Gy, were given 15 Gy of IOHDR only. Twenty-three patients who had no prior radiation received 7.5 to 12.5 Gy IOHDR, and 45 to 50 Gy EBRT was planned post-operatively; however, six of these patients did not complete the planned EBRT. Doses to normal tissues were reduced whenever possible by shielding with lead or by displacement with gauze or retractors. Treatment time ranged from 3.8 to 23 min (median = 6.5 min). Five patients received concurrent cis-platinum based chemotherapy. RESULTS: Twenty-nine patients treated to 30 sites had local tumor control of 67% and crade survival of 72%, with the follow-up ranging from 3 to 33 months (median = 21 months). In the group of 17 previously unirradiated patients who had completed full treatment (IOHDR and EBRT) to 18 sites, the local tumor control was 89%, and all of these patients survived. Tumor control in the six previously unirradiated patients who did not complete EBRT was 50% with a crude survival of 50%. In the group of six previously irradiated patients treated by IOHDR only, the local tumor control was 17% with a crude survival of 17%. No intraoperative complications were noted. The delayed morbidity included cerebrospinal fluid (CSF) leak with bone exposure (1), chronic subdural hematoma (1), septicemia (1), otitis media (1), and severe xerostomia (1). We cannot comment on long-term morbidity due to the relatively short follow-up period of 21 months. CONCLUSIONS: It is feasible to deliver IOHDR, with acceptable toxicity, to skull base tumors at sites inaccessible to IOEBRT. The use of IOHDR as a pre-radiotherapy boost produced excellent local control and survival in the selected group of patients who had no previous radiation therapy. The use of exclusive IOHDR in the previously irradiated group resulted in poor outcome, possibly due to the limitations on re-irradiation doses and/or volumes determined by normal tissue tolerance or because these patients have inherently radioresistant tumors. Higher IOHDR doses, additional EBRT, and/or chemotherapy should be considered for this group. The use of IOHDR as a pre-EBRT boost to maximize local control has a promising future in the treatment of carefully selected patients with advanced skull base tumor.     

Treatment results and prognostic factors in 101 men treated for squamous carcinoma of the penis

PURPOSE: This retrospective study was performed to assess the treatment outcome and prognostic factors in 101 men with invasive squamous carcinoma of the penis treated at the Royal Marsden Hospital between 1960-1990. METHODS AND MATERIALS: The tumor was confined to the glans penis (T1) in 79 patients, 82 were node negative (N0), and two patients had distant metastases at presentation. The histology was Grade 1 (G1) in 36, Grade 2 (G2) in 18, Grade 3 (G3) in 28, and unknown in 19 patients. Node-positive disease was commoner in patients with G3 (p = 0.02) or T2/3/4 tumors (p = 0.007). Treatment for the primary tumor was external beam radiotherapy (EBRT) in 59, interstitial brachytherapy in 13, and partial or total penectomy in 29 patients. The median dose, dose/fraction, and treatment time for EBRT was 60 Gy, 2 Gy/fraction, and 46 days, respectively. Eighty patients received no inguinal node treatment, 13 had EBRT (4 with chemotherapy), and 8 underwent groin dissection at presentation. RESULTS: During a median follow-up of 5.2 years (2 months-22 years), 56 patients died (penile cancer 31, intercurrent illness 23 and unknown cause 2), giving 10 year overall and cause-specific survival (CSS) of 39 and 57%, respectively. Adverse prognostic factors for CSS on univariate analysis were G3, ulcerative/fungating or T2/3/ 4 tumors, node positive, Jackson's Stage 2/3/4, and surgical treatment for the primary. All but the last two were significant independent prognostic factors for CSS on multivariate analysis. Penile or perineal recurrence or residual disease after initial treatment was seen in 36 out of 98 evaluable patients, giving a 10-year local failure rate (LFR) of 45%. Local failure after initial treatment was successfully salvaged in the majority (26 out of 36) of patients with further surgery or radiotherapy, and local control was achieved ultimately in 74 out of 77 T1, 7 out of 12 T2; 3 out of 3 T3, and 3 out of 5 T4 tumors. In the 44 evaluable patients with T1 tumors treated by EBRT the only adverse RT parameter approaching prognostic significance (p = 0.052) was a BED value corrected for recovery of <60 Gy (alpha/beta 10, K = 0.5 Gy/day, mean = 21 days). CONCLUSION: Invasive squamous carcinomas of the penis carry a significant risk of loco-regional recurrence after initial radiotherapy and this can be successfully salvaged in most patients with further treatment. This mandates close follow-up to detect loco regional recurrence early.     

