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Biomedical subjects

P C Koper

Publications and source records attributed to P C Koper.

At least 19 recordsLinked to original sources
PubMed2001

The morbidity of treatment for patients with Stage I endometrial cancer: results from a randomized trial.

PURPOSE: To compare the treatment complications for patients with Stage I endometrial cancer treated with surgery and pelvic radiotherapy (RT) or surgery alone in a multicenter randomized trial. METHODS AND MATERIALS: The Postoperative Radiation Therapy in Endometrial Carcinoma (PORTEC) trial included patients with endometrial cancer confined to the uterine corpus, either Grade 1 or 2 with more than 50% myometrial invasion, or Grade 2 or 3 with less than 50% myometrial invasion. Surgery consisted of an abdominal hysterectomy and oophorectomy, without lymphadenectomy. After surgery, patients were randomized to receive pelvic RT (46 Gy), or no further treatment. A total of 715 patients were randomized. Treatment complications were graded using the French-Italian glossary. RESULTS: The analysis was done at a median follow-up duration of 60 months. 691 patients were evaluable. Five-year actuarial rates of late complications (Grades 1-4) were 26% in the RT group and 4% in the control group (p < 0.0001). Most were Grade 1 complications, with 5-year rates of 17% in the RT group and 4% in the control group. All severe (Grade 3-4) complications were observed in the RT group (3%). Most complications were of the gastrointestinal tract. The symptoms resolved after some years in 50% of the patients. Grade 1-2 genitourinary complications occurred in 8% of the RT patients, and 4% of the controls. Bone complications occurred in 4 RT patients (1%). Seven patients (2%) discontinued their RT due to acute RT-related symptoms. Patients with acute morbidity had an increased risk of late RT complications (p = 0.001). The 4-field box technique was associated with a lower risk of late complications (p = 0.06). CONCLUSION: Pelvic RT increases the morbidity of treatment in Stage I endometrial cancer. In the PORTEC trial, severe complications occurred in 3% of treated patients, and over 20% experienced mild (mostly Grade 1) symptoms. Patients with acute RT-related morbidity had an increased risk of late complications. As pelvic RT in Stage I endometrial carcinoma was shown to significantly reduce the rate of locoregional recurrence, but without a survival benefit, its use in the adjuvant setting requires careful patient selection (treating those at increased risk of relapse), and the use of treatment schemes with the lowest risk of morbidity.

Aged↗
PubMed2001

Sildenafil citrate (Viagra) and erectile dysfunction following external beam radiotherapy for prostate cancer: a randomized, double-blind, placebo-controlled, cross-over study.

PURPOSE: To determine the efficacy of sildenafil citrate (Viagra) in patients with erectile dysfunction after three-dimensional conformal external beam radiotherapy (3D-CRT) for prostate cancer. METHODS AND MATERIALS: 406 patients with complaints of erectile dysfunction and who completed radiation at least 6 months before the study were approached by mail. 3D-CRT had been delivered (mean dose 68 Gy). Sixty patients were included and entered a double-blind, placebo-controlled, cross-over study lasting 12 weeks. They received during 2 weeks 50 mg of sildenafil or placebo; at Week 2 the dose was increased to 100 mg in case of unsatisfactory erectile response. At Week 6, patients crossed over to the alternative treatment. Data were collected using the International Index of Erectile Function (IIEF) questionnaire, and side effects were recorded. RESULTS: Mean age was 68 years. All patients completed the study. For most questions of the IIEF questionnaire there was a significant increase in mean scores from baseline with sildenafil, but not with placebo. Ninety percent of the patients needed a dose adjustment to 100 mg sildenafil. Side effects were mild or moderate. CONCLUSION: Sildenafil is well tolerated and effective in improving erectile function of patients with ED after 3D-CRT for prostate cancer.

Aged↗
PubMed2000

Surgery and postoperative radiotherapy versus surgery alone for patients with stage-1 endometrial carcinoma: multicentre randomised trial. PORTEC Study Group. Post Operative Radiation Therapy in Endometrial Carcinoma.

