Daniel Taussky

Quality of life in patients cured from a carcinoma of the head and neck by radiotherapy : The importance of the target volume

PURPOSEnTo assess the health-related quality of life (QOL) of long-term survivors of carcinomas of different subsites of the head and neck following curative radiotherapy (RT).nnnPATIENTS AND METHODSnPatients continuously free from recurrence or second primary tumors treated 1988-1994 were contacted 5.1 to 5.9 years after RT and asked to fill in the EORTC QLQ-C30 core questionnaire and the H&N cancer module. RT had been restricted to the glottis (group A; carcinomas of the vocal cord T1-2 N0), or had included bilateral neck nodes and the primary tumor outside the nasopharynx (group B; AJC Stage II to IV) or within the nasopharynx, respectively (group C; Stage II to IV). Response rate was 97% (group A; n = 41), 69% (group B; n = 26) and 71% (group C; n = 12), respectively. The groups were different with respect to age (older in group A), alcohol consumption (absent in group C) and proportion of females (more in group C).nnnRESULTSnPatients with nasopharyngeal cancer reported the highest morbidity on the H&N module (dry mouth, sticky saliva, trismus, problems with teeth, trouble eating). However, these symptoms did not have a high impact on global QOL or function scores on the QLQ-C30 core questionnaire. Patients in group B reported a lower global QOL but less severe symptoms on the module.nnnCONCLUSIONnThe high morbidity of patients treated for a nasopharyngeal cancer may be explained by the location of the target volume which included the bilateral temporo-mandibular joints and the salivary glands. These patients require appropriate care during follow-up and will probably profit most from new RT techniques with sparing of normal tissues.

Salvage surgery after radical accelerated radiotherapy with concomitant boost technique for head and neck carcinomas.

Definitive radiotherapy (RT) for head and neck cancer is increasingly used to preserve organ function, whereas surgery is reserved for treatment failure. However, data are sparse regarding the feasibility of salvage surgery, particularly for unselected patients after accelerated RT.

Hyperfractionated radiotherapy and simultaneous cisplatin for stage-III and-IV carcinomas of the head and neck