Fractionated high dose rate intraluminal brachytherapy in palliation of advanced esophageal cancer

PURPOSE: To optimize the dose of fractionated brachytherapy for palliation of advanced esophageal cancer. METHODS AND MATERIALS: One hundred and seventy-two patients with advanced esophageal cancer were randomized to receive 12 Gy/2 fractions (group A); 16 Gy/2 fractions (group B), and 18 Gy/3 fractions (group C) by high dose rate intraluminal brachytherapy (HDRILBT). Treatment was given weekly and dose prescribed at 1 cm from the source axis. Patients were followed up monthly and assessed for dysphagia relief and development of complications. RESULTS: Twenty-two patients died before completing treatment due to advanced disease and poor general condition. The overall survival was 19.4% at the end of 12 months for the whole group (A--9.8%, B--22.46%, C--35.32%; p > 0.05). The dysphagia-free survival was 28.9% at 12 months for the whole group (A--10.8%, B--25.43%, C--38.95%; p > 0.05). Forty-three patients developed fibrotic strictures needing dilatation (A--5 of 35, B--15 of 60, C--23 of 55; p = 0.032). Twenty-seven patients had persistent luminal disease (A--11, B--6, C--10), 15 of which progressed to fistulae (A--7, B--2, C--6; p = 0.032). There was no effect of age, sex, race, histology, performance status, previous dilation, presenting dysphagia score, presenting weight, grade, tumor length, and stage on overall survival, dysphagia-free, and complication-free survival (p > 0.05). On a multivariate analysis, brachytherapy dose (p = 0.002) and tumor length (p = 0.0209) were found to have a significant effect on overall survival; brachytherapy dose was the only factor that had an impact on local tumor control (p = 0.0005), while tumor length was the only factor that had an effect on dysphagia-free survival (p = 0.0475). When compared to other forms of palliation currently available (bypass surgery, laser, chemotherapy, intubation, external radiotherapy), fractionated brachytherapy gave the best results with a median survival of 6.2 months. CONCLUSIONS: Fractionated brachytherapy is the best modality for palliation of advanced esophageal cancer. It offers the best palliation to patient when compared to all other modalities currently available. The optimal brachytherapy dose ranges between 16 Gy in two fractions and 18 Gy in three fractions given a week apart.     

Comparison of stereotactic radiosurgery and brachytherapy in the treatment of recurrent glioblastoma multiforme

The purpose of this study was to compare the efficacy of stereotactic radiosurgery (SRS) and brachytherapy in the treatment of recurrent glioblastoma multiforme (GBM). The patients had either progressive GBM or pathologically proven GBM at recurrence after previous treatment for a lower grade astrocytoma. Thirty-two patients were treated with interstitial brachytherapy, and 86 received treatment with stereotactic radiosurgery (SRS). The patient characteristics were similar in the two groups. Those patients treated with SRS had a median tumor volume of 10.1 cm3 and received a median peripheral tumor dose of 13 Gy. Patients treated with brachytherapy had a median tumor volume of 29 cm3. Median dose to the periphery of the tumor volume was 50 Gy delivered at a median dose rate of 43 cGy/hour. Twenty-one patients (24%) treated with SRS were alive, with a median follow-up of 17.5 months. Median actuarial survival, measured from the time of treatment for recurrence, for all patients treated with SRS was 10.2 months, with survivals of 12 and 24 months being 45 and 19%, respectively. A younger age and a smaller tumor volume were predictive of better outcome. The tumor dose, the interval from initial diagnosis, and the need for reoperation were not predictive of outcome after SRS. Five patients (16%) treated with brachytherapy were alive, with a median follow-up of 43.3 months. The median actuarial survival for all patients treated with brachytherapy was 11.5 months. Survivals of 12 and 24 months were 44 and 17%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hypofractionated radiotherapy with concurrent 5-fluorouracil radiosensitisation for recurrent or locally advanced colorectal cancer. A phase II study