BACKGROUND: Postoperative radiotherapy for International Federation of Gynaecology and Obstetrics (FIGO) stage-1 endometrial carcinoma is a subject of controversy due to the low relapse rate and the lack of data from randomised trials. We did a multicentre prospective randomised trial to find whether postoperative pelvic radiotherapy improves locoregional control and survival for patients with stage-1 endometrial carcinoma. METHODS: Patients with stage-1 endometrial carcinoma (grade 1 with deep [> or =50%] myometrial invasion, grade 2 with any invasion, or grade 3 with superficial [<50%] invasion) were enrolled. After total abdominal hysterectomy and bilateral salpingo-oophorectomy, without lymphadenectomy, 715 patients from 19 radiation oncology centres were randomised to pelvic radiotherapy (46 Gy) or no further treatment. The primary study endpoints were locoregional recurrence and death, with treatment-related morbidity and survival after relapse as secondary endpoints. FINDINGS: Analysis was done according to the intention-to-treat principle. Of the 715 patients, 714 could be evaluated. The median duration of follow-up was 52 months. 5-year actuarial locoregional recurrence rates were 4% in the radiotherapy group and 14% in the control group (p<0.001). Actuarial 5-year overall survival rates were similar in the two groups: 81% (radiotherapy) and 85% (controls), p=0.31. Endometrial-cancer-related death rates were 9% in the radiotherapy group and 6% in the control group (p=0.37). Treatment-related complications occurred in 25% of radiotherapy patients, and in 6% of the controls (p<0.0001). Two-thirds of the complications were grade 1. Grade 3-4 complications were seen in eight patients, of which seven were in the radiotherapy group (2%). 2-year survival after vaginal recurrence was 79%, in contrast to 21% after pelvic recurrence or distant metastases. Survival after relapse was significantly (p=0.02) better for patients in the control group. Multivariate analysis showed that for locoregional recurrence, radiotherapy and age below 60 years were significant favourable prognostic factors. INTERPRETATION: Postoperative radiotherapy in stage-1 endometrial carcinoma reduces locoregional recurrence but has no impact on overall survival. Radiotherapy increases treatment-related morbidity. Postoperative radiotherapy is not indicated in patients with stage-1 endometrial carcinoma below 60 years and patients with grade-2 tumours with superficial invasion.

Adenocarcinoma↗
PubMed2000

Detection of internal organ movement in prostate cancer patients using portal images.

Previous research has indicated that the appearance of large gas pockets in portal images of prostate cancer patients might imply internal prostate motion. This was verified with simulations based on multiple computed tomography (CT) data for 15 patients treated in supine position. Apart from the planning CT scan, three extra scans were made during treatment. The clinical target volume (CTV) and the rectum were outlined in all scans. Lateral portal images were simulated from the CT data and difference images were calculated for all possible combinations of CT scans per patient; each scan was used both as reference and repeat scan but gas pockets in the reference scan were removed. Gas pockets in a repeat CT scan then show up as black areas in a difference image. Due to gravity, they normally appear in the ventral part of the rectum. The distances between the ventral edge of a gas pocket in a difference image and the projection of the delineated ventral rectum wall in the reference scan were calculated. These distances were correlated with the "true" rectum wall shifts (determined from direct comparison of the rectum delineations in reference and repeat scan) and with CTV movements determined by three-dimensional chamfer matching. Gas pockets occurred in 23% of cases. Nevertheless, about 50% of rectum wall shifts larger than 5 mm could be detected because they were associated with gas pockets with a lateral diameter > 2 cm. When gas pockets were visible in the repeat scan, rectum wall shifts could be accurately detected by the ventral gas pocket edge in the difference images (r= 0.97). The shift of the rectum wall as detected from gas pockets also correlated significantly with the anterior-posterior shift of the center of mass of the CTV (r=0.88). In conclusion, the simulations showed that lateral pelvic images contain more information than the bony structures that are normally used for setup verification. If large gas pockets appear in those images, a quantitative estimate of the position of prostate and rectum wall can be obtained by determination of the ventral edge of the gas pocket.

Humans↗
PubMed1999

Comparison of prostate cancer treatment in two institutions: a quality control study.