PurposeTo assess the survival rate, the probability of local control, the patterns of relapse and late sequelae including self-reported quality of life in patients treated with hyperfractionated radiotherapy (RT) and simultaneous CDDP chemotherapy for stage-III to stage-IV carcinomas of the head and neck.MethodsFrom 1988 to 1994, 64 patients (median age 55.5 years) with carcinomas of different subsites, excluding the nasopharynx, were treated in a pilot study with 1.2 Gy bid (6 h interval; total dose 74.4 Gy) and simultaneous CDDP (20 mg/m2 daily, 5 days in week 1 and 5) and followed at regular intervals. Overall survival and local control, as well as the rates of late toxicity, were estimated using the actuarial method. Median follow-up was 3.3 years for all and 5.2 years for surviving patients. To assess the quality of life, the EORTC QLQ-C 30 questionnaire and the H&N35 module questionnaire were sent to the patients surviving with no evidence of disease or second primary tumors; they were answered by 15/23 (67%).ResultsOverall survival was 37% at 5 years, whereas disease-specific survival was 59%. Twenty-three patients died from uncontrolled head and neck cancer. Second primary tumors were observed in 13 patients, most frequently in the lung. Local control without salvage surgery was 74% at 5 years for all subsites and stages, and loco-regional disease-free survival was 72%. Eleven patients developed distant metastases, which was the only site of failure in 6 cases. Salvage surgery was successful in 2 cases. The actuarial estimates of ≥ grade-3 late toxicity was 4% for the mandibular bone and 23% for dysphagia, and 50% of the patients experienced a permanent xerostomy. Self-reported global quality of life in surviving patients was good (mean 68 points on a scale 0 to 100); consequences of impaired salivary function had most impact on nutritional and social aspects.ConclusionsHyperfractionated RT with concomitant CDDP is well tolerated and highly efficient in controlling moderately advanced to advanced cancers of the head and neck. Second primary tumors are the main cause of death after 3 years and were observed outside of the irradiated area, most frequently in the lung. Even after RT of large volumes to a high dose, salvage surgery can be successfully performed in individual cases. Self-reported quality of life of surviving patients is good, despite xerostomy-associated nutritional difficulties.ZusammenfassungZielAnalyse der Überlebensrate, des krankheitsspezifischen Überlebens, des Rezidivmusters, der Spättoxizität sowie der subjektiven Lebensqualität nach hyperfraktionierter Radiotherapie (RT) und gleichzeitiger Cisplatin-Chemotherapie (CDDP) bei Patienten mit mindestens zwei Jahren Beobachtungszeit im Rahmen einer prospektiven Phase-II-Studie.Patienten und MethodeIm Rahmen einer Pilotstudie (1988 bis 1994) wurden 64 Patienten (medianes Alter 55,5 Jahre) mit Stadium III oder IV kombiniert behandelt: RT 1,2 Gy zweimal täglich bis 74,4 Gy, CDDP 20 mg/m2 täglich an den Tagen 1 bis 5 der ersten und fünften Woche. Die Überlebenskurven sowie die Toxizität wurden aktuariell berechnet. Die mediane Beobachtungszeit war 3,3 Jahre für alle respektive 5,2 Jahre für die überlebenden Patienten. Zur Einschätzung der Lebensqualität wurden 23 tumorfrei überlebende Patienten angefragt, den EORTC-QLQ-C30-Fragebogen sowie das ergänzende Modul für Kopf-Hals-Tumoren H&N35 auszufüllen.ErgebnisseDas Gesamtüberleben betrug nach fünf Jahren 37%, während das krankheitsspezifische Überleben mit 59% deutlich höher lag. 23 Patienten sind am Tumor verstorben. Zweittumoren, hauptsächlich Lungenkarzinome (n=8), wurden bei 13 Patienten registriert und waren die hauptsächliche Todesursache nach über drei Jahren. Die lokale Tumorkontrolle ohne zusätzliche Chirurgie betrug 74% nach fünf Jahren und war für alle Lokalisationen und Stadien gleich; die lokoregionäre Tumorkontrollrate lag bei 64%. Fernmetastasen ohne ein lokoregionäres Therapieversagen wurden bei sechs Patienten gesehen. Eine „Rettungschirurgie” wurde in zwei Fällen erfolgreich durchgeführt. Die aktuarielle Spätkomplikationsrate ≥ Grad 3 betrug 4% für den Kieferknochen und 23% für Dysphagie; 50% der Patienten hatten eine bleibende komplette Xerostomie. Die globale Lebensqualität war gut (im Mittel 68 Punkte auf einer Skala von 0 bis 100). Folgen der gestörten Speichelsekretion hatten die größte Auswirkung auf die funktionelle Behinderung der Ernährung sowie der sozialen Kontakte.SchlußfolgerungenDie hyperfraktionierte RT mit gleichzeitiger CDDP-Gabe wird hinsichtlich Spättoxizität gut toleriert und ist effizient zur Behandlung fortgeschrittener Kopf-Hals-Tumoren. Im Gegensatz zu chirurgischen Serien treten Zweitkarzinome praktisch nur außerhalb des ursprünglichen Tumorbereichs auf. Eine „Rettungschirurgie” nach initialem Therapieversagen ist auch nach RT mit 74,4 Gy in Einzelfällen erfolgreich. Die selbstrapportierte Lebensqualität bei den Langzeitüberlebenden ist generell gut trotz gewisser, vorwiegend xerostomiebedingter Einschränkungen.

