Kauko Saarilahti - Academia.edu (original) (raw)
Papers by Kauko Saarilahti
International Journal of Radiation Oncology*Biology*Physics, 2014
Early laryngeal cancer is usually treated with either transoral laser surgery or radiation therap... more Early laryngeal cancer is usually treated with either transoral laser surgery or radiation therapy. The quality of voice achieved with these treatments has not been compared in a randomized trial. Male patients with carcinoma limited to 1 mobile vocal cord (T1aN0M0) were randomly assigned to receive either laser surgery (n=32) or external beam radiation therapy (n=28). Surgery consisted of tumor excision with a CO2 laser with the patient under general anaesthesia. External beam radiation therapy to the larynx was delivered to a cumulative dose of 66 Gy in 2-Gy daily fractions over 6.5 weeks. Voice quality was assessed at baseline and 6 and 24 months after treatment. The main outcome measures were expert-rated voice quality on a grade, roughness, breathiness, asthenia, and strain (GRBAS) scale, videolaryngostroboscopic findings, and the patients' self-rated voice quality and its impact on activities of daily living. Overall voice quality between the groups was rated similar, but voice was more breathy and the glottal gap was wider in patients treated with laser surgery than in those who received radiation therapy. Patients treated with radiation therapy reported less hoarseness-related inconvenience in daily living 2 years after treatment. Three patients in each group had local cancer recurrence within 2 years from randomization. Radiation therapy may be the treatment of choice for patients whose requirements for voice quality are demanding. Overall voice quality was similar in both treatment groups, however, indicating a need for careful consideration of patient-related factors in the choice of a treatment option.
We estimated accuracy requirements for dose and position of the major salivary glands in head and... more We estimated accuracy requirements for dose and position of the major salivary glands in head and neck intensity-modulated radiotherapy (IMRT) based on the dose response characteristics of the glands obtained by using the sigmoidal dose response model. Dose response of the parotid and submandibular salivary glands was determined for 25 head and neck cancer patients treated by IMRT. Individual salivary gland functions were assessed by scintigraphy before and 6months after radiotherapy. Accuracy requirements were estimated by using the maximal slope of the fitted dose response model and average value of the dose gradients within the glands. In addition, systematic and random set-up errors were estimated for each patient by at least weekly portal imaging. We investigated the changes in the salivary gland mean doses (D(mean)) that would have occurred without correction of patient positioning. This was done by shifting the planned isocenter according to the obtained systematic set-up error and by recalculating the dose distribution in treatment planning system (TPS). The maximal slope and D(50) values of the dose response model were -0.0411/Gy and 30.4Gy, respectively. The results suggested that spared fraction of individual salivary gland function can be estimated with an accuracy of +/-10%, if actual D(mean) of the gland is within +/-2.4Gy with the planned value. On the average, this was achieved with maximal systematic positional 3D shift of 3.0mm for the parotid glands and 2.7mm for the submandibular glands. The magnitude of systematic 1D set-up errors was 1.7+/-1.3mm (mean+/-SD) while that of systematic 3D errors was 3.4+/-1.6mm. The SD of random set-up errors was 1.5mm. The magnitude of D(mean) shifts due to set-up errors was 1.5+/-1.4Gy. The steepness of dose gradients within the glands was 0.8+/-0.5Gy/mm in the most critical direction (toward the glands). When substantial part of salivary gland function is intended to be spared in head and neck IMRT, narrow dosimetric and positional tolerances should be adopted for the major salivary glands due to steep dose response curve obtained for the glands.
Radiotherapy and Oncology, 2008
To evaluate salivary gland scintigraphy in prediction of salivary flow following radiation therap... more To evaluate salivary gland scintigraphy in prediction of salivary flow following radiation therapy. Twenty patients diagnosed with head and neck cancer were treated with intensity modulated radiation therapy with an intention to spare the salivary gland function. The total quantitative saliva secretion was measured prior to and 6 and 12 months after therapy, and the function of the major salivary glands was monitored using Tc-99m-pertechnetate scintigraphy. Two models were designed for prediction of the post-treatment salivary flow: an average model, based on the average proportions of saliva produced by each of the four major glands in healthy subjects, and an individual model, based on saliva produced by each gland as measured by scintigraphy prior to therapy. These models were compared with volume-based (Lyman) normal tissue complication probability models using two published sets of model parameters. The D(50) for the parotid and the submandibular gland function assessed at 6 and 12 months after radiotherapy was approximately 39Gy. The scintigraphy-based individual model predicted well the measured post-treatment saliva flow rates. The correlation coefficient between the predicted stimulated and the measured saliva flow rate was 0.77 (p<0.0001) at 6 months and 0.55 (p=0.034) at 12 months after completion of radiotherapy. The relative changes in unstimulated and stimulated salivary flow rates showed similar dependency on the cumulative radiation dose. Salivary gland function assessed by scintigraphy prior to radiotherapy is useful in prediction of the residual salivary flow after radiotherapy.
