Importance of post-implant dosimetry in permanent prostate brachytherapy

OBJECTIVE: Post-implant dosimetry has become the gold standard for implant evaluation and it is recommended that it be performed on all patients undergoing prostate brachytherapy. The technique, results and correlation with clinical outcomes will be presented. METHODS: The method and outcomes of post-implant dosimetry are explored by outlining the experience at the Mount Sinai Medical Center, New York, as well as reviewing the literature. The most accurate time to perform post-implant dosimetry is 1 month after implant. Computed tomography (CT)-based dosimetry is currently the best available technique for performing this analysis. The technique involves taking 3-mm abutting CT slices throughout the implanted area. The prostate and normal structures are outline on the CT slices. These structures are recreated in three dimensions. Dose volume histograms (DVH) are created and allow the dose to these organs to be quantified. RESULTS: The relationship between dosimetric findings and clinical outcomes has been established. The dose delivered to 90% of the prostate on DVH (D90) has been correlated to prostate-specific antigen (PCA) control and post-treatment biopsy results. D90 values of >or=140Gy have been associated with improved biochemical control and lower positive post-treatment biopsy results. Doses derived from the dosimetric analysis to prostate, urethra and rectum have been correlated with the development of acute and chronic urinary morbidity, sexual potency and rectal morbidity. Future initiatives involve performing dosimetric calculations intraoperatively at the time of the implant. CONCLUSIONS: Post-implant CT-based dosimetry is an essential component of prostate brachytherapy. It is the only method of assessing the actual dose delivered to the prostate and normal surrounding structures. Future development in post-implant and intraoperative dosimetry will continue to improve permanent prostate brachytherapy as a safe an effective treatment for prostate cancer.     

Commentary on “Toxicity after external beam radiotherapy for prostate cancer: An analysis of late morbidity in men with diabetes mellitus.” Kalakota K,Liauw SL,Department of Radiation Oncology,Northwestern Memorial Hospital,Chicago, IL.: Urology 2013;81(6):1196–201. doi: 10.1016/j.urology.2013.01.047. [Epub 2013 Mar 26]

ObjectiveTo investigate the influence of diabetes mellitus (DM) on late genitourinary (GU) and gastrointestinal (GI) toxicity in patients treated with external beam radiotherapy (RT) for prostate cancer.Materials and methodsA total of 626 men were treated with curative-intent RT for prostate cancer from 1988 to 2008. Using the National Comprehensive Cancer Network risk category, the patients were considered to have low-risk (30%), intermediate-risk (42%), or high-risk (28%) prostate cancer. The median radiation dose was 74 Gy; 45% received androgen deprivation therapy for a median of 4 months. Late GU and GI Radiation Therapy Oncology Group toxicity was recorded prospectively at each visit after external beam RT. The median follow-up period was 55 months.ResultsOf the 626 men, 102 (16%) had DM that was controlled by diet (8%), oral medications (52%), or insulin (39%). The patients with DM were more likely to receive intensity-modulated RT and androgen deprivation therapy and to have a shorter follow-up duration (P≤.05 for all). Univariate analyses demonstrated that greater radiation dose, baseline urinary dysfunction, intensity-modulated RT, and DM were associated with grade 2 or greater GU toxicity, and transurethral resection of the prostate and DM were associated with grade 3 or greater GU toxicity. In addition, androgen deprivation therapy use, age≥70 years, and anticoagulation were associated with grade 2 or greater GI toxicity, and age≥70 years and anticoagulation were associated with grade 3 or greater GI toxicity. The multivariate analyses for late toxicity demonstrated a greater risk of grade 2 or greater (relative risk 1.36, P = .10) and grade 3 or greater GU toxicity (relative risk 2.74, P = .04) with DM.ConclusionA greater incidence of late GU toxicity was seen in patients with DM treated for prostate cancer. This relationship might be useful when considering the treatment of patients with DM, especially those receiving dose-escalated RT or with a history of transurethral resection of the prostate.     