Influence of rectal volume changes during radiotherapy for prostate cancer: A predictive model for mild-to-moderate late rectal toxicity

PURPOSEnTo assess the rectal volume changes during radiotherapy for prostate cancer, to estimate an average rectal dose distribution profile during treatment, and to correlate these parameters with mild-to-moderate late rectal toxicity.nnnMATERIALS AND METHODSnNine patients with localized prostate cancer underwent virtual CT simulation using a six-field conformal 18-MV photon technique. During treatment, patients underwent weekly pelvic CT scans under simulation conditions. Dosimetries were run with each CT data set using the same beam parameters as in the initial treatment plan. The influence of weekly rectal volume changes on the dose-volume histogram (DVH) profiles was studied. A polynomial function correlating the initial rectal volume with the mean percentage of change in the rectal volume during treatment was used to define a correction factor for rectal DVHs. The model was validated using data from 100 patients treated with 74 Gy according to the same technique. Areas under the curve of the initial rectal DVHs were correlated with toxicity (Radiation Therapy Oncology Group Grade 0 vs. 1-2, Students t test), with or without the use of the above correction factor.nnnRESULTSnA trend for enlargement of the rectal volume during treatment was observed for most patients in the study with small rectal volumes (<75 cm(3)) at simulation, resulting in an increase in the integral rectal dose by a factor ranging from 1.3 to 2.1. Corrected, but not uncorrected, rectal DVH profiles were strongly predictive of Grade 0 vs. 1-2 late rectal morbidity.nnnCONCLUSIONSnCorrecting the area under the curve of the rectal DVH at simulation by a factor that takes into account the projected volume changes during treatment correlates significantly with the probability of mild-to-moderate late rectal toxicity (Grade 1-2). This reliable predictor for mild-to-moderate late rectal morbidity may also be a practical tool for treatment planning.

Analysis of seed loss and pulmonary seed migration in patients treated with virtual needle guidance and robotic seed delivery.

Purpose and BackgroundTo determine whether automated seed delivery system and real-time intraoperative (IO) virtual needle guidance reduce seed loss and pulmonary seed migration. Patients and MethodsWe analyzed 279 patients with low and intermediate risk prostate cancer treated in our institution with radioactive iodine (I-125) permanent seed implants. Loose seeds were exclusively used. To account for lost seeds, pelvic fluoroscopic imaging from 3 different angles was done 30 days after the implant. Posteroanterior and lateral chest x-rays were done when seed loss was confirmed. Patients were compared using the &khgr;2 test and Fisher exact test. ResultsAt least 1 seed was lost in 31.5% of patients with a migration rate of 1.02%; 9.3% of patients had at least 1 seed in the lung with a migration rate of 0.22%. The population was divided into 3 groups according to the order in which they were treated. Seed loss (P=0.02) and pulmonary seed embolization (P=0.008) were significantly lower in the second hundred than in the first hundred patients. No difference was noted between groups 1 and 3 (patient, 201–279). Peri- or extracapsular seed placement was not correlated to seed loss (P=0.780 and P=0.092, respectively). No serious complications from seed migration were reported. Seed loss did not influence dosimetry parameters (V100, V150, and D90). ConclusionOur pulmonary seed migration and total seed loss rates are comparable to the ones reported in the literature. Virtual needle guidance and automated seed delivery system are in our hand as accurate as the manual technique.

Poor Predictive Value of Intraoperative Real-Time Dosimetry for Prostate Seed Brachytherapy

PURPOSEnTo identify dosimetric parameters predictive of a good prostate seed I(125) quality implant. We analyzed preimplant and postimplant realtime dosimetry in patients treated with intraoperative (IO) inverse planning.nnnMETHODS AND MATERIALSnWe analyzed 127 consecutively treated patients with primarily low-risk prostate carcinoma who underwent prostate permanent seed I(125) brachytherapy using an IO planning approach. The implant was done using the three-dimensional transrectal ultrasound (PRE-TRUS)-guided IO interactive inverse preplanning system. The TRUS was repeated in the operating room after the implant procedure was complete (POST-TRUS). The prostate was recontoured and postimplant dosimetry was calculated. Each patient underwent computed tomography scan on Day 28 (CT-D28) to evaluate implant quality. Area under the receiver operating characteristic curves (AUROC) was evaluated for models predictive of a V100 of > or =90% and a D90 of > or =140 Gy on the basis of CT-D28 values.nnnRESULTSnOn CT-D28, 72.4% of patients had a V100 of > or =90% and 74.8% had a D90 of > or =140 Gy. AUROC for a V100 of > or =90% was 0.665 (p = 0.004) on PRE-TRUS and 0.619 (p = 0.039) on POST-TRUS. AUROC for D90 of > or =140 Gy was 0.602 (p = 0.086) on PRE-TRUS and 0.614 (p = 0.054) on POST-TRUS. Using PRE-TRUS V100 cutoff of >97% gives sensitivity of 88% and a false-positive rate of 63%. A POST-TRUS D90 cutoff of >170 Gy resulted in a sensitivity of 62% and a false-positive rate of 34%.nnnCONCLUSIONSnBecause of unacceptably high false-positive rates, IO preimplant and postimplant TRUS-based dosimetry are not accurate tools to predict for postimplant computed tomography-based dosimetry.