To Irene have been disappointing with conventional therapy, within the range of 30-40%, and the m... more To Irene have been disappointing with conventional therapy, within the range of 30-40%, and the majority of these patients will eventually die of cancer [38, 39]. There have been numerous attempts to make treatment of these tumours more effective by modifying fractionation in radiotherapy schedules and by combining radiotherapy with chemotherapeutic agents. In head and neck cancer patients, the ultimate cause of death is most often locoregional recurrence of cancer, and therefore, it is of utmost importance to develop treatment protocols that are able to produce maximal local control figures.
Virchows Archiv : an international journal of pathology, Jan 3, 2015
This study aims to evaluate the long-term outcome of major salivary gland adenocystic carcinoma (... more 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 5 years or until death. Most of the tumours occurred in the parotid gland (n = 30, 56 %) followed by submandibular gland (n = 22, 41 %) and sublingual gland (n = 2, 4 %). Fifty-two patients (96 %) were treated with curative intent. All of these patients except one were primarily treated with surgery, and 29 patients (54 %) also received postoperative radiotherapy for their primary tumour. Two patients (4 %) received palliative radiotherapy. For those treated with curative intent, 32 patients (62 %) had disease recurrence. Twenty-four patients (75 %) had their first disease recurrence within 5 years and eight patients (25 %) later...
Duodecim; lääketieteellinen aikakauskirja, 2011
Intensity-modulated radiotherapy (IMRT) can be applied to reduce the radiation dose for healthy t... more Intensity-modulated radiotherapy (IMRT) can be applied to reduce the radiation dose for healthy tissues and lessen adverse effects. It can be used to increase the efficiency of treatment, for example by applying the radiotherapy in two small daily fractions instead of the usual one fraction, or by accelerated fractionation, in which the radiotherapy is also given twice a day, but with larger daily doses. With the exception of early-stage tumors, chemoradiotherapy has become an established treatment modality for tumors. The most commonly used cytotoxic agent is cisplatin, the second being cetuximab, a monoclonal antibody targeting cancer cells via the epidermal growth factor.
Duodecim; lääketieteellinen aikakauskirja, 2011
In Finland over the past few years approximately 100 new cases of oro- and hypopharyngeal cancer ... more In Finland over the past few years approximately 100 new cases of oro- and hypopharyngeal cancer have been diagnosed annually. Most of these are squamous cell carcinomas. The incidence of these diseases increases after age 45. Minor and nonspecific local symptoms caused by the primary tumor are common to pharyngeal cancers at the initial stage of the disease. Often the diagnosis is delayed and the search for the primary tumor is begun only after detection of neck metastases. They occur in 60 to 80% at the time of diagnosis. Among the risk factors, smoking and heavy drinking are most important.
Journal of otolaryngology - head & neck surgery = Le Journal d'oto-rhino-laryngologie et de chirurgie cervico-faciale, 2010
To examine a series of head and neck squamous cell cancer (HNSCC) patients treated with combined ... more To examine a series of head and neck squamous cell cancer (HNSCC) patients treated with combined gefitinib and chemoradiotherapy (CRT) regarding treatment efficacy and tolerability and correlation with epidermal growth factor receptor (EGFR) factors. Fifteen patients with locally advanced HNSCC were included in the study. The patients were scheduled to take gefitinib 250 mg in combination with concurrent radiotherapy (RT) +/- concomitant cisplatin. EGFR expression, activation and amplification; serum vascular endothelial growth factor (S-VEGF); and microvessel density were determined. Locoregional tumour control at 3 months was achieved in 79% of the patients. The treatment was reasonably well tolerated. A tendency toward a correlation between complete tumour response and EGFR amplification was observed (p = .057). Patients with activated EGFR did not have significantly more complete responses than patients with no EGFR activation (p = .10). The baseline S-VEGF levels seemed to be h...
Oral oncology, 2010
Chemoradiotherapy (CRT) of head and neck squamous cell carcinoma (HNSCC) is often accompanied by ... more Chemoradiotherapy (CRT) of head and neck squamous cell carcinoma (HNSCC) is often accompanied by severe mucosal reactions. We have recently shown that the single nucleotide polymorphism (SNP) rs1982073 of the TGFbeta1 gene (TGFB1) is associated with the survival of HNSCC patients who have undergone CRT. In order to evaluate possible mechanisms mediating this, we investigated if the TGFB1 polymorphism was associated with the severity of mucositis induced by CRT. Peripheral blood DNA of 34 HNSCC patients who had undergone CRT was genotyped for the SNP rs1982073 of the TGFB1. Mucositis was graded according to acute toxicity criteria of radiation therapy oncology group (RTOG). The mean follow-up time was 48 months (range, 4-115 months). We did not find a significant association between the TGFB1 polymorphism and the degree of acute mucositis (OD=2.65; 95% CI 0.50-13.89; p=0.25). The degree of acute mucositis was not connected to disease-free survival (p=0.35). However, the TGFB1 polymor...