Seed localization and TRUS-fluoroscopy fusion for intraoperative prostate brachytherapy dosimetry.

OBJECTIVE: To develop and evaluate an integrated approach to intra-operative dosimetry for permanent prostate brachytherapy (PPB) by combining a fluoroscopy-based seed localization routine with a transrectal ultrasound (TRUS)-to-fluoroscopy fusion technique. MATERIALS AND METHODS: Three-dimensional seed coordinates are reconstructed based on the two-dimensional seed locations identified from three fluoroscopic images acquired at different angles. A seed-based registration approach was examined in both simulation and phantom studies to register the seed locations identified from the fluoroscopic images to the TRUS images. Dose parameters were then evaluated and compared to CT-based dosimetry from a patient dataset. RESULTS: Less than 0.2% error in the D90 value was observed using the TRUS-fluoroscopy image-fusion-based method relative to the CT-based post-implantation dosimetry. In the phantom study, an average distance of 3 mm was observed between the seeds identified from TRUS and the reconstructed seeds at registration. Isodose contours were displayed superimposed on the TRUS images. CONCLUSIONS: Promising results were observed in this preliminary study of a TRUS-fluoroscopy fusion-based brachytherapy dosimetry analysis method, suggesting that the method is highly sensitive and calculates clinically relevant dosimetry, including the prostate D90. Further validation of the method is required for eventual clinical application.     

Organ-confined prostate cancer: treatment with high doses of radioterapy (intensity modulated radiotherapy)

PurposeTo report toxicity and local control in patients with localized prostate cancer, treated with high dose radiotherapy.Materials and methodsThe records of 100 consecutive patients with clinically localized prostate cancer treated between june 2003 and may 2006 were reviewed. They received 80 Gy to the target volume with a biphasic technique (3DCRT + IMRT). The median pretreatment PSA was 9. The median follow-up time was 12 months.ResultsEighteen (18%) developed acute Grade 2 rectal toxicity, and no patient experienced acute grade 3 or higher rectal symptoms. Forty-four (44%) developed acute Grade 2 urinary symptoms while 34% of the patients experienced no GU symptoms (Grade 0) during treatment. Three patients (3%) developed late rectal toxicity grade 2 and eight patients (8%) experienced late urinary toxicity grade 2; any patients experienced more severe symptoms.We recorded biochemical relapse in two patients, both had poor prognostic factors at initial diagnosis of prostate cancer.ConclusionsThe data demonstrate the feasibility and safety of high dose radiotherapy for patients with localized prostate cancer and provide a proof that this method allow safe dose escalation with low severe toxicities to the normal tissues.     

A new model using number of needles and androgen deprivation to predict chronic urinary toxicity for high or low dose rate prostate brachytherapy

