Kauko Saarilahti

Patterns of relapse following surgery and postoperative intensity modulated radiotherapy for oral and oropharyngeal cancer

Abstract Background. To investigate the patterns of relapse following intensity modulated radiotherapy (IMRT) given after radical surgery for oral and oropharyngeal squamous cell cancer. Patients and methods. One hundred and two patients with oral or oropharyngeal cancer were treated with radical surgery followed by IMRT up to a mean total dose of 60 Gy between years 2001 and 2007. Thirty-nine of the patients (%) also received concomitant weekly cisplatin. Forty of the patients had oral and 62 had oropharyngeal cancer. Data on the tumour, patient and treatment factors were collected. Following therapy the patients were followed by clinical examination, endoscopy and MRI/CT at 2- to 3-months interval up to 2 years and thereafter at 6-month intervals. Results. The mean follow-up time of the patients was 55 months (range, 26–106 months). The rate for local tumour control for the whole cohort was 92.2%: 87.5% for oral cancer patients and 96.7% for oropharyngeal cancer patients. The 5-year disease specific survival was 90.2% and 5-year overall survival 84.3%. During the follow-up eight locoregional recurrences were observed, three at the primary tumour site and one at regional nodal site and four at both sites. The mean time to primary tumour recurrence was seven months (range, 2–10 months) and to nodal recurrence seven months (range, 2–12 months). Distant metastasis occurred in six (6%) patients. The factors associated with poor prognosis were the primary tumour size and tumour site with oral cancers having worse outcome. The treatment was well tolerated with no unexpected toxicities. The most frequent late toxicity was dysphagia necessitating permanent PEG in five patients. This was correlated with the advanced primary tumour size and resulting in wide tumour excision and reconstruction. Conclusions. Surgery combined with postoperative radiotherapy given as IMRT results in low level of tumour recurrence.

Pattern of recurrent disease in major salivary gland adenocystic carcinoma

This study aims to evaluate the long-term outcome of major salivary gland adenocystic carcinoma (ACC). This is a retrospective review of 54 cases of ACC during a 35-year period from 1974 to 2009 at the Helsinki University Central Hospital, Helsinki, Finland. Medical records and histological samples were reviewed. All patients had a minimum follow-up time of 5xa0years or until death. Most of the tumours occurred in the parotid gland (nu2009=u200930, 56xa0%) followed by submandibular gland (nu2009=u200922, 41xa0%) and sublingual gland (nu2009=u20092, 4xa0%). Fifty-two patients (96xa0%) were treated with curative intent. All of these patients except one were primarily treated with surgery, and 29 patients (54xa0%) also received postoperative radiotherapy for their primary tumour. Two patients (4xa0%) received palliative radiotherapy. For those treated with curative intent, 32 patients (62xa0%) had disease recurrence. Twenty-four patients (75xa0%) had their first disease recurrence within 5xa0years and eight patients (25xa0%) later than 5xa0years. The difference in the length of recurrence-free time interval (<5 vs. >5xa0years) had a significant impact on 5-year overall survival (OS) and disease-specific survival (DSS). The OS, DSS and disease-free survival (DFS) across stages I–IV varied between 46–100, 50–100 and 46–100xa0%, respectively. Age over 45xa0years, T stage, and presence of neck metastases had a significant negative prognostic effect. More than half of the patients had recurrent disease. An extended follow-up for these patients seems feasible as most of the distant metastases were detected within a 10-year period.