Radiotherapy and Oncology, 2011
Background and purpose: To evaluate the benefits of adaptive radiotherapy for bladder cancer in d... more Background and purpose: To evaluate the benefits of adaptive radiotherapy for bladder cancer in decreasing irradiation of small bowel. Material and methods: Five patients with muscle invasive bladder cancer received adaptive radiotherapy to a total dose of 55.8-65 Gy with daily cone-beam computed tomography scanning. The whole bladder was treated to 45-50.4 Gy, followed by a partial bladder boost. The plan of the day was chosen from 3 to 4 pre-planned treatment plans according to the visible extent of bladder wall in cone-beam computed tomography images. Dose volume histograms for intestinal cavity volumes were constructed and compared with corresponding histograms calculated for conventional non-adaptive radiotherapy with single treatment plan of 2 cm CTV-PTV margins. CTV dose coverage in adaptive treatment technique was compared with CTV dose coverage in conventional radiotherapy. Results: The average volume of intestinal cavity receiving P45 Gy was reduced from 335 ± 106 cm 3 to 180 ± 113 cm 3 (1SD). The maximum volume of intestinal cavity spared at 45 Gy on a single patient was 240 cm 3 , while the minimum volume was 65 cm 3 . The corresponding reduction in average intestinal cavity volume receiving P45 Gy calculated for the whole bladder treatment only was 66 ± 36 cm 3 . CTV dose coverage was improved on two out of five patients and decreased on three patients. Conclusions: Adaptive radiotherapy considerably reduces dose to the small bowel, while maintaining the dose coverage of CTV at similar level when compared to the conventional treatment technique.
Clinical medicine insights. Ear, nose and throat, 2014
In many centers, (18)F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-P... more In many centers, (18)F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) is used to monitor treatment response after definitive (chemo)radiotherapy [(C)RT] for head and neck squamous cell carcinoma (HNSCC), but its usefulness remains somewhat controversial. We aimed at assessing the accuracy of FDG-PET/CT in detecting residual disease after (C)RT. All HNSCC patients with FDG-PET/CT performed to assess treatment response 10-18 weeks after definitive (C)RT at our institution during 2008-2010 were included. The patient charts were reviewed for FDG-PET/CT findings, histopathologic findings, and follow-up data. The median follow-up time for FDG-PET/CT negative patients was 26 months. Eighty-eight eligible patients were identified. The stage distribution was as follows: I, n = 1; II, n = 15; III, n = 17; IV, n = 55. The negative predictive value, positive predictive value, specificity, sensitivity, and accuracy of FDG-PET/CT in detecting residual disease wer...
Head & Neck, 2015
The purpose of this study was to acquire nationwide data on the management and outcome of larynge... more The purpose of this study was to acquire nationwide data on the management and outcome of laryngeal squamous cell carcinoma (SCC) in Finnish university hospitals over a 5-year posttreatment follow-up. All records of patients diagnosed and treated for primary laryngeal SCC during 2001 to 2005 were reviewed. Three hundred sixty-six patients with laryngeal cancer were identified, 360 of whom had laryngeal SCC. Three hundred forty-two patients with laryngeal SCC (95%) were treated with curative intent. Five-year disease-specific survival (DSS) for T1a, T1b, T2, T3, and T4 glottic SCC was 100%, 95%, 78%, 79%, and 53%, respectively. The corresponding figures for T1 to T4 supraglottic SCC were 68%, 54%, 72%, and 59%. Results of this nationwide study give a general overview of the outcome of unselected patients treated with unified guidelines. Patients with T2 tumors, usually treated with radiotherapy (RT), had a worse prognosis than expected. This patient group warrants further investigation and possibly treatment intensification. © 2015 Wiley Periodicals, Inc. Head Neck, 2015.
International Journal of Radiation Oncology*Biology*Physics, 2014
Early laryngeal cancer is usually treated with either transoral laser surgery or radiation therap... more Early laryngeal cancer is usually treated with either transoral laser surgery or radiation therapy. The quality of voice achieved with these treatments has not been compared in a randomized trial. Male patients with carcinoma limited to 1 mobile vocal cord (T1aN0M0) were randomly assigned to receive either laser surgery (n=32) or external beam radiation therapy (n=28). Surgery consisted of tumor excision with a CO2 laser with the patient under general anaesthesia. External beam radiation therapy to the larynx was delivered to a cumulative dose of 66 Gy in 2-Gy daily fractions over 6.5 weeks. Voice quality was assessed at baseline and 6 and 24 months after treatment. The main outcome measures were expert-rated voice quality on a grade, roughness, breathiness, asthenia, and strain (GRBAS) scale, videolaryngostroboscopic findings, and the patients' self-rated voice quality and its impact on activities of daily living. Overall voice quality between the groups was rated similar, but voice was more breathy and the glottal gap was wider in patients treated with laser surgery than in those who received radiation therapy. Patients treated with radiation therapy reported less hoarseness-related inconvenience in daily living 2 years after treatment. Three patients in each group had local cancer recurrence within 2 years from randomization. Radiation therapy may be the treatment of choice for patients whose requirements for voice quality are demanding. Overall voice quality was similar in both treatment groups, however, indicating a need for careful consideration of patient-related factors in the choice of a treatment option.
Radiotherapy and Oncology, 2011
Eighty-three patients with oropharyngeal, hypopharyngeal or laryngeal cancer were treated with co... more Eighty-three patients with oropharyngeal, hypopharyngeal or laryngeal cancer were treated with concomitant cisplatin 40 mg/m(2) once a week during the radiotherapy and IMRT up to a total dose of 70 Gy. The 2-year rate of local control, overall survival and disease specific survival were 84%, 82% and 89%, respectively. The corresponding 5-year Kaplan-Meier estimates were 79%, 69% and 76%.