PURPOSE: Prostate brachytherapy is an established treatment modality in early stage prostate cancer. We retrospectively reviewed our experience with low dose rate (LDR) and high dose rate (HDR) brachytherapy as a single treatment modality for early prostate cancer with emphasis on chronic toxicity.MATERIALS AND METHODS: From June 1996 to August 2003, 253 patients with stage II prostate cancer, prostate specific antigen less than 12 and Gleason score less than 7 were treated with brachytherapy alone at our institution. A total of 92 patients underwent HDR brachytherapy with 192Ir, while 161 underwent LDR brachytherapy with 103Pd. HDR minimum prostate dose was 38 Gy, delivered in 4 fractions with a single implant during 36 hours. For HDR we used real-time dynamic 3-dimensional ultrasound base dosimetry. For 103Pd seed implants the dose was 120 Gy using selective peripheral weighted dose distribution. Treatment was given based on patient preference after pretreatment transrectal ultrasound. Toxicity was scored using the National Cancer Institute Common Toxicity Criteria 2.0. Median followup in all 253 cases was 2.9 years.RESULTS: In all patients the rate of 3-year urinary toxicity grade 2 or greater and grade 3 or greater was 26% and 6.9%, which was not significantly different between HDR and LDR (p = 0.3 and 0.4, respectively). However, grade 1 urogenital toxicity was lower for HDR (p = 0.002). The 3-year grade 2 rectal toxicity rate was 0.8% with no grade 3 or greater events, which was and similar in the HDR and LDR groups (1% and 0.6%, respectively). No cancer related deaths occurred and 4-year overall survival was 99% for HDR and 96.4% for LDR (p = 0.4). The 3-year American Society for Therapeutic Radiology and Oncology biochemical control rate was 90% for LDR and 93% for HDR. Cox multivariate analysis for grade 2 or greater urinary toxicity was significant for the use of 14 or greater needles (HR 6.1, p = 0.02) and hormonal therapy (HR 2.2, p = 0.02). In the absence of risk factors the 4-year grade 2 or greater urinary toxicity rate was 7% vs 65% if the 2 risk factors were present (p <0.001). Impotence crude rates were 18.3% for HDR and 41.3% for LDR (p = 0.002).CONCLUSIONS: HDR and LDR chronic urinary toxicity grade 2 or greater rates were equivalent. However, grade 1 was lower for HDR. The impotence rate was decrease by half with HDR. Neoadjuvant hormonal therapy and 14 or greater needles were significantly associated with increased chronic urinary toxicity on multivariate analysis.     

Evolution of toxicity after conformal radiotherapy for prostate cancer

The limiting factor for radiation (RT) dose-escalation is normal tissue toxicity. In dose-escalation studies, it is important to determine the factors associated with toxicity and the length of follow-up period after which a particular RT dose is considered safe. We analyzed 449 prostate cancer patients treated with RT at our institution and followed for a median of 27 months. Genitourinary (GU) and gastrointerological (GI) complications were graded and analyzed using three different statistical models. Univariate and multivariate analyses were conducted for factors associated with toxicity. There was no RTOG grade 4 or 5 toxicity. Only 23 patients (5%) experienced grade 3 toxicity. After treatment, there was an initial rapid decline in the risk of toxicity following treatment, followed by an increase or stabilization of the toxicity with time of follow-up. The breakpoints between the two periods were 2 y (any toxicity) and 1 y (high toxicity) for GU and 9 months (any toxicity, high toxicity) for GI. Age, dose, fraction size, duration of treatment and hospital of treatment emerge as important factors in the probability of developing toxicity. Our study shows that delivering conventional doses using conformal techniques is associated with minimal high-grade toxicity. However, even within a narrow dose range and fraction size used, differences do emerge which should lead one to be cautious in extending the results of dose escalation study to the community practice without a sufficient follow-up.     

High dose rate brachytherapy as a boost for the treatment of localized prostate cancer

PURPOSE: We report the outcome and toxicities of high dose rate brachytherapy as a boost for localized prostate cancer. MATERIALS AND METHODS: Between 1996 and 2003, 309 patients with prostate carcinoma were treated with external beam radiation therapy and high dose rate brachytherapy. Furthermore, 36% of the patients received neoadjuvant/concurrent or adjuvant androgen deprivation therapy. Patients were stratified into 3 groups. Group 1 of 67 patients had Gleason score 6 or less, pretreatment prostate specific antigen 10 ng/ml or less and clinical stage T2a or less. Group 2 of 109 patients had Gleason score 7 or greater, pretreatment prostate specific antigen greater than 10 ng/ml and clinical stage T2b or greater. Group 3 of 133 patients had 2 or more of these higher risk factors. RESULTS: At a median followup of 59 months the 5-year biochemical control rate, as defined by the American Society for Therapeutic Radiation and Oncology, was 86%, cause specific survival was 98% and overall survival was 91%. Biochemical control in stratified groups 1 to 3 was 98%, 90% and 78%, respectively. On univariate analysis risk group, pretreatment prostate specific antigen and Gleason score were significant predictors of biochemical control. However, on multivariate analysis only risk group and pretreatment prostate specific antigen were significant. Using the Common Toxicity Criteria scale there were 2 cases of grade 3 acute urinary toxicity. Regarding late side effects 4% of patients had grade 3 genitourinary toxicity and 1 had a grade 4 rectal complication. CONCLUSIONS: External beam radiation therapy and high dose rate brachytherapy for prostate cancer resulted in excellent biochemical control, cause specific survival and overall survival with minimal severe acute or late complications.     