Radiotherapy in desmoid tumors

BackgroundDesmoid tumors (aggressive fibromatosis) are rare soft tissue tumors which frequently recur after surgery. Desmoid tumors arise from musculoaponeurotic tissue in the extremities, head and neck, abdominal wall, or intra-abdominally. Our aim was to examine the outcome of radiotherapy of desmoid tumors in axa0single institution series.Patients and methodsWe evaluated 41xa0patients with desmoid tumors treated with 49xa0radiotherapies between 1987 and 2012. Radiologic images for response evaluation were reassessed and responses to treatment registered according to RECIST criteria 1.1. For patients with local failures radiation dose distribution was determined in each local failure volume using image co-registration. Recurrences were classified as in-target, marginal, or out-of-target. Prognostic factors for radiotherapy treatment failure were evaluated.ResultsRadiotherapy doses varied from 20–63u2009Gy (median 50u2009Gy) with axa0median fraction size of 2u2009Gy. The objective response rate to definitive radiotherapy was 55% (12/22xa0patients). Median time to response was 14xa0months. Axa0statistically significant dose-response relation for definitive and postoperative radiotherapy was observed both in univariate (p-value 0.002) and in multivariate analysis (p-value 0.02) adjusted for potential confounding factors. Surgery before radiotherapy or surgical margin had no significant effect on time to progression. Nine of 11 (82%) local failures were classified as marginal and two of 11 (18%) in-target. None of the recurrences occurred totally out-of-target.ConclusionsRadiotherapy is axa0valuable option for treating desmoid tumors. Radiotherapy dose appears to be significantly associated to local control.ZusammenfassungHintergrundDesmoide (aggressive Fibromatosen) sind seltene Weichteiltumore der muskulären Membranen von Kopf, Hals, Extremitäten und Bauchwand. Ziel war es, die Wirksamkeit der Strahlentherapie bei aggressiver Fibromatose an einer einzelnen Klinik zu untersuchen.Patienten und MethodeAusgewertet wurden 41xa0Patienten mit aggressiver Fibromatose, die zwischen 1987 und 2012 mit 49xa0Strahlentherapien behandelt wurden. Das Ansprechen wurde anhand der radiologischen Aufnahmen neu beurteilt und der Behandlungserfolg gemäß RECIST-1.1-Kriterien registriert. Für Patienten mit Lokalrezidiv wurde die Dosisverteilung der Radiotherapie durch Fusion von diagnostischen CT- und MRT-Bildern mit den Planungs-CT-Aufnahmen für jedes Lokalrezidiv bestimmt. Die Rezidive wurden je nach Lage eingeteilt in: innerhalb, am Rande und außerhalb des ehemaligen Bestrahlungsvolumens gelegen. Prognostische Faktoren für ein Therapieversagen wurden ausgewertet.ErgebnisseDie Gesamtdosen der Strahlentherapie lagen zwischen 20 und 63u2009Gy (Median 50u2009Gy) mit einer medianen Fraktionierung von 2u2009Gy. Die objektive Ansprechrate war 55u2009% (12/22xa0Patienten). Die mediane Zeit bis zum Therapieerfolg betrug 14xa0Monate. Eine statistisch signifikante Dosis-Wirkungs-Beziehung für die definitive und die postoperative Strahlentherapie wurde sowohl in der univariaten (p-Wert 0,002) als auch in der für potentielle Störfaktoren korrigierenden multivariaten Analyse (p-Wert 0,02) beobachtet. Neun von 11 (82u2009%) Lokalrezidiven wurden als Feldrandrezidive und zwei von 11 (18u2009%) als innerhalb des Bestrahlungsfelds liegende Rezidive bewertet. Kein Lokalrezidiv trat komplett außerhalb des Bestrahlungsfelds auf.SchlussfolgerungDie Strahlentherapie ist eine wertvolle Therapiewahl zur Behandlung aggressiver Fibromatosen. Die Strahlentherapiedosis hat einen signifikanten Einfluss auf die lokale Kontrolle.

Boron Neutron Capture Therapy in the Treatment of Recurrent Laryngeal Cancer.

PURPOSEnTo investigate the safety and efficacy of boron neutron capture therapy (BNCT) as a larynx-preserving treatment option for patients with recurrent laryngeal cancer.nnnMETHODS AND MATERIALSnSix patients with locally recurrent squamous cell laryngeal carcinoma and 3 patients with persistent laryngeal cancer after prior treatment were treated with BNCT at the FiR1 facility (Espoo, Finland) in 2006 to 2012. The patients had received prior radiation therapy with or without concomitant chemotherapy to a cumulative median dose of 66 Gy. The median tumor diameter was 2.9 cm (range, 1.4-10.9 cm) before BNCT. Boron neutron capture therapy was offered on a compassionate basis to patients who either refused laryngectomy (n=7) or had an inoperable tumor (n=2). Boronophenylalanine-fructose (400 mg/kg) was used as the boron carrier and was infused over 2 hours intravenously before neutron irradiation.nnnRESULTSnSix patients received BNCT once and 3 twice. The estimated average gross tumor volume dose ranged from 22 to 38 Gy (W) (mean; 29 Gy [W]). Six of the 8 evaluable patients responded to BNCT; 2 achieved complete and 4 partial response. One patient died early and was not evaluable for response. Most common side effects were stomatitis, fatigue, and oral pain. No life-threatening or grade 4 toxicity was observed. The median time to progression within the target volume was 6.6 months, and the median overall survival time 13.3 months after BNCT. One patient with complete response is alive and disease-free with a functioning larynx 60 months after BNCT.nnnCONCLUSIONSnBoron neutron capture therapy given after prior external beam radiation therapy is well tolerated. Most patients responded to BNCT, but long-term survival with larynx preservation was infrequent owing to cancer progression. Selected patients with recurrent laryngeal cancer may benefit from BNCT.