Radiotherapy and Oncology, 2005
To investigate the salivary gland function following intensity modulated radiotherapy (IMRT) for ... more To investigate the salivary gland function following intensity modulated radiotherapy (IMRT) for head and neck cancer. Seventeen patients with oropharyngeal (n=11) or nasopharyngeal (n=6) carcinoma located adjacent to the major salivary glands were treated with IMRT with an emphasis to spare the salivary glands from high-dose irradiation and to reduce the risk of postirradiation xerostomy. Three patients had stage 2, 4 stage III, and 10 stage IVA cancer. The total basal and stimulated saliva flow rates were measured before the treatment, and 6 and 12 months after radiotherapy. The median basal saliva flow rate measured before radiation treatment was 0.13 mL/min, and at 6 and 12 months after the completion of IMRT 0.04 mL/min and 0.07 mL/min, respectively. The corresponding median stimulated saliva flow rates were 0.49 mL/min, 0.33 mL/min, and 0.45 mL, respectively. The D50 for an impaired stimulated parotid gland saliva flow rate was 25.5 Gy. Only two (12%) patients developed grade 3 and none grade 4 xerostomia during a median follow-up of 24 months (range, 12-40 months). No patients had locoregional cancer recurrence following IMRT. The results suggest that much of the salivary gland function can be maintained with IMRT without jeopardizing the local control rate in the treatment of locally advanced oropharynx or nasopharynx carcinoma.
Value in Health, 2011
OBJECTIVES: The incidence of prostate cancer has increased during the last two decades. Part of t... more OBJECTIVES: The incidence of prostate cancer has increased during the last two decades. Part of this increase has been attributed to prostate specific antigen (PSA) testing. As a consequence of testing many patients enter treatment at an early stage of the disease. This might be reflected in their health-related quality of life. METHODS: An ongoing observational follow-up study using the 15D generic health-related quality of life (HRQoL) instrument. Patients are asked to fill in the HRQoL questionnaire at baseline and 3, 6 and 12 months after entering treatment, and results are compared with those of an age-standardized general population sample. RESULTS: So far, 587 patients (mean age 66 years) have been assessed at baseline and 336 have completed the one-year follow-up. The mean HRQoL score (on a 0-1 scale) of the patients at baseline was statistically significantly better than that of the general population (0.904 vs. 0.874, p Ͻ 0.001). Furthermore, the patients were statistically significantly better off than the population on 9 of the 15 dimensions of the HRQoL instrument. Only the dimensions of elimination (i.e. urinating)(p Ͻ 0.001) and sexual function (p Ͻ 0.05) showed statistically significantly worse levels in the patients than in the general population. In patients having completed the one-year follow-up, the total HRQoL score fell from 0.913 to 0.886 (p
![Research paper thumbnail of Erratum to “Sparing of the submandibular glands by intensity modulated radiotherapy in the treatment of head and neck cancer” [Radiother. Oncol. 78 (2006) 270–275]](https://attachments.academia-assets.com/39168443/thumbnails/1.jpg)
](Radiotherapy and Oncology, 2006
Radiotherapy and Oncology, 2006
The submandibular glands produce most of the unstimulated saliva output and are the key in preven... more The submandibular glands produce most of the unstimulated saliva output and are the key in prevention of radiation-related xerostomia. We investigated whether sparing of the submandibular function is feasible with intensity modulated radiotherapy (IMRT). Thirty-six patients diagnosed with head and neck cancer were treated with IMRT and had at least one parotid gland excluded from the planning target volume. In a subset, of these patients (n=18) where the risk of cancer recurrence in the contralateral submandibular region was judged low, the contralateral submandibular gland was spared from full-dose irradiation. The total unstimulated and stimulated salivary flow rates and adverse effects were monitored. Twelve months following IMRT mean unstimulated saliva flow was 60% of the baseline value among patients who had one submandibular gland spared and 25% among those who did not (P=0.006). Patients whose contralateral submandibular was spared reported less grade two or three xerostomia (4 vs. 11; P=0.018), and used less saliva substitutes. No cancer recurrences were detected at the vicinity of the spared glands during a median follow-up time of 31 months. Submandibular gland sparing with IMRT is safe in selected patients treated for head and neck cancer. It is effective in prevention of radiation-associated xerostomia.
Radiotherapy and Oncology, 1998
Because opinions on the significance of repopulation during radiotherapy of T1 laryngeal cancer v... more Because opinions on the significance of repopulation during radiotherapy of T1 laryngeal cancer vary, we have estimated the effective rate of tumour cell repopulation during radiotherapy in patients with T1 laryngeal cancer. One hundred seventeen consecutive patients with T1 laryngeal cancer were treated from 1982 to 1993 by radical radiotherapy alone either as continuous (n = 28) or split-course treatment (n = 89). The logit method of the linear-quadratic formula for local control at 3 years was used to examine the effect of treatment time on local control. The analysis was made for all patients to obtain a wide range of overall treatment times. The 3-year overall survival rate was 76% and the 3-year local control rate was 85% (range 82-88%). The local control rates were 95% (range 94-96%) for the continuous and 81% (range 75-91%) for the split-course therapy groups, respectively. The results showed a mean Dprolif value at the steepest part of the response versus time curve of 0.48 Gy/day for local control at 3 years although this was not statistically significant. The trade-off of dose required to compensate for a 1 week increase in treatment time for local control at the 90% level achieved at 3 years was calculated to be 3.5 Gy. The present results suggest that repopulation should be taken into account even when treating small T1 laryngeal cancer and that protraction of the overall treatment time should be avoided.