In a pilot study we treated 19 patients suffering from recurrent or locally advanced inoperable colorectal cancer, with concurrent hypofractionated radiotherapy (4-5 Gy/fraction, 2 fractions per week) and 5-fluorouracil bolus, 1 hour before RT at doses of 300 mg/m2. For 16 patients treated with radical intent the Normalised Total Dose for alpha/beta = 10 Gy ranged between 56-74 Gy (median 62 Gy). The schedule used was very well tolerated. Moderate grade II haematological toxicity was observed in 11% of cases and diarrhoea grade II/III resulting in 2-4 weeks treatment delay was observed in 26% of cases. One case with bowel perforation and one with painful subcutaneous fibrosis was observed during 12-27 months of follow-up. Out of 16 patients treated with radical intent 4 (25%) showed complete response and the overall response rate was 56% (9/16). The one-year symptom-free survival was obtained in 11/16 (69%) radically treated patients. It is concluded that hypofractionated radiochemotherapy with 5-fluorouracil for recurrent or locally advanced colorectal cancer is an effective regimen and has acceptable acute and late toxicity. Further investigation is required.     

Expression and immunogenicity in rats of recombinant adenovirus 5 DNA plasmids and vaccinia virus containing the HTLV-I env gene

PURPOSE: To evaluate the long-term disease control, survival and complication rates using high-dose-rate intracavitary brachytherapy (HDRB) and external beam radiotherapy (EBRT) for patients found to have isolated vaginal recurrences from early-stage endometrial adenocarcinoma following total abdominal hysterectomy and bisalpingo-oophorectomy (TAH BSO). MATERIALS AND METHODS: Twenty patients originally diagnosed with early-stage endometrial adenocarcinoma (FIGO stage I or II) following TAH BSO developed isolated vaginal recurrences and were referred to our radiation oncology department for definitive treatment. The median time between TAH BSO and vaginal recurrence was 24 months. Thirteen patients received combined modality treatment (EBRT + HDRB) and seven patients received HDRB only. Median prescribed dose was 4400 cGy by EBRT and 2400 cGy to the vagina mucosa surface by HDRB in the combined modality group. Median prescribed dose was 3500 cGy to the vagina mucosa surface for the HDRB only group. These patients were followed for a median duration of 47.5 months following treatment for isolated vaginal recurrence. RESULTS: Eighteen of 20 patients (90%) achieved a complete response to therapy and the remaining 2 achieved a partial response. Four of 18 complete responders developed a second recurrence within 30 months following radiotherapy. Ten-year cumulative local control rate was 74%. Ten-year cumulative cause specific and disease-free survival rate was 71 and 46%. Overall late complication rate was 15%; there were no grade 3 or 4 late complications. Three patients developed grade 2 late complications from treatment; all 3 were from the combined modality group (HDRB + EBRT). CONCLUSION: The use of HDRB resulted in high complete response rates and durable long-term disease-specific survival in a substantial percentage of patients. To our knowledge, this study represents the first published results on treatment of vaginal recurrences with HDRB. Although the number of patients in this study is small, treatment results compare favorably to those obtained from patients treated with low-dose-rate brachytherapy +/- EBRT from other studies.     