Trends in the 15D health-related quality of life over the first year following diagnosis of head and neck cancer.

Management of head and neck cancer influences both physical and mental wellbeing. Measuring the health-related quality of life (HRQoL) is important, as various treatment modalities are associated with significant morbidity and mortality. In this prospective cohort study, we tested the feasibility of the generic 15D HRQoL instrument in 214 head and neck cancer patients managed with surgery, definitive (chemo)radiotherapy, or with combined modality treatment. HRQoL was assessed at baseline and three times after treatment onset during 1xa0year, and compared with that of general population standardized for age and sex. At baseline, the patients’ mean 15D score was significantly worse compared with general population. Overall HRQoL was at lowest at 3xa0months after treatment onset, it gradually improved towards 12xa0months but never reached baseline levels. The dimensions “vitality”, “distress”, “depression” and “sexual activity” showed marked deterioration at 3xa0months after the treatment onset, but improved gradually during 12xa0months. The 15D instrument seems useful for evaluation of HRQoL of head and neck cancer patients. Dimensions reflecting mental wellbeing improved gradually after 3xa0months, but they seldom reached baseline levels. The support for patients at the time of diagnosis, during treatment, and recovery is emphasized.

Biweekly escalated, accelerated hyperfractionated radiotherapy with concomitant single-dose mitomycin C results in a high rate of local control in advanced laryngeal and hypopharyngeal cancer.

Abstract: The purpose of this study is to evaluate the efficacy of a dose-escalated, accelerated, and hyperfractionated radiotherapy schedule with a concomitant single dose of mitomycin C in the treatment of patients with advanced laryngeal or hypopharyngeal cancer. Twenty-one previously untreated patients with advanced squamous cell carcinoma (stage III, n = 6; stage IV, n = 15) were treated with a biweekly dose-escalated, accelerated, and hyperfractionated schedule up to a total dose of 74.4 Gy in 54 fractions over 5 weeks. A single dose of intravenous mitomycin C 10 mg/m2 was given on day 30. The median follow-up after treatment of surviving patients is 48 months (range, 28 to 61 months). All patients showed complete tumor control at the primary site when evaluated 2 months after chemoirradiation by laryngomicroscopy or hypopharyngoscopy and radiologic imaging (CT, MRI). Two laryngectomies were carried out after given therapy: 1 for residual cancer and 1 for suspected residual cancer. After a median follow-up of 43 months (range, 28 to 61 months), a local control rate of 70% and disease-free survival (DFS) rate of 60% were achieved in the laryngeal cancer patients; in patients with hypopharyngeal cancer, the corresponding figures were 64% (82% after salvage surgery) and 36%. The results are promising and warrant comparison with other chemoradiotherapy regimens.

Converting from CT- to MRI-only-based target definition in radiotherapy of localized prostate cancer