Radiotherapy and Oncology, 2011
International Journal of Radiation Oncology*Biology*Physics, 2014
Early laryngeal cancer is usually treated with either transoral laser surgery or radiation therap... more Early laryngeal cancer is usually treated with either transoral laser surgery or radiation therapy. The quality of voice achieved with these treatments has not been compared in a randomized trial. Male patients with carcinoma limited to 1 mobile vocal cord (T1aN0M0) were randomly assigned to receive either laser surgery (n=32) or external beam radiation therapy (n=28). Surgery consisted of tumor excision with a CO2 laser with the patient under general anaesthesia. External beam radiation therapy to the larynx was delivered to a cumulative dose of 66 Gy in 2-Gy daily fractions over 6.5 weeks. Voice quality was assessed at baseline and 6 and 24 months after treatment. The main outcome measures were expert-rated voice quality on a grade, roughness, breathiness, asthenia, and strain (GRBAS) scale, videolaryngostroboscopic findings, and the patients' self-rated voice quality and its impact on activities of daily living. Overall voice quality between the groups was rated similar, but voice was more breathy and the glottal gap was wider in patients treated with laser surgery than in those who received radiation therapy. Patients treated with radiation therapy reported less hoarseness-related inconvenience in daily living 2 years after treatment. Three patients in each group had local cancer recurrence within 2 years from randomization. Radiation therapy may be the treatment of choice for patients whose requirements for voice quality are demanding. Overall voice quality was similar in both treatment groups, however, indicating a need for careful consideration of patient-related factors in the choice of a treatment option.
We estimated accuracy requirements for dose and position of the major salivary glands in head and... more We estimated accuracy requirements for dose and position of the major salivary glands in head and neck intensity-modulated radiotherapy (IMRT) based on the dose response characteristics of the glands obtained by using the sigmoidal dose response model. Dose response of the parotid and submandibular salivary glands was determined for 25 head and neck cancer patients treated by IMRT. Individual salivary gland functions were assessed by scintigraphy before and 6months after radiotherapy. Accuracy requirements were estimated by using the maximal slope of the fitted dose response model and average value of the dose gradients within the glands. In addition, systematic and random set-up errors were estimated for each patient by at least weekly portal imaging. We investigated the changes in the salivary gland mean doses (D(mean)) that would have occurred without correction of patient positioning. This was done by shifting the planned isocenter according to the obtained systematic set-up error and by recalculating the dose distribution in treatment planning system (TPS). The maximal slope and D(50) values of the dose response model were -0.0411/Gy and 30.4Gy, respectively. The results suggested that spared fraction of individual salivary gland function can be estimated with an accuracy of +/-10%, if actual D(mean) of the gland is within +/-2.4Gy with the planned value. On the average, this was achieved with maximal systematic positional 3D shift of 3.0mm for the parotid glands and 2.7mm for the submandibular glands. The magnitude of systematic 1D set-up errors was 1.7+/-1.3mm (mean+/-SD) while that of systematic 3D errors was 3.4+/-1.6mm. The SD of random set-up errors was 1.5mm. The magnitude of D(mean) shifts due to set-up errors was 1.5+/-1.4Gy. The steepness of dose gradients within the glands was 0.8+/-0.5Gy/mm in the most critical direction (toward the glands). When substantial part of salivary gland function is intended to be spared in head and neck IMRT, narrow dosimetric and positional tolerances should be adopted for the major salivary glands due to steep dose response curve obtained for the glands.
Radiotherapy and Oncology, 2008
To evaluate salivary gland scintigraphy in prediction of salivary flow following radiation therap... more To evaluate salivary gland scintigraphy in prediction of salivary flow following radiation therapy. Twenty patients diagnosed with head and neck cancer were treated with intensity modulated radiation therapy with an intention to spare the salivary gland function. The total quantitative saliva secretion was measured prior to and 6 and 12 months after therapy, and the function of the major salivary glands was monitored using Tc-99m-pertechnetate scintigraphy. Two models were designed for prediction of the post-treatment salivary flow: an average model, based on the average proportions of saliva produced by each of the four major glands in healthy subjects, and an individual model, based on saliva produced by each gland as measured by scintigraphy prior to therapy. These models were compared with volume-based (Lyman) normal tissue complication probability models using two published sets of model parameters. The D(50) for the parotid and the submandibular gland function assessed at 6 and 12 months after radiotherapy was approximately 39Gy. The scintigraphy-based individual model predicted well the measured post-treatment saliva flow rates. The correlation coefficient between the predicted stimulated and the measured saliva flow rate was 0.77 (p<0.0001) at 6 months and 0.55 (p=0.034) at 12 months after completion of radiotherapy. The relative changes in unstimulated and stimulated salivary flow rates showed similar dependency on the cumulative radiation dose. Salivary gland function assessed by scintigraphy prior to radiotherapy is useful in prediction of the residual salivary flow after radiotherapy.