Molecular and pharmacological characterization of recombinant rat/mice N-methyl-D-aspartate receptor subtypes in the yeast Saccharomyces cerevisiae

PURPOSE: To assess the local control and survival in patients who received pelvic irradiation for locally recurrent rectal carcinoma. METHODS AND MATERIALS: The records of 519 patients with locally recurrent rectal carcinoma treated principally with external-beam radiation therapy between 1975 to 1985 at a single institute were retrospectively reviewed. These included 326 patients who relapsed locally following previous abdominoperineal resection, 151 after previous low anterior resection, and 42 after previous local excision or electrocoagulation for the primary. No patients had received adjuvant radiation therapy or chemotherapy for the primary disease. Concurrent extrapelvic distant metastases were found in 164 (32%) patients at local recurrence and, in the remaining 355, the relapse was confined to the pelvis. There were 290 men and 229 women whose age ranged from 23 to 91 years (median = 65). Median time from initial surgery to radiation therapy for local recurrence was 18 months (3-138 months). Radiation therapy was given with varying dose-fractionation schedules, total doses ranging from 4.4 to 65.0 Gy (median = 30 Gy) over 1 to 92 days (median = 22 days). For 214 patients who received a total dose > or = 35 Gy, radiation therapy was given in 1.8 to 2.5 Gy daily fractions. RESULTS: The median survival was 14 months and the median time to local disease progression was 5 months from date of pelvic irradiation. The 5-year survival was 5%, and the pelvic disease progression-free rate was 7%. Twelve patients remained alive and free of disease at 5 years after pelvic irradiation. Upon multivariate analysis, overall survival was positively correlated with ECOG performance status (p = 0.0001), absence of extrapelvic metastases (p = 0.0001), long intervals from initial surgery to radiation therapy for local recurrence (p = 0.0001), total radiation dose (p = 0.0001), and absence of obstructive uropathy (p = 0.0013). Pelvic disease progression-free rates were positively correlated with ECOG performance status (p = 0.0001), total radiation dose (p = 0.0001), and previous conservative surgery for the primary (p = 0.02). CONCLUSIONS: Survival is poor for patients who develop local recurrence following previous surgery for rectal carcinoma. Pelvic radiation therapy provides only short-term palliation, and future efforts should be directed to the use of effective adjuvant therapy for patients with rectal carcinoma who are at high risk of local recurrence.     

The radiotherapy of inoperable non-small-cell bronchial carcinoma. A retrospective analysis of 427 cases

BACKGROUND: The influence of tumor and patient characteristics on survival as well as acute normal tissue toxicity was retrospectively analyzed. PATIENTS AND METHODS: 427 patients with inoperable non-small cell lung cancer were retrospectively analyzed. Two thirds received a total dose of at least 70 Gy, and one third was irradiated with 60 to 66 Gy (2.0 to 2.5 Gy per fraction; split-course technique). 92% had a Karnofsky performance index of > or = 80%. Kaplan-Meier survival curves were generated and comparisons were made by the log-rank test. Prognostic factors were adjusted for by a proportional hazards analysis. RESULTS: Five-year survival rates (+/- SE) and the median survival times (95% confidence interval) were 2 +/- 2% and 11.1 months (9.1 ... 14.5) after 60 to 66 Gy; 8 +/- 2% and 14.9 months (13.3 ... 16.5) after 70+ Gy. The difference was significant in univariate (p = 0.0013) and multivariate analysis (p = 0.0006). Tumor stage (p = 0.0029: I + II > III; IIIA > IIIB) and gender (p = 0.0387: female > male patients) reached significance in multivariate analysis. Acute pneumonitis and esophagitis were observed in 11% and 9% of cases. CONCLUSIONS: Inoperable non-small cell lung cancer stage I to IIIA should be treated in a curative intention with total doses of about 70 Gy. This is feasible with acceptable normal tissue toxicity. Stage IIIB patients have a particular bad prognosis and should only be treated palliatively.     