PurposeTo investigate the conversion of prostate cancer radiotherapy (RT) target definition from CT-based planning into an MRI-only-based planning procedure.Materials and methodsUsing the CT- and MRI-only-based RT planning protocols, 30xa0prostate cancer patients were imaged in the RT fixation position. Two physicians delineated the prostate in both CT and T2-weighted MRI images. The CT and MRI images were coregistered based on gold seeds and anatomic borders of the prostate. The uncertainty of the coregistration, as well as differences in target volumes and uncertainty of contour delineation were investigated. Conversion of margins and dose constraints from CT- to MRI-only-based treatment planning was assessed.ResultsOn average, the uncertainty of image coregistration was 0.4u2009±u20090.5xa0mm (one standard deviation, SD), 0.9u2009±u20090.8xa0mm and 0.9u2009±u20090.9xa0mm in the lateral, anterior–posterior and base–apex direction, respectively. The average ratio of the prostate volume between CT and MRI was 1.20u2009±u20090.15 (one SD). Compared to the CT-based contours, the MRI-based contours were on average 2–7xa0mm smaller in the apex, 0–1xa0mm smaller in the rectal direction and 1–4xa0mm smaller elsewhere.ConclusionWhen converting from a CT-based planning procedure to an MRI-based one, the overall planning target volumes (PTV) are prominently reduced only in the apex. The prostate margins and dose constraints can be retained by this conversion.ZusammenfassungZielZiel unserer Studie war es, die Umstellung der Strahlentherapieplanung des Prostatakarzinoms von CT-gestützter in ausschließlich MR-gestützte Zieldefinition zu untersuchen.Material und MethodenBei 30xa0Patienten mit Prostatakarzinom wurden eine CT und eine MRT unter Planungsbedingungen durchgeführt. Zwei Untersucher konturierten die Prostata in CT- und T2-gewichteten MR-Bildern. Mit Hilfe der Position von Goldstiften und der anatomischen Grenzen der Prostata wurden die CT- und MR-Bilder koregistriert. Es wurden die Genauigkeit der Koregistrierung sowie die Unterschiede der Zielvolumina und der Konturierung gemessen. Die Konvertierung der Prostatakonturen und die Dosisbeschränkung von CT- zu ausschließlich MR-gestützter Therapieplanung wurden bewertet.ErgebnisseDie Abweichung der Koregistrierung der Bilder betrug im Durchschnitt 0,4u2009±u20090,5xa0mm (Standardabweichung: 1xa0SD) in lateraler, 0,9u2009±u20090,8xa0mm in a.-p.- und 0,9u2009±u20090,9xa0mm in der Basis-Apex-Richtung. Das durchschnittliche Verhältnis des Prostatavolumens zwischen CT und MRT war 1,20u2009±u20090,15 (1xa0SD). Die MR-basierte Konturierung war verglichen mit der CT-basierten Konturierung im Bereich des Apex der Prostata im Durchschnitt um 2–7xa0mm , in rektaler Richtung um 0–1xa0mm und in der übrigen Prostata um 1–4xa0mm kleiner.SchlussfolgerungUnsere Ergebnisse zeigen, dass durch Umstellung von CT- in MR-gestützte Strahlentherapieplanung das Planungszielvolumen nur in der Prostataspitze deutlich reduziert wird. Die Umwandlung von CT-gestützter oder CT- und MR-gestützter in ausschließlich MR-gestützte Strahlenplanung erlaubt die Beibehaltung der Prostatakonturen und der Dosisbeschränkung.

Hearing and tinnitus in head and neck cancer patients after chemoradiotherapy

Head and neck cancer patients treated with high-dose cisplatin and radiotherapy will suffer from hearing deficits. The current low-dose regimen seldom causes hearing threshold decrease. Tinnitus in this patient population has not been investigated earlier. We aimed to evaluate the possible ototoxicity of low-dose (40xa0mg/m2) weekly administered cisplatin with concomitant radiotherapy. Twenty-two patients with locally advanced head and neck cancer were prospectively recruited to participate the study after treatment recommendation for chemoradiotherapy with low-dose cisplatin and intensity-modulated radiotherapy. They filled in a Tinnitus Handicap Inventory and undertook audiologic evaluations before and after treatment. Ototoxicity was determined by >10xa0dB threshold shift at frequencies 4 and 8xa0kHz or in pure tone average. A historical cohort of nine patients treated with high-dose (100xa0mg/m2) cisplatin and radiotherapy was used for comparison. After treatment, study patients demonstrated no significant changes in their hearing over frequencies 0.5–4xa0kHz, and the threshold shifts were minor at 4 and 8xa0kHz. More than 50xa0% of patients reported no tinnitus after treatment and the remainder only had slight to moderate tinnitus causing no interference with their daily activities. In contrast, five of the nine patients having received high-dose cisplatin reported disturbing tinnitus. Further, changes in pure tone averages were exhibited in three of these patients and six had significant threshold shifts at 4 and 8xa0kHz. Head and neck cancer patients treated with concomitant intensity-modulated radiotherapy and low-dose cisplatin seem to experience only minor audiological sequelae and therefore, these patients appear to require no routine audiological monitoring. Such evaluation could be performed only when needed.