To Irene have been disappointing with conventional therapy, within the range of 30-40%, and the m... more To Irene have been disappointing with conventional therapy, within the range of 30-40%, and the majority of these patients will eventually die of cancer [38, 39]. There have been numerous attempts to make treatment of these tumours more effective by modifying fractionation in radiotherapy schedules and by combining radiotherapy with chemotherapeutic agents. In head and neck cancer patients, the ultimate cause of death is most often locoregional recurrence of cancer, and therefore, it is of utmost importance to develop treatment protocols that are able to produce maximal local control figures.
Virchows Archiv : an international journal of pathology, Jan 3, 2015
This study aims to evaluate the long-term outcome of major salivary gland adenocystic carcinoma (... more 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 5 years or until death. Most of the tumours occurred in the parotid gland (n = 30, 56 %) followed by submandibular gland (n = 22, 41 %) and sublingual gland (n = 2, 4 %). Fifty-two patients (96 %) were treated with curative intent. All of these patients except one were primarily treated with surgery, and 29 patients (54 %) also received postoperative radiotherapy for their primary tumour. Two patients (4 %) received palliative radiotherapy. For those treated with curative intent, 32 patients (62 %) had disease recurrence. Twenty-four patients (75 %) had their first disease recurrence within 5 years and eight patients (25 %) later...
Duodecim; lääketieteellinen aikakauskirja, 2011
Intensity-modulated radiotherapy (IMRT) can be applied to reduce the radiation dose for healthy t... more Intensity-modulated radiotherapy (IMRT) can be applied to reduce the radiation dose for healthy tissues and lessen adverse effects. It can be used to increase the efficiency of treatment, for example by applying the radiotherapy in two small daily fractions instead of the usual one fraction, or by accelerated fractionation, in which the radiotherapy is also given twice a day, but with larger daily doses. With the exception of early-stage tumors, chemoradiotherapy has become an established treatment modality for tumors. The most commonly used cytotoxic agent is cisplatin, the second being cetuximab, a monoclonal antibody targeting cancer cells via the epidermal growth factor.
Duodecim; lääketieteellinen aikakauskirja, 2011
In Finland over the past few years approximately 100 new cases of oro- and hypopharyngeal cancer ... more In Finland over the past few years approximately 100 new cases of oro- and hypopharyngeal cancer have been diagnosed annually. Most of these are squamous cell carcinomas. The incidence of these diseases increases after age 45. Minor and nonspecific local symptoms caused by the primary tumor are common to pharyngeal cancers at the initial stage of the disease. Often the diagnosis is delayed and the search for the primary tumor is begun only after detection of neck metastases. They occur in 60 to 80% at the time of diagnosis. Among the risk factors, smoking and heavy drinking are most important.
Journal of otolaryngology - head & neck surgery = Le Journal d'oto-rhino-laryngologie et de chirurgie cervico-faciale, 2010
To examine a series of head and neck squamous cell cancer (HNSCC) patients treated with combined ... more To examine a series of head and neck squamous cell cancer (HNSCC) patients treated with combined gefitinib and chemoradiotherapy (CRT) regarding treatment efficacy and tolerability and correlation with epidermal growth factor receptor (EGFR) factors. Fifteen patients with locally advanced HNSCC were included in the study. The patients were scheduled to take gefitinib 250 mg in combination with concurrent radiotherapy (RT) +/- concomitant cisplatin. EGFR expression, activation and amplification; serum vascular endothelial growth factor (S-VEGF); and microvessel density were determined. Locoregional tumour control at 3 months was achieved in 79% of the patients. The treatment was reasonably well tolerated. A tendency toward a correlation between complete tumour response and EGFR amplification was observed (p = .057). Patients with activated EGFR did not have significantly more complete responses than patients with no EGFR activation (p = .10). The baseline S-VEGF levels seemed to be h...
Oral oncology, 2010
Chemoradiotherapy (CRT) of head and neck squamous cell carcinoma (HNSCC) is often accompanied by ... more Chemoradiotherapy (CRT) of head and neck squamous cell carcinoma (HNSCC) is often accompanied by severe mucosal reactions. We have recently shown that the single nucleotide polymorphism (SNP) rs1982073 of the TGFbeta1 gene (TGFB1) is associated with the survival of HNSCC patients who have undergone CRT. In order to evaluate possible mechanisms mediating this, we investigated if the TGFB1 polymorphism was associated with the severity of mucositis induced by CRT. Peripheral blood DNA of 34 HNSCC patients who had undergone CRT was genotyped for the SNP rs1982073 of the TGFB1. Mucositis was graded according to acute toxicity criteria of radiation therapy oncology group (RTOG). The mean follow-up time was 48 months (range, 4-115 months). We did not find a significant association between the TGFB1 polymorphism and the degree of acute mucositis (OD=2.65; 95% CI 0.50-13.89; p=0.25). The degree of acute mucositis was not connected to disease-free survival (p=0.35). However, the TGFB1 polymor...