Inoperable non-small cell lung cancer: a retrospective analysis of 427 patients treated with high-dose radiotherapy

PURPOSE: The influence of patient and treatment characteristics on survival as well as normal tissue toxicity were retrospectively analyzed. METHODS AND MATERIALS: Four hundred twenty seven patients with unresectable non-small cell lung cancer received at least 60 Gy and two-thirds were treated with 70 Gy. RESULTS: Five-year survival rates and median survival time (95% confidence interval) were 2 +/- 2% (mean +/- s.e.) and 11.1 months (9.1-14.5) after 60-66 Gy (median 60 Gy); 8 +/- 2% and 14.9 months (13.3-16.5) after > or = 70 Gy (p = 0.0013). Stage I-II patients had significantly higher survival rates as compared to Stage III patients (p = 0.0015). Within the subgroup of Stage III patients those with Stage IIIA had significantly higher survival rates than Stage IIIB (p = 0.0167). Female patients achieved 5-year survival rates after 70 Gy of 15 +/- 7% as compared to only 7 +/- 2% of their male counterparts. Chemotherapy, histology, Karnofsky status, and age had no influence on survival after univariate and multivariate analysis. Nine percent and 11% of the patients suffered from moderate to severe pneumonitis and esophagitis. CONCLUSION: High-dose radiotherapy of unresectable non-small cell lung cancer with total doses > 60 Gy conventionally fractionated is feasible. With doses of > or = 70 Gy significantly higher survival rates were achieved as compared to 60-66 Gy. Normal tissue toxicity was acceptable. For Stage IIIB patients, however, treatment results are disappointingly low even after 70 Gy with no 5-year survivor.     

Ten-year disease free survival after transperineal sonography-guided iodine-125 brachytherapy with or without 45-gray external beam irradiation in the treatment of patients with clinically localized, low to high Gleason grade prostate carcinoma

BACKGROUND: The authors report observed 10-year brachytherapy results in the treatment of 152 consecutive patients with clinically organ-confined prostate carcinoma. METHODS: One hundred and fifty-two consecutive patients with T1-T3, low to high Gleason grade, prostate carcinoma were treated between January 1987 and June 1988 at Northwest Hospital in Seattle, Washington. Their median age was 70 years (range, 53-92 years). Of these 152 patients, 98 (64%) received an iodine-125 implant alone (Group 1), and the remaining 54 patients (36%), who were judged to have a higher risk of extraprostatic extension, also were treated with 45 gray (Gy) of external beam irradiation to the pelvis (Group 2). No patient underwent lymph node sampling, and none received androgen ablation therapy. Multivariate regression and the Mann-Whitney rank sum test were used for statistical analysis. Preoperative patient data with associated success or failure outcomes at 10 years after treatment were used for training and validating a back-propagation neural network prediction program. RESULTS: The average preoperative prostate specific antigen (PSA) value, clinical stage, and Gleason grade were 11.0 ng/mL, T2, and 5, respectively. The median posttreatment follow-up was 119 months (range, 3-134 months). Overall survival 10 years after treatment was 65%. At last follow-up only 3 of the 152 patients (2%) had died of prostate carcinoma. Ninety-seven patients (64%) remained clinically and biochemically free of disease at 10 years of follow-up and had an average PSA value of 0.18 ng/mL (range, 0.01-0.5 ng/mL). In these patients a period of 42 months was required to reach the average PSA (0.5 ng/mL). The median to last PSA follow-up was 95 months (range, 3-134 months). Postoperative needle biopsies were negative in 56% of patients, positive in 15% of patients, and not available in 29% of patients. Only 6% of patients developed bone metastasis. At 10 years there was no statistically significant difference in treatment outcome between patients who received iodine-125 alone, and those who received iodine-125 with 45-Gy external beam irradiation (P = 0.08). Nevertheless, in these two groups preoperative PSA, stage, and Gleason grade were significantly different (P < 0.01). In the artificial neural network analysis, pretreatment serum PSA was the most accurate predictor of disease-free survival. CONCLUSIONS: Percutaneous prostate brachytherapy is a valid and efficient option for treating patients with clinically organ-confined, low to high Gleason grade, prostate carcinoma. Observed 10-year follow-up documents serum PSA levels superior to those reported in several published external beam irradiation series, and comparable to those published in a number of published radical prostatectomy series.     