Technical acquisition and dosimetric assessment of iodine-125 permanent brachytherapy in localized prostate cancer: Our first series of 100 patients

Objectives:   To assess our initial experience in the treatment of localized prostate cancer using low-dose-rate brachytherapy (LDR-brachytherapy) with iodine-125.
Methods:   One-hundred consecutive patients received LDR-brachytherapy between July 2004 and October 2006. Seventy-six patients were treated with seed implantation alone, whereas 24 patients were treated with a combination of brachytherapy and external beam radiotherapy. The minimal percentage of the dose received by 90% of the prostate gland (%D90), the percentage prostate volume receiving 100% of the prescribed minimal peripheral dose (V100), and the operation time were compared among every 10 consecutive patients.
Results:   The means of %D90 and V100 were 109.6% and 93.4%, respectively. When compared with the first 10 patients, both D90 and V100 showed significant improvement in the following 10 consecutive patients. Similarly, the mean operation time decreased significantly according to the accumulated number of patients.
Conclusions:   Our initial experience with the first 100 cases suggests that LDR-brachytherapy needs accumulation of many more patients to obtain high-quality post-implant dosimetric outcomes.     

Patterns and Predictors of Amelioration of Genitourinary Toxicity After High-dose Intensity-modulated Radiation Therapy for Localized Prostate Cancer: Implications for Defining Postradiotherapy Urinary Toxicity

Background

Treatment-related toxicity and quality of life (QoL) considerations are important when counseling patients with localized prostate cancer (PCa).

Objective

To determine the incidence and longitudinal pattern of late genitourinary (GU) toxicity and QoL after high-dose, intensity-modulated radiotherapy (IMRT).

Design, setting, and participants

A total of 268 patients with localized PCa were treated between June 2004 and December 2008 at a tertiary referral center. Median follow-up was 5 yr (range: 3–7.7 yr).

Intervention

Patients underwent IMRT to a total dose of 86.4 Gy; 50% of patients underwent neoadjuvant and concurrent androgen-deprivation therapy.

Outcome measurements and statistical analysis

Patients were evaluated with the prospectively obtained International Prostate Symptom Score (IPSS) questionnaire. GU toxicity was also scored using the Common Terminology Criteria for Adverse Events (CTCAE) v.4.0; toxicity events were defined as increase over baseline. Differences in increases in IPSS sums and QoL index between baseline IPSS sum and QoL index groups were analyzed using the Kruskal-Wallis and Mann-Whitney tests. Univariate and multivariate Cox regression models were applied.

Results and limitations

The overall median IPSS sum increase during follow-up was 3 and was less pronounced among patients with severe baseline symptoms compared with those with mild baseline symptoms (median increase: 0 vs 4; p < 0.0001). Overall QoL index was unchanged after IMRT but appeared to improve in patients with dissatisfied baseline QoL compared with satisfied baseline QoL (p < 0.0001). Fifty-five (20%) and 2 (1%) patients developed grade 2 and 3 late GU toxicities, respectively; however, in 28 of 57 patients (49%), toxicity resolved during follow-up. Even though the IPSS data were prospectively obtained, most patients were not treated within a prospective protocol.

Conclusions

Late GU toxicity after high-dose IMRT was mild; severe, late GU toxicity was rare. Changes in IPSS sum and QoL index were dependent on the baseline GU function, which might be useful for future patient counseling.     