Converting from CT- to MRI-only-based target definition in radiotherapy of localized prostate cancer: A comparison between two modalities.

PurposeTo investigate the conversion of prostate cancer radiotherapy (RT) target definition from CT-based planning into an MRI-only-based planning procedure.Materials and methodsUsing the CT- and MRI-only-based RT planning protocols, 30xa0prostate cancer patients were imaged in the RT fixation position. Two physicians delineated the prostate in both CT and T2-weighted MRI images. The CT and MRI images were coregistered based on gold seeds and anatomic borders of the prostate. The uncertainty of the coregistration, as well as differences in target volumes and uncertainty of contour delineation were investigated. Conversion of margins and dose constraints from CT- to MRI-only-based treatment planning was assessed.ResultsOn average, the uncertainty of image coregistration was 0.4u2009±u20090.5xa0mm (one standard deviation, SD), 0.9u2009±u20090.8xa0mm and 0.9u2009±u20090.9xa0mm in the lateral, anterior–posterior and base–apex direction, respectively. The average ratio of the prostate volume between CT and MRI was 1.20u2009±u20090.15 (one SD). Compared to the CT-based contours, the MRI-based contours were on average 2–7xa0mm smaller in the apex, 0–1xa0mm smaller in the rectal direction and 1–4xa0mm smaller elsewhere.ConclusionWhen converting from a CT-based planning procedure to an MRI-based one, the overall planning target volumes (PTV) are prominently reduced only in the apex. The prostate margins and dose constraints can be retained by this conversion.ZusammenfassungZielZiel unserer Studie war es, die Umstellung der Strahlentherapieplanung des Prostatakarzinoms von CT-gestützter in ausschließlich MR-gestützte Zieldefinition zu untersuchen.Material und MethodenBei 30xa0Patienten mit Prostatakarzinom wurden eine CT und eine MRT unter Planungsbedingungen durchgeführt. Zwei Untersucher konturierten die Prostata in CT- und T2-gewichteten MR-Bildern. Mit Hilfe der Position von Goldstiften und der anatomischen Grenzen der Prostata wurden die CT- und MR-Bilder koregistriert. Es wurden die Genauigkeit der Koregistrierung sowie die Unterschiede der Zielvolumina und der Konturierung gemessen. Die Konvertierung der Prostatakonturen und die Dosisbeschränkung von CT- zu ausschließlich MR-gestützter Therapieplanung wurden bewertet.ErgebnisseDie Abweichung der Koregistrierung der Bilder betrug im Durchschnitt 0,4u2009±u20090,5xa0mm (Standardabweichung: 1xa0SD) in lateraler, 0,9u2009±u20090,8xa0mm in a.-p.- und 0,9u2009±u20090,9xa0mm in der Basis-Apex-Richtung. Das durchschnittliche Verhältnis des Prostatavolumens zwischen CT und MRT war 1,20u2009±u20090,15 (1xa0SD). Die MR-basierte Konturierung war verglichen mit der CT-basierten Konturierung im Bereich des Apex der Prostata im Durchschnitt um 2–7xa0mm , in rektaler Richtung um 0–1xa0mm und in der übrigen Prostata um 1–4xa0mm kleiner.SchlussfolgerungUnsere Ergebnisse zeigen, dass durch Umstellung von CT- in MR-gestützte Strahlentherapieplanung das Planungszielvolumen nur in der Prostataspitze deutlich reduziert wird. Die Umwandlung von CT-gestützter oder CT- und MR-gestützter in ausschließlich MR-gestützte Strahlenplanung erlaubt die Beibehaltung der Prostatakonturen und der Dosisbeschränkung.

Submandibular gland cancer: Specific features and treatment considerations

In the absence of unified treatment protocol, we evaluated the management and outcomes of submandibular gland cancers in an unselected patient series.