Results of high-dose thoracic irradiation incorporating beam's eye view display in non-small cell lung cancer: a retrospective multivariate analysis

PURPOSE: To review the University of Michigan clinical experience in nonsmall cell lung cancer using high-dose thoracic irradiation (> or = 60 Gy) so that a starting dose for our prospective dose-escalation study could be determined. METHODS AND MATERIALS: Eighty-eight consecutive patients diagnosed with medically inoperable or locally advanced, unresectable nonsmall cell lung cancer were identified who were treated with thoracic irradiation alone to a minimum total dose of 60 Gy (uncorrected for lung density). All patients except four (95%) underwent computed tomography scanning for treatment planning that included beam's eye view display for tumor and critical structure localization. All patients were treated with standard fractionation in a continuous course to uncorrected total doses ranging from 60 to 74 Gy (median, 67.6 Gy). RESULTS: The median follow-up exceeds 24 months for all surviving patients (range, 12 to 78 months). The median survival time was 15 months, and the 2- and 3-year overall actuarial survival rates were 37% and 15%, respectively. Survival was significantly different between stage of disease (p = .004) and N-stage (p = .002) by univariate analysis. In a multivariate analysis, stage becomes the only characteristic significantly associated with outcome. The median time to local progression for 86 evaluable patients was 29 months. Stage (p = .0003), T-stage (p = .0095) and N-stage (p = .027) were significantly different with respect to local progression-free survival by univariate analysis. However, only stage was prognostic for local progression-free survival by multivariate analysis. There was no difference between large volume treatment (inclusion of the contralateral hilar and supraclavicular lymph nodes) and small volume treatment (exclusion of these elective nodal sites) with respect to local progression-free survival (p = .507) or survival (p = .520). With regard to dose, there was no significant difference between patients who received > 67.6 Gy and patients who received < or = 67.6 Gy with respect to local progression-free survival (p = .094) or survival (p = .142). Within the Stage III subgroup, local progression-free survival (p = .018) and survival (p = .061) were longer favoring the high-dose group of patients. Despite these doses, disease progression within the irradiated field was the predominant first site of treatment failure. CONCLUSION: This retrospective study has shown that it is feasible to deliver uncorrected tumor doses as high as 70 Gy using standard fractionation in NSCLC with acceptable morbidity. Local control remains a significant problem. These data indicate justification for a starting dose in a prospective radiation dose-escalation study.     

Intestinal lipid esterification and aging in mice and rats

BACKGROUND AND PURPOSE: The risk of side effects of low activity (i.e. <20 mCi) Iodine-125I (125I) interstitial radiotherapy was analyzed in patients with low-grade gliomas. MATERIALS AND METHODS: Permanent (247 patients) or temporary 125I-implants (268 patients) were used with a median reference dose of 60 Gy and 100 Gy, respectively, which was calculated to the outer rim of the tumour. The mean dose rate for temporary implants was low (median, 10 cGy/h). Risk factors were obtained from the multivariate proportional-hazards model. RESULTS: Radiogenic complications occurred in 39/515 patients (28 patients with transient symptoms and 11 patients with progressive symptoms). The most important risk factor was the volume of the intratumoural 200 Gy isodose. Available experimental data have associated a high dose zone in this range with the size of the treatment induced radionecrosis. Rapid tumour shrinkage (decrease of the tumour volume > or =50%) within the first 6 months with subsequent centripetal movement of non-pathologic tissue into the high dose zone and a reimplantation were additional risk factors. Radiation injury after rapid tumour shrinkage could be better avoided with temporary implants. A 200 Gy isodose volume <4.5 ml corresponded to an estimated risk of radiogenic complications <3%. There was a steep increase of the risk beyond this limit. Translation of the 200 Gy isodose volume in terms of the treatment volume and the reference dose allows rational treatment planning. The estimated risk of a temporary implant with an applied reference dose of 60 Gy and a treatment volume <23 ml was <3%. CONCLUSIONS: The intratumoural necrotizing effect of a low activity 125I implant limits its application to small treatment volumes. Radiation injury outside the treatment volume can be better avoided with temporary implants in the case of rapid tumour shrinkage.     