Radioimmunotherapy of prostate cancer in human xenografts using monoclonal antibodies specific to prostate specific membrane antigen (PSMA): studies in nude mice

BACKGROUND: Prostate specific membrane antigen (PSMA), expressed by virtually all prostate cancers is an ideal target for targeted therapy of prostate cancer. Radiolabeled J591 monoclonal antibody (MAb) binds with high affinity to an extracellular epitope of PSMA and localizes specifically in PSMA positive LNCaP tumors in vivo. METHODS: Pre-clinical radioimmunotherapy (RIT) studies using (131)I-huJ591 and (90)Y-1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid (DOTA)-huJ591 MAbs were studied in nude mice bearing LNCaP xenografts. RESULTS: A 15-90% reduction in mean tumor volume was observed after a single dose of (131)I-huJ591 (3.7-11.1 MBq) or (90)Y-DOTA-huJ591 (3.7-7.4 MBq). The median survival time increased 2-3 times relative to untreated controls. Multiple administrations of fractionated doses of (90)Y-DOTA-huJ591 were even more effective with minimal toxicity. Radiation dose to blood and tumor was higher with (90)Y than with (131)I. The maximum tolerated dose (MTD) is 5.55 MBq for (90)Y-DOTA-huJ591 and more than 11.1 MBq for (131)I-huJ591. For (90)Y-DOTA-huJ591 at MTD, dose to the tumor was 2,753 cGy. CONCLUSIONS: In nude mice bearing PSMA positive tumors, radiation dose to the tumor with (90)Y-DOTA-J591 is greater for large tumors than with (131)I-J591. The theoretical and practical considerations strongly suggest that (90)Y-DOTA-huJ591 may be a suitable radiopharmaceutical for the treatment of prostate cancer.     

Locally advanced prostate cancer treated with concomitant radiation and 5-fluorouracil: Southwest Oncology Group Study 9024

PURPOSE: Radiation is considered the standard treatment for locally advanced (T3 and T4) prostate cancer but cure with radiation alone is infrequent. Studies have shown that adding androgen ablation improves the results but there is still much room for improvement. We performed a phase II multi-institutional study to explore the feasibility of concomitant chemoradiotherapy. MATERIALS AND METHODS: Eligible patients had prostate cancer with clinical evidence of invasion through the prostatic capsule or into the seminal vesicles without evidence of nodal or distant metastasis. Prior prostatectomy was not allowed and patients could not be candidates for surgical resection due to medical reasons or refusal of surgery. Radiation consisted of 7,020 cGy in 39 fractions. Continuous infusion 5-fluorouracil at a dose of 200 mg/m2 daily was started on day 1 and continued 7 days weekly until the last day of radiation. RESULTS: All 30 eligible patients were evaluated for toxicity. Diarrhea was the most common toxicity with grade 3 and 4 diarrhea in 2 and 1 patients, respectively. The only other grade 4 toxicity was hemorrhagic cystitis in 1 patient. There was 1 incident each of grade 3 stomatitis, congestive heart failure, edema, proctitis and hematuria. No patient with grade 3 or 4 toxicity required treatment delay. Ten patients (33%) achieved a negative biopsy and 13 (43%) achieved prostate specific antigen less than 1.0 ng/ml. Six patients (20%) achieved a complete response, defined as negative biopsy and prostate specific antigen less than 1.0 (95% CI 8 to 39). Patients without any biopsies or without prostate specific antigen followup were assumed to be nonresponders. CONCLUSIONS: Toxicity was acceptable. The modest response rate indicates that better chemotherapy that improves local and systemic failure is necessary to improve the results. This study confirms the feasibility of a combined chemoradiotherapy approach.     