PURPOSE: To minimize differences in the treatment planning procedure between two institutions within the context of a radiotherapy prostate cancer trial. PATIENTS AND METHODS: Twenty-two patients with N0 M0 prostate cancer underwent a computed tomography (CT) scan for radiotherapy treatment planning. For all patients, the tumor and organs at risk were delineated, and a treatment plan was generated for a three-field technique giving a dose of 78 Gy to the target volume. Ten of the 22 cases were delineated and planned in the other institution as well. The delineated volumes and dose distributions were compared. RESULTS: All treatments fulfilled the trial criteria. The mean volume ratio of the gross tumor volumes (GTVs) in both institutions was 1.01, while the mean volume ratio of the planning target volumes (PTVs) was 0.88. The three-dimensional (3D) PTV difference was 3 mm at the prostate apex and 6-8 mm at the seminal vesicles. This PTV difference was mainly caused by a difference in the method of 3D expansion, and disappeared when applying an improved algorithm in one institution. The treated volume (dose > or =95% of isocenter dose) reflects the size of the PTV and the conformity of the treatment technique. This volume was on average 66 cm3 smaller in institution A than in institution B; the effect of the PTV difference was 31 cm3 and the difference in technique accounted for 36 cm3. The mean delineated rectal volume including filling was 112 cm3 and 125 cm3 for institution A and B, respectively. This difference had a significant impact on the relative dose volume histogram (DVH) of the rectum. CONCLUSION: Differences in GTV delineation were small and comparable to earlier quantified differences between observers in one institution. Different expansion methods for generation of the PTV significantly influenced the amount of irradiated tissue. Strict definitions of target and normal structures are mandatory for reliable trial results.

Humans↗
PubMed1999

Acute morbidity reduction using 3DCRT for prostate carcinoma: a randomized study.

PURPOSE: To study the effects on gastrointestinal and urological acute morbidity, a randomized toxicity study, comparing conventional and three-dimensional conformal radiotherapy (3DCRT) for prostate carcinoma was performed. To reveal possible volume effects, related to the observed toxicity, dose-volume histograms (DVHs) were used. METHODS AND MATERIALS: From June 1994 to March 1996, 266 patients with prostate carcinoma, stage T1-4N0M0 were enrolled in the study. All patients were treated to a dose of 66 Gy (ICRU), using the same planning procedure, treatment technique, linear accelerator, and portal imaging procedure. However, patients in the conventional treatment arm were treated with rectangular, open fields, whereas conformal radiotherapy was performed with conformally shaped fields using a multileaf collimator. All treatment plans were made with a 3D planning system. The planning target volume (PTV) was defined to be the gross target volume (GTV) + 15 mm. Acute toxicity was evaluated using the EORTC/RTOG morbidity scoring system. RESULTS: Patient and tumor characteristics were equally distributed between both study groups. The maximum toxicity was 57% grade 1 and 26% grade 2 gastrointestinal toxicity; 47% grade 1, 17% grade 2, and 2% grade > 2 urological toxicity. Comparing both study arms, a reduction in gastrointestinal toxicity was observed (32% and 19% grade 2 toxicity for conformal and conventional radiotherapy, respectively; p = 0.02). Further analysis revealed a marked reduction in medication for anal symptoms: this accounts for a large part of the statistical difference in gastrointestinal toxicity (18% vs. 14% [p = ns] grade 2 rectum/sigmoid toxicity and 16% vs. 8% [p < 0.0001] grade 2 anal toxicity for conventional and conformal radiotherapy, respectively). A strong correlation between exposure of the anus and anal toxicity was found, which explained the difference in anal toxicity between both study arms. No difference in urological toxicity between both treatment arms was found, despite a relatively large difference in bladder DVHs. CONCLUSIONS: The reduction in gastrointestinal morbidity was mainly accounted for by reduced toxicity for anal symptoms using 3DCRT. The study did not show a statistically significant reduction in acute rectum/sigmoid and bladder toxicity.

Colon, Sigmoid↗
PubMed1999

[Re-irradiation with hyperthermia in patients with recurrent breast cancer].

In the Daniel den Hoed Cancer Centre in Rotterdam, the Netherlands, patients with recurrent breast cancer within a previously irradiated area, are treated by application of hyperthermia in addition to reirradiation. In this development, the following issues are important: (a) the choice of an effective and tolerable reirradiation schedule; (b) the establishment of the limitations of the hyperthermia techniques available; (c) the finding that additional hyperthermia has to be applied to the total tissue volume at risk for tumour recurrence; (d) the assessment of the value of additional hyperthermia by a randomised study. With the reirradiation schedule of 8 x 4 Gy and the hyperthermia application technique at present available, local control is achieved in 76% of the patients for a median duration of 32 months. The probability of local control is related to tumour size. The treatment is tolerated well, with acceptable toxicity. In patients with recurrent breast cancer in a previously irradiated area, combined reirradiation and hyperthermia is very effective, well tolerated and little toxic.