Short-course induction chemoradiotherapy with paclitaxel for stage III non-small-cell lung cancer

BACKGROUND: This study assessed toxicity, tumor response, disease control, and survival after short-course induction chemoradiotherapy and surgical resection in patients with stage III non-small-cell lung carcinoma. METHODS: Forty-five patients with stage III non-small-cell lung carcinoma received 12-day induction therapy of a 96-hour continuous infusion of cisplatin (20 mg/m2 per day), 24-hour infusion of paclitaxel (175 mg/m2), and concurrent accelerated fractionation radiation therapy (1.5 Gy twice daily) to a dose of 30 Gy. Surgical resection was scheduled for 4 weeks later. Postoperatively, a second identical course of chemotherapy and concurrent radiation therapy (30 to 33 Gy) was given. RESULTS: Induction toxicity resulted in hospitalization of 18 (40%) patients for neutropenic fever. No induction deaths occurred. Of 40 (89%) patients who underwent thoracotomy, resection for cure was possible in 32 (71%) patients. Pathologic response was noted in 21 (47%) patients, and 14 (31%) were downstaged to mediastinal node negative (stage 0, I, or II). At a median follow-up of 19 months, 24 patients were alive, 10 with recurrent disease. Of 21 deaths, 16 were from recurrent disease, three were from treatment, and two were unrelated. Recurrent disease was distant in 21 patients, distant and locoregional in 2, and locoregional in 3. The Kaplan-Meier projected 24-month survival is 49%. Projected 24-month survival is 61% for stage IIIA, 17% for stage IIIB (p = 0.035); 84% for pathologic responders, 22% for nonresponders (p<0.001); 83% for downstaged patients (stage 0, I, or II), 33% for those not downstaged (p = 0.005); and 63% for resectable patients, 14% for unresectable patients (p = 0.007). CONCLUSIONS: We conclude that short-course neoadjuvant therapy with paclitaxel (1) has manageable toxicity and a low treatment mortality, (2) results in good tumor response and downstaging, (3) provides excellent locoregional control with most recurrences being distant, and (4) has improved the median survival compared with historical controls. Survival was better in stage IIIA patients, resectable patients, pathologic responders, and patients downstaged to mediastinal node negative disease (stage 0, I, or II).     

三维适形放疗配合腔内后装治疗宫颈癌的临床研究

Objective: The aim of our study was to evaluate the outcome and complications of cervical cancer patients undergoing conventional intracavitary brachytherapy (ICBT) treated with 3D-conformal radiotherapy (3DCRT). Methods: Sixty cervical cancer patients were divided randomly into the conformal group and the conventional group. Thirty patients treated with 3D-conformal radiotherapy in the 3DCRT group, when the whole pelvic received DT 40 Gy, a planning CT scan of each patient was obtained and the second 3DCRT therapy plan was taken. Then, continued to irradiate to 50 Gy. At last, 3DCRT was boosted at local involved volumes to the total close of 60 Gy. When 3DCRT was combined with intracavitary brachytherapy, the dose of brachytherapy to point A was 30 Gy/5 fractions. In the conventional group, after a total tumor dose of 40 Gy was delivered by the whole pelvic irradiation, the four-field technique was used to irradiate the total pelvic and regional nodes (median close of 10 Gy), and the involved volumes were boosted to 60 Gy and the dose of brachytherapy to point A was 30 Gy-36 Gy/5-6 fractions. Moreover, both groups were combined with intracavitary brachytherapy respectively. Results: The 1, 2, 3-year survival rates for the 3DCRT group and the conventional group were 96.7%, 93.3%, 90.0% and 86.6%, 76.7%,70% respectively (P = 0.04, P = 0.02 and P = 0.02). There was a statistically significant difference between the two groups.Compared to the two groups each other in toxic effects, except for the Ⅰ-Ⅱ grade rectal and bladder reaction and pelvic fibrosis which was lower in the 3DCRT group (P = 0. 007, P = 0. 006 and P = 0. 015), the side effects were similar and well tolerated in two groups. Conclusion: The all-course 3DCRT combined with intracavitary brachytherapy can be considered as an effective and feasible approach to cervical cancer and may significantly improve the survival rate and reduce the late toxicity. This new rote for 3DCRT merits need further evaluation with large patient numbers and longer follows up.