Radiotherapy and Oncology, 2011
Background and purpose: To evaluate the benefits of adaptive radiotherapy for bladder cancer in d... more Background and purpose: To evaluate the benefits of adaptive radiotherapy for bladder cancer in decreasing irradiation of small bowel. Material and methods: Five patients with muscle invasive bladder cancer received adaptive radiotherapy to a total dose of 55.8-65 Gy with daily cone-beam computed tomography scanning. The whole bladder was treated to 45-50.4 Gy, followed by a partial bladder boost. The plan of the day was chosen from 3 to 4 pre-planned treatment plans according to the visible extent of bladder wall in cone-beam computed tomography images. Dose volume histograms for intestinal cavity volumes were constructed and compared with corresponding histograms calculated for conventional non-adaptive radiotherapy with single treatment plan of 2 cm CTV-PTV margins. CTV dose coverage in adaptive treatment technique was compared with CTV dose coverage in conventional radiotherapy. Results: The average volume of intestinal cavity receiving P45 Gy was reduced from 335 ± 106 cm 3 to 180 ± 113 cm 3 (1SD). The maximum volume of intestinal cavity spared at 45 Gy on a single patient was 240 cm 3 , while the minimum volume was 65 cm 3 . The corresponding reduction in average intestinal cavity volume receiving P45 Gy calculated for the whole bladder treatment only was 66 ± 36 cm 3 . CTV dose coverage was improved on two out of five patients and decreased on three patients. Conclusions: Adaptive radiotherapy considerably reduces dose to the small bowel, while maintaining the dose coverage of CTV at similar level when compared to the conventional treatment technique.
Clinical medicine insights. Ear, nose and throat, 2014
In many centers, (18)F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-P... more In many centers, (18)F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) is used to monitor treatment response after definitive (chemo)radiotherapy [(C)RT] for head and neck squamous cell carcinoma (HNSCC), but its usefulness remains somewhat controversial. We aimed at assessing the accuracy of FDG-PET/CT in detecting residual disease after (C)RT. All HNSCC patients with FDG-PET/CT performed to assess treatment response 10-18 weeks after definitive (C)RT at our institution during 2008-2010 were included. The patient charts were reviewed for FDG-PET/CT findings, histopathologic findings, and follow-up data. The median follow-up time for FDG-PET/CT negative patients was 26 months. Eighty-eight eligible patients were identified. The stage distribution was as follows: I, n = 1; II, n = 15; III, n = 17; IV, n = 55. The negative predictive value, positive predictive value, specificity, sensitivity, and accuracy of FDG-PET/CT in detecting residual disease wer...
Head & Neck, 2015
The purpose of this study was to acquire nationwide data on the management and outcome of larynge... more The purpose of this study was to acquire nationwide data on the management and outcome of laryngeal squamous cell carcinoma (SCC) in Finnish university hospitals over a 5-year posttreatment follow-up. All records of patients diagnosed and treated for primary laryngeal SCC during 2001 to 2005 were reviewed. Three hundred sixty-six patients with laryngeal cancer were identified, 360 of whom had laryngeal SCC. Three hundred forty-two patients with laryngeal SCC (95%) were treated with curative intent. Five-year disease-specific survival (DSS) for T1a, T1b, T2, T3, and T4 glottic SCC was 100%, 95%, 78%, 79%, and 53%, respectively. The corresponding figures for T1 to T4 supraglottic SCC were 68%, 54%, 72%, and 59%. Results of this nationwide study give a general overview of the outcome of unselected patients treated with unified guidelines. Patients with T2 tumors, usually treated with radiotherapy (RT), had a worse prognosis than expected. This patient group warrants further investigation and possibly treatment intensification. © 2015 Wiley Periodicals, Inc. Head Neck, 2015.
International Journal of Radiation Oncology*Biology*Physics, 2014
Early laryngeal cancer is usually treated with either transoral laser surgery or radiation therap... more Early laryngeal cancer is usually treated with either transoral laser surgery or radiation therapy. The quality of voice achieved with these treatments has not been compared in a randomized trial. Male patients with carcinoma limited to 1 mobile vocal cord (T1aN0M0) were randomly assigned to receive either laser surgery (n=32) or external beam radiation therapy (n=28). Surgery consisted of tumor excision with a CO2 laser with the patient under general anaesthesia. External beam radiation therapy to the larynx was delivered to a cumulative dose of 66 Gy in 2-Gy daily fractions over 6.5 weeks. Voice quality was assessed at baseline and 6 and 24 months after treatment. The main outcome measures were expert-rated voice quality on a grade, roughness, breathiness, asthenia, and strain (GRBAS) scale, videolaryngostroboscopic findings, and the patients' self-rated voice quality and its impact on activities of daily living. Overall voice quality between the groups was rated similar, but voice was more breathy and the glottal gap was wider in patients treated with laser surgery than in those who received radiation therapy. Patients treated with radiation therapy reported less hoarseness-related inconvenience in daily living 2 years after treatment. Three patients in each group had local cancer recurrence within 2 years from randomization. Radiation therapy may be the treatment of choice for patients whose requirements for voice quality are demanding. Overall voice quality was similar in both treatment groups, however, indicating a need for careful consideration of patient-related factors in the choice of a treatment option.