Aged↗
PubMed1999

Internal organ motion in prostate cancer patients treated in prone and supine treatment position.

BACKGROUND AND PURPOSE: To compare supine and prone treatment positions for prostate cancer patients with respect to internal prostate motion and the required treatment planning margins. MATERIALS AND METHODS: Fifteen patients were treated in supine and fifteen in prone position. For each patient, a planning computed tomography (CT) scan was used for treatment planning. Three repeat CT scans were made in weeks 2, 4, and 6 of the radiotherapy treatment. Only for the planning CT scan, laxation was used to minimise the rectal content. For all patients, the clinical target volume (CTV) consisted of prostate and seminal vesicles. Variations in the position of the CTV relative to the bony anatomy in the four CT scans of each patient were assessed using 3D chamfer matching. The overall variations were separated into variations in the mean CTV position per patient (i.e. the systematic component) and the average 'day-to-day' variation (i.e. the random component). Required planning margins to account for the systematic and random variations in internal organ position and patient set-up were estimated retrospectively using coverage probability matrices. RESULTS: The observed overall variation in the internal CTV position was larger for the patients treated in supine position. For the supine and prone treatment positions, the random components of the variation along the anterior-posterior axis (i.e. towards the rectum) were 2.4 and 1.5 mm (I standard deviation (1 SD)), respectively; the random rotations around the left-right axis were 3.0 and 2.9 degrees (1 SD). The systematic components of these motions (1 SD) were larger: 2.6 and 3.3 mm, and 3.7 and 5.6 degrees, respectively. The set-up variations were similar for both treatment positions. Despite the smaller overall variations in CTV position for the patients in prone position, the required planning margin is equal for both groups (about 1 cm except for 0.5 cm in lateral direction) due to the larger impact of the systematic variations. However, significant time trends cause a systematic ventral-superior shift of the CTV in supine position only. CONCLUSIONS: For internal prostate movement, it is important to distinguish systematic from random variations. Compared to patients in supine position, patients in prone position had smaller random but somewhat larger systematic variations in the most important coordinates of the internal CTV position. The estimated planning margins to account for the geometrical uncertainties were therefore similar for the two treatment positions.

Algorithms↗
PubMed1998

Multiple two-dimensional versus three-dimensional PTV definition in treatment planning for conformal radiotherapy.

PURPOSE: To demonstrate the need for a fully three-dimensional (3D) computerized expansion of the gross tumour volume (GTV) or clinical target volume (CTV), as delineated by the radiation oncologist on CT slices, to obtain the proper planning target volume (PTV) for treatment planning according to the ICRU-50 recommendations. MATERIALS AND METHODS: For 10 prostate cancer patients two PTVs have been determined by expansion of the GTV with a 1.5 cm margin, i.e. a 3D PTV and a multiple 2D PTV. The former was obtained by automatically adding the margin while accounting in 3D for GTV contour differences in neighbouring slices. The latter was generated by automatically adding the 1.5 cm margin to the GTV in each CT slice separately; the resulting PTV is a computer simulation of the PTV that a radiation oncologist would obtain with (the still common) manual contouring in CT slices. For each patient the two PTVs were compared to assess the deviations of the multiple 2D PTV from the 3D PTV. For both PTVs conformal plans were designed using a three-field technique with fixed block margins. For each patient dose-volume histograms and tumour control probabilities (TCPs) of the (correct) 3D PTV were calculated, both for the plan designed for this PTV and for the treatment plan based on the (deviating) 2D PTV. RESULTS: Depending on the shape of the GTV, multiple 2D PTV generation could locally result in a 1 cm underestimation of the GTV-to-PTV margin. The deviations occurred predominantly in the cranio-caudal direction at locations where the GTV contour shape varies significantly from slice to slice. This could lead to serious underdosage and to a TCP decrease of up to 15%. CONCLUSIONS: A full 3D GTV-to-PTV expansion should be applied in conformal radiotherapy to avoid underdosage.

Humans↗
PubMed1998

In vivo dosimetry for prostate cancer patients using an electronic portal imaging device (EPID); demonstration of internal organ motion.