Toxicity following high-dose salvage radiotherapy after radical prostatectomy

OBJECTIVE: To assess gastrointestinal (GI) and genitourinary (GU) toxicity in patients treated with salvage radiotherapy (SRT) at doses of 70.2 Gy after radical retropubic prostatectomy (RRP). PATIENTS AND METHODS: Medical records were reviewed retrospectively to identify patients treated with SRT after RRP between January 1999 and December 2005. Of the 62 patients identified, 30 were included for analysis. GI and GU toxicity was assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events and the American Urological Association Symptom Index (AUASI), respectively. RESULTS: The median AUASI score of the 17 patients with scores before SRT was 4, of the 24 with scores after SRT was 6, and of the 15 with scores before and after SRT the median increase was 3. Of the 29 patients with GI toxicity data, nine (31%) had diarrhoea after SRT (three after <70.2 Gy and six after 70.2 Gy). In all cases, the diarrhoea was mild (grade 1). Of all patients, 12 (41%) had proctitis after SRT (four after <70.2 Gy and eight after 70.2 Gy); the proctitis was grade 1 in four and grade 2 in eight, with no cases of grade 3 proctitis. There was no statistically significant difference in the median change in AUASI scores and GI toxicity incidence between patients receiving <70.2 or 70.2 Gy of SRT. CONCLUSION: High-dose SRT (70.2 Gy) is generally well tolerated with acceptable low-grade GI toxicity and minimal changes in AUASI scores.     

The efficacy and safety of hypofractionated radiotherapy with concurrent anti‐HER‐2 therapy following breast‐conserving therapy for breast cancer

The purpose of this study was to report rates and severities of radiation‐related toxicities and analyze disease‐control outcomes in patients who have received hypofractionated whole breast radiation (HF) with concurrent trastuzumab with or without pertuzumab. We conducted a retrospective cohort study including women with stage I‐III HER2‐positive breast cancer who received HF at the University of Pennsylvania between 1/2005 and 5/2018 with concurrent trastuzumab with or without pertuzumab. Fractionation was 266 cGy daily to a total dose of 4256 cGy with or without a sequential tumor bed boost. Eighty patients were included in the cohort with a median follow‐up time of 21.44 months. There was one grade 3 acute toxicity (fatigue) and no grade 3 late toxicities. 91% and 25% of patients experienced grade 1‐2 acute and late skin reactions, respectively. An excellent‐good cosmetic outcome was reported by 74% and 95% of patients and physicians, respectively. No patients experienced tumor recurrences, and the only death was due to a secondary cause. These results suggest that hypofractionated whole breast radiation administered concurrently with anti‐HER‐2 therapies is efficacious and has acceptable toxicity in early‐stage breast cancer patients treated with lumpectomy. Continued follow‐up is warranted to evaluate long‐term outcomes.     

Application of thermoplastic elastomer (TPE) bolus in postmastectomy radiotherapy

PurposeTo assess the planned dose, in vivo dosimetry, acute skin toxicity, pain, and distress using Thermoplastic Elastomer (TPE) bolus for postmastectomy radiotherapy (PMRT).Material and methodsThirty-two PMRT patients with TPE bolus (17 patients for 25 fractions, 15 patients for the first 20 fractions) were selected for the study. The acute skin toxicity, pain, and psychological distress were assessed from the first treatment week to the fourth week after the end of treatment. At the first treatment, the MOSFET was used in vivo dosimetry measurement.ResultsIn vivo dosimetry with the bolus, the dose deviation ranged from −6.22% to −1.56% for 5 points. The presence of grade 1 and 2 skin toxicity reached its peak (70.0% and 13.3%) in the sixth week. Two patients (6.6%) with 25 fractions bolus experienced moist desquamation in the fifth and seventh week, with pain score 2 and 3, and interruptions of 3 and 5 days, respectively. The incidence of pain score 1, 2, and 3 peaked in the fifth (33.3%), fourth (33.3%), and seventh (10.0%) week. No patients experienced grade 3 skin toxicity and severe pain. One patient had significant anxiety, and two patients had significant depression.ConclusionThe TPE bolus can accurately fit skin and improve the surface dose to more than 90%. Twenty fractions with TPE bolus had similar skin toxicity and pain to those without bolus and did not increase patients' distress and clinical workload, compared with the literature's data, which is an alternative to the 3D printing bolus for PMRT.     