Single-fraction high-dose-rate brachytherapy using real-time transrectal ultrasound based planning in combination with external beam radiotherapy for prostate cancer: dosimetrics and early clinical results

Purpose To validate the feasibility of a single-fraction high-dose-rate brachytherapy (HDRBT) boost for prostate cancer using real-time transrectal ultrasound (TRUS) based planning. Material and methods From August 2012 to September 2015, 126 patients underwent a single-fraction HDRBT boost of 15 Gy using real-time TRUS based planning. External beam radiation therapy (EBRT) (37.5 Gy/15 fractions, 44 Gy/22 fractions, or 45 Gy/25 fractions) was performed before (31%) or after (69%) HDRBT boost. Genito-urinary (GU) and gastro-intestinal (GI) toxicity were assessed 4 and 12 months after the end of combined treatment using the international prostate symptom score scale (IPSS) and the common terminology criteria for adverse events (CTCAE) v3.0. Results All dose-planning objectives were achieved in 90% of patients. Prostate D90 ≥ 105% and ≤ 115% was achieved in 99% of patients, prostate V150 ≤ 40% in 99%, prostate V200 < 11% in 96%, urethra D10 < 120% for 99%, urethra V125 = 0% in 100%, and rectal V75 < 1 cc in 93% of patients. Median IPSS score was 4 at baseline and did not change at 4 and 12 months after combined treatment. No patients developed ≥ grade 2 GI toxicity. With a median follow-up of 10 months, only two patients experienced biochemical failure. Among patients who didnt receive ADT, cumulative percentage of patients with PSA ≤ 1 ng/ml at 4 and 18 months was respectively 23% and 66%. Conclusions Single-fraction HDRBT boost of 15 Gy using real-time TRUS based planning achieves consistently high dosimetry quality. In combination with EBRT, toxicity outcomes appear promising. A longer follow-up is needed to assess long-term outcome and toxicities.

Refining prostate seed brachytherapy: Comparing high-, intermediate-, and low-activity seeds for I-125 permanent seed prostate brachytherapy

PURPOSEnTo analyze the difference in prostate coverage and dose to the rectum in men with prostate carcinoma treated with permanent seed brachytherapy with different seed activities.nnnMETHODSnForty-nine patients treated with iodine-125 permanent seed prostate brachytherapy with low-activity seeds of 0.30-0.37xa0mCi were identified. For each of these patients, 2 patients with similar prostate volume (±2 cc) were paired: one treated with intermediate seed activity (0.44-0.46xa0mCi) and one with high seed activity (0.60-0.66xa0mCi). The doses to prostate and rectum were compared using CT on Dayxa030.nnnRESULTSnA total of 147 patients divided into the three seed activity groups were analyzed. Mean prostate volume was 35.7 cc (standard deviation [SD], 11.70). Compared with low-activity seeds, implants with high-activity seeds consisted of an average of 22 seeds and 4.7 needles less. The dose to the prostate (prostate volume receiving 100% of the prescribed dose [V100], prostate volume receiving 150% of the prescribed dose, and minimal dose covering 90% of the prostate volume expressed in Gy) was not higher on Day 30 (pxa0= 0.58-0.97). The mean volume (in cubic centimeters) of rectal wall receiving 100% of the prescribed dose (V100) increased with activity: low activity, 0.34 cc (SD, 0.49), intermediate activity, 0.47 cc (SD, 0.48), and high activity, 0.72 cc (SD, 0.79) (pxa0= 0.009). There was a trend (pxa0= 0.073) toward a higher frequency of clinically unfavorable rectal dosimetry (V100xa0>xa01.3 cc) in patients with high-activity seeds (16.7%) compared with low-activity (6.3%) or intermediate-activity (4.2%) seeds.nnnCONCLUSIONnHigh-activity seeds do not result in a higher dose to the prostate but in a higher dose to the rectum.