PURPOSE: To investigate the use of a commercially available video-based EPID for in vivo dosimetry during treatment of prostate cancer patients. METHODS: For 10 prostate cancer patients, the inter-fraction variation within measured portal dose images (PDIs) was assessed and measured PDIs were compared with corresponding predicted PDIs based on the planning CT scan of the patient. RESULTS: For the lateral fields, the average standard deviation in the measured on-axis portal doses during the course of a treatment was 0.9%; for the anterior fields this standard deviation was 2.2%. The difference between the average on-axis measured portal dose and the predicted portal dose was 0.3+/-2.1% (1 SD) for the lateral fields and 0.7+/-3.4% (1 SD) for the anterior fields. Off-axis differences between measured and predicted portal doses were regularly much larger (up to 15%) and were caused by frequently occurring gas pockets inside the rectum of the patients during treatment or during acquisition of the planning CT scan. The detected gas pockets did sometimes extend into the gross tumour volume (GTV) area as outlined in the planning CT scans, implying a shift of the anterior rectum wall and prostate in the anterior direction (internal organ motion). CONCLUSIONS: The developed procedures for measurement and prediction of PDIs allow accurate dosimetric quality control of the treatment of prostate cancer patients. Comparing measured PDIs with predicted PDIs can reveal internal organ motion.

Follow-Up Studies↗
PubMed1997

Muscle invasive bladder cancer treated by transurethral resection, followed by external beam radiation and interstitial iridium-192.

PURPOSE: To evaluate the results of transurethral resection (TUR), external beam radiotherapy (EBRT), and interstitial radiation (IRT) with iridium-192, using the afterloading technique in patients with muscle invasive bladder cancer. METHODS AND MATERIALS: From May 1989 until September 1995, 66 patients with primary, solitary muscle invasive bladder cancer were treated with TUR, EBRT, and IRT, aiming at bladder preservation. According to the protocol, in three patients low-dose EBRT was applied, whereas 63 patients received high-dose EBRT. Immediately prior to IRT, 42 patients underwent a lymphnode dissection, and in 16 cases a partial cystectomy was performed. For IRT, two to five catheters were used and IRT was started within 24 h after surgery. The majority of patients received 30 Gy of IRT, with a mean dose rate of .58 Gy/h. In three patients, additional EBRT was applied following IRT. Follow-up consisted of regular cystoscopies, mostly done during joint clinics of urologist and radiation oncologist, with urine cytology routinely performed. The median follow-up period was 26 months. The Kaplan-Meier method was used for the determination of survival rates. RESULTS: In seven patients, a bladder relapse developed. The probability of remaining bladder relapse free at 5 years was 88%. The bladder was preserved in 98% of the surviving patients. Metastases developed in 16 patients, and the probability of remaining metastasis free at 5 years was 66%. The cumulative 5-year overall and bladder and distant relapse free survival were 48% and 69%, respectively. Acute toxicity was not serious in the majority of cases; surgical correction of a persisting vesicocutaneous fistula was necessary in two patients, whereas a wound toilet had to be performed in another patient. Serious late toxicity (bladder, RTOG Grade 3) was experienced by only one patient. CONCLUSIONS: Interstitial radiation preceded by TUR and EBRT, in a selected group of patients with muscle invasive bladder cancer, yields an excellent bladder tumor control rate with a high probability of bladder preservation. Survival was mainly dependent on the development of distant metastases. Serious acute and late toxicity was rare.

Adenocarcinoma↗
PubMed1997

Field margin reduction using intensity-modulated x-ray beams formed with a multileaf collimator.