Combination chemotherapy with paclitaxel,estramustine and carboplatin for hormone refractory prostate cancer

PURPOSE: The activity of estramustine phosphate is synergistic with paclitaxel against hormone refractory prostate cancer. Moreover, the single agent activity of carboplatin has demonstrated a 17% response rate in measurable disease. Therefore, we conducted a prospective trial to establish more effective chemotherapy consisting of paclitaxel, estramustine phosphate and carboplatin for hormone refractory prostate cancer. MATERIALS AND METHODS: The study included 32 patients with hormone refractory prostate cancer. Prior chemotherapy was accepted. Patients were treated with 100 mg./m.2 paclitaxel intravenously weekly, 10 mg./kg. estramustine phosphate orally daily and carboplatin intravenously to an area under the curve of 6 on day 1 of every 4-week cycle. Treatment was continued until disease progression or excessive toxicity. RESULTS: Of the 32 patients 30 were assessable for response. A median of 7 consecutive cycles was administered per patient. Ten patients had received prior cytotoxic chemotherapy. Levels of prostate specific antigen decreased by greater than 50% in 100% of patients and by greater than 90% in 56.7%. Partial response was obtained in 61.1% of measurable lesions. Consumption of medication for cancer induced pain was reduced in 89.5% of patients. Tumor volume reduction and/or antitumor therapeutic effects were exhibited in 81.0% of patients with positive biopsy. At a median followup of 48 weeks median time to progression was 48 weeks and median overall survival was 95 weeks. Two patients suffered myocardial infarction and hepatic insufficiency, respectively, and discontinued treatment during the first cycle. Major toxicities were grade 3 or 4 anemia in 59.4% of patients, leukopenia in 37.5%, thrombocytopenia in 28.1% and neuropathy in 12.5%. However, all toxicity was temporary and reversible with dose reduction or temporary cessation of chemotherapeutic agents. CONCLUSIONS: Paclitaxel, estramustine phosphate and carboplatin chemotherapy was extremely effective for hormone refractory prostate cancer. Although hematological and neurotoxicity were modest, this therapy may be more manageable with lower doses.     

High-dose superselective intra-arterial cisplatin and concomitant radiation (RADPLAT) for advanced head and neck cancer

BACKGROUND: The purpose of this study was to study the effect of intensive targeted chemoradiation in a group of patients with head and neck cancer with stage IV inoperable disease. METHODS: We examined 79 patients with inoperable stage IV head and neck cancer receiving intra-arterial infusion of high-dose cisplatin (150 mg/m(2)) on days 2, 9, 16, and 23 concomitant with delivery of external beam radiotherapy (total dose, 70 Gy; 2 Gy, 35 fractions; 1 fraction/day for 7 weeks). Sodium thiosulfate was administered intravenously to provide effective cisplatin neutralization. RESULTS: Four patients were not assessable. Complete local tumor response was achieved in 72 patients (91%) and a partial response in three patients. The complete response rate of neck node metastases was 90%. The 1- and 2-year locoregional control rates were 82% and 69%, respectively. The median overall survival time was 2.2 years, with a 3-year overall survival probability of 43%. Acute toxicities were as follows: grade III/IV hematologic toxicity (22%/16%), grade III/IV nephrotoxicity (0%), grade III mucositis (43%), grade III skin reactions (24%), grade III toxicity of the upper gastrointestinal tract (57%), grade III nausea (20%), and grade III subjective hearing loss (10%). Grade V toxicity (treatment-related deaths) was 3.8%. Six (18%) of 33 patients with complete remission needed tube feeding 2 years after treatment without intercurrent salvage surgery. CONCLUSIONS: Supradose superselective intra-arterial cisplatin and concomitant radiation is an effective organ-preserving therapy in an unfavorable group of patients. Our series confirms encouraging results reported previously. This regimen is justified in unresectable patients despite the substantial toxicity.