Is intraoperative real-time dosimetry in prostate seed brachytherapy predictive of biochemical outcome?

Purpose To analyze intraoperative (IO) dosimetry using transrectal ultrasound (TRUS), performed before and after prostate low-dose-rate brachytherapy (LDR-BT), and compare it to dosimetry performed 30 days following the LDR-BT implant (Day 30). Material and methods A total of 236 patients underwent prostate LDR-BT using 125I that was performed with a three-dimensional TRUS-guided interactive inverse preplanning system (preimplant dosimetry). After the implant procedure, the TRUS was repeated in the operating room, and the dosimetry was recalculated (postimplant dosimetry) and compared to dosimetry on Day 30 computed tomography (CT) scans. Area under curve (AUC) statistics was used for models predictive of dosimetric parameters at Day 30. Results The median follow-up for patients without BF was 96 months, the 5-year and 8-year biochemical recurrence (BR)-free rate was 96% and 90%, respectively. The postimplant median D90 was 3.8 Gy lower (interquartile range [IQR], 12.4-0.9), and the V100 only 1% less (IQR, 2.9-0.2%) than the preimplant dosimetry. When comparing the postimplant and the Day 30 dosimetries, the postimplant median D90 was 9.6 Gy higher (IQR [–] 9.5-30.3 Gy), and the V100 was 3.2% greater (0.2-8.9%) than Day 30 postimplant dosimetry. The variables that best predicted the D90 of Day 30 was the postimplant D90 (AUC = 0.62, p = 0.038). None of the analyzed values for IO or Day 30 dosimetry showed any predictive value for BR. Conclusions Although improving the IO preimplant and postimplant dosimetry improved dosimetry on Day 30, the BR-free rate was not dependent on any dosimetric parameter. Unpredictable factors such as intraprostatic seed migration and IO factors, prevented the accurate prediction of Day 30 dosimetry.

Fusion of Intraoperative Transrectal Ultrasound Images with Post-implant Computed Tomography and Magnetic Resonance Imaging

Purpose To compare the impact of the fusion of intraoperative transrectal ultrasound (TRUS) images with day 30 computed tomography (CT) and magnetic resonance imaging (MRI) on prostate volume and dosimetry. Methods and materials Seventy-five consecutive patients with CT and MRI obtained on day 30 with a Fast Spin Echo T2-weighted magnetic resonance (MR) sequence were analyzed. A rigid manual registration was performed between the intraoperative TRUS and day-30 CT based on the prostate volume. A second manual rigid registration was performed between the intraoperative TRUS and the day-30 MRI. The prostate contours were manually modified on CT and MRI. The difference in prostate volume and dosimetry between CT and MRI were compared. Results Prostate volume was on average 8% (standard deviation (SD) ± 16%) larger on intraoperative TRUS than on CT and 6% (18%) larger than on MRI. In 48% of the cases, the difference in volume on CT was > 10% compared to MRI. The difference in prostate volume between CT and MRI was inversely correlated to the difference in D90 (minimum dose that covers 90% of the prostate volume) between CT and MRI (r = -0.58, P < .001). A D90 < 90% was found in 5% (n = 4) on MRI and in 10% (n = 7) on CT (Fisher exact test one-sided P = .59), but in no patient was the D90 < 90% on both MRI and CT. Conclusions When fusing TRUS images with CT and MRI, the differences in prostate volume between those modalities remain clinically important in nearly half of the patients, and this has a direct influence on how implant quality is evaluated.