PURPOSE: In axial, coplanar treatments with multiple fields, the superior and inferior ends of a planning target volume (PTV) are at risk to get underdosed due to the overlapping penumbras of all treatment fields. We have investigated a technique using intensity modulated x-ray beams that allows the use of small margins for definition of the superior and inferior field borders while still reaching a minimum PTV-dose of 95% of the isocenter dose. METHODS AND MATERIALS: The applied intensity modulated beams, generated with a multileaf collimator, include narrow (1.1-1.6 cm) boost fields to increase the dose in the superior and inferior ends of the PTV. The benefits of this technique have been assessed using 3D treatment plans for 10 prostate cancer patients. Treatment planning was performed with the Cadplan 3D planning system (Varian-Dosetek). Dose calculations for the narrow boost fields have been compared with measurements. The application of the boost fields has been tested on the MM50 Racetrack Microtron (Scanditronix Medical AB), which allows fully computer-controlled setup of all involved treatment fields. RESULTS: Compared to our standard technique, the superior-inferior field length can be reduced by 1.6 cm, generally yielding smaller volumes of rectum and bladder in the high dose region. For the narrow boost fields, calculated relative dose distributions agree within 2% or 0.2 cm with measured dose distributions. For accurate monitor unit calculations, the phantom scatter table used in the Cadplan system had to be modified using measured data for square fields smaller than 4 x 4 cm2. The extra time needed at the MM50 for the setup and delivery of the boost fields is usually about 1 min. CONCLUSION: The proposed use of intensity modulated beams yields improved conformal dose distributions for treatment of prostate cancer patients with a superior-inferior field size reduction of 1.6 cm. Treatments of other tumor sites can also benefit from the application of the boost fields.

Humans↗
PubMed1994

Optimizing brachytherapy for locally advanced cervical cancer.

PURPOSE: No adequate high dose rate brachytherapy technique exists to cover all known tumor volume by using one type of applicator in patients presenting with a cervix carcinoma extending to the vaginal wall and the parametria. METHODS AND MATERIALS: We adapted the existing high dose rate applicator, existing of two ovoids and one intrauterine tube, to achieve adequate irradiation of the uterus, the parametria, and the vaginal wall in these patients. Using the optimization program of the Nucletron Planning System, isodose curves were obtained to apply a specified dose of 8.5 Gy at point A and at 5 mm depth of the vaginal wall by using a single applicator for both fractions. RESULTS: Fractionated high dose rate brachytherapy can be given with both higher dosimetric accuracy and more adequate irradiation of the vaginal and the parametrial tumor component after adapting the existing high dose rate applicator for brachytherapy in cervical cancer.

Brachytherapy↗
PubMed1994

The pedicled omentoplasty, a simple and effective surgical technique to acquire a safe pelvic radiation field; theoretical and practical aspects.

A substantial number of patients need radiotherapy after surgery for pelvic malignancy. Approximately 15% of them will experience radiation enteritis. After omentoplasty, reduction of irradiated bowel volume may be obtained. We evaluated the pedicled omentoplasty during gynaecologic surgery as a technique to improve safe irradiation of the pelvic region.

Case-Control Studies↗
PubMed1993

Axillary nodal metastases from an occult primary consistent with breast carcinoma.

The records of 15 women presenting with axillary nodal metastases from an occult primary consistent with breast carcinoma were reviewed. Nine patients underwent complete axillary clearance and in six the clinical mass only was excised. Radiotherapy to the axilla was given to eight patients. One woman underwent mastectomy at the time of axillary surgery but no tumour was found in the excised breast; in the remaining 14 patients the breast was left untreated. One premenopausal woman received adjuvant systemic chemotherapy and one postmenopausal patient was given tamoxifen. Three patients died from recurrent disease at 16, 50 and 56 months after treatment of the axillary mass; one is alive at 42 months with systemic recurrence. In two of these patients the tumour in the breast became apparent before other metastases. Eleven patients survived for a median of 92 (range 18-144) months without evidence of disease. The prognosis of this patient group is better than that generally reported for stage II breast carcinoma.

Adenocarcinoma↗
PubMed1993

Recurrent endometrial adenocarcinoma after surgery alone: prognostic factors and treatment.

Twenty-six patients with a local and/or regional relapse of a previously surgically treated adenocarcinoma of the endometrium were referred to the Dr. Daniel den Hoed Cancer Center (DDHCC) in Rotterdam, The Netherlands between 1965 and 1985 for external radiotherapy (ERT) and/or brachytherapy (BT). The 5-year overall survival was 44%. Tumour volume seemed to be an important prognostic factor in locoregional control; 1 out of 17 patients with tumour sizes smaller than or equal to 4 cm relapsed locoregionally, while in 3 out of 9 patients with tumour sizes of more than 4 cm a locoregional recurrence developed. Another important finding is the impact of RT on treatment outcome: none of the 16 patients treated with a combination of ERT and BT failed locoregionally, while 4 out of 10 patients treated with either ERT or BT relapsed.

Adenocarcinoma↗