Radiotherapy and Oncology, 2011
Eighty-three patients with oropharyngeal, hypopharyngeal or laryngeal cancer were treated with co... more Eighty-three patients with oropharyngeal, hypopharyngeal or laryngeal cancer were treated with concomitant cisplatin 40 mg/m(2) once a week during the radiotherapy and IMRT up to a total dose of 70 Gy. The 2-year rate of local control, overall survival and disease specific survival were 84%, 82% and 89%, respectively. The corresponding 5-year Kaplan-Meier estimates were 79%, 69% and 76%.
Radiotherapy and Oncology, 2005
To investigate the salivary gland function following intensity modulated radiotherapy (IMRT) for ... more To investigate the salivary gland function following intensity modulated radiotherapy (IMRT) for head and neck cancer. Seventeen patients with oropharyngeal (n=11) or nasopharyngeal (n=6) carcinoma located adjacent to the major salivary glands were treated with IMRT with an emphasis to spare the salivary glands from high-dose irradiation and to reduce the risk of postirradiation xerostomy. Three patients had stage 2, 4 stage III, and 10 stage IVA cancer. The total basal and stimulated saliva flow rates were measured before the treatment, and 6 and 12 months after radiotherapy. The median basal saliva flow rate measured before radiation treatment was 0.13 mL/min, and at 6 and 12 months after the completion of IMRT 0.04 mL/min and 0.07 mL/min, respectively. The corresponding median stimulated saliva flow rates were 0.49 mL/min, 0.33 mL/min, and 0.45 mL, respectively. The D50 for an impaired stimulated parotid gland saliva flow rate was 25.5 Gy. Only two (12%) patients developed grade 3 and none grade 4 xerostomia during a median follow-up of 24 months (range, 12-40 months). No patients had locoregional cancer recurrence following IMRT. The results suggest that much of the salivary gland function can be maintained with IMRT without jeopardizing the local control rate in the treatment of locally advanced oropharynx or nasopharynx carcinoma.
Value in Health, 2011
OBJECTIVES: The incidence of prostate cancer has increased during the last two decades. Part of t... more OBJECTIVES: The incidence of prostate cancer has increased during the last two decades. Part of this increase has been attributed to prostate specific antigen (PSA) testing. As a consequence of testing many patients enter treatment at an early stage of the disease. This might be reflected in their health-related quality of life. METHODS: An ongoing observational follow-up study using the 15D generic health-related quality of life (HRQoL) instrument. Patients are asked to fill in the HRQoL questionnaire at baseline and 3, 6 and 12 months after entering treatment, and results are compared with those of an age-standardized general population sample. RESULTS: So far, 587 patients (mean age 66 years) have been assessed at baseline and 336 have completed the one-year follow-up. The mean HRQoL score (on a 0-1 scale) of the patients at baseline was statistically significantly better than that of the general population (0.904 vs. 0.874, p Ͻ 0.001). Furthermore, the patients were statistically significantly better off than the population on 9 of the 15 dimensions of the HRQoL instrument. Only the dimensions of elimination (i.e. urinating)(p Ͻ 0.001) and sexual function (p Ͻ 0.05) showed statistically significantly worse levels in the patients than in the general population. In patients having completed the one-year follow-up, the total HRQoL score fell from 0.913 to 0.886 (p
Radiotherapy and Oncology, 2006
Radiotherapy and Oncology, 2006
The submandibular glands produce most of the unstimulated saliva output and are the key in preven... more The submandibular glands produce most of the unstimulated saliva output and are the key in prevention of radiation-related xerostomia. We investigated whether sparing of the submandibular function is feasible with intensity modulated radiotherapy (IMRT). Thirty-six patients diagnosed with head and neck cancer were treated with IMRT and had at least one parotid gland excluded from the planning target volume. In a subset, of these patients (n=18) where the risk of cancer recurrence in the contralateral submandibular region was judged low, the contralateral submandibular gland was spared from full-dose irradiation. The total unstimulated and stimulated salivary flow rates and adverse effects were monitored. Twelve months following IMRT mean unstimulated saliva flow was 60% of the baseline value among patients who had one submandibular gland spared and 25% among those who did not (P=0.006). Patients whose contralateral submandibular was spared reported less grade two or three xerostomia (4 vs. 11; P=0.018), and used less saliva substitutes. No cancer recurrences were detected at the vicinity of the spared glands during a median follow-up time of 31 months. Submandibular gland sparing with IMRT is safe in selected patients treated for head and neck cancer. It is effective in prevention of radiation-associated xerostomia.
Radiotherapy and Oncology, 1998
Because opinions on the significance of repopulation during radiotherapy of T1 laryngeal cancer v... more Because opinions on the significance of repopulation during radiotherapy of T1 laryngeal cancer vary, we have estimated the effective rate of tumour cell repopulation during radiotherapy in patients with T1 laryngeal cancer. One hundred seventeen consecutive patients with T1 laryngeal cancer were treated from 1982 to 1993 by radical radiotherapy alone either as continuous (n = 28) or split-course treatment (n = 89). The logit method of the linear-quadratic formula for local control at 3 years was used to examine the effect of treatment time on local control. The analysis was made for all patients to obtain a wide range of overall treatment times. The 3-year overall survival rate was 76% and the 3-year local control rate was 85% (range 82-88%). The local control rates were 95% (range 94-96%) for the continuous and 81% (range 75-91%) for the split-course therapy groups, respectively. The results showed a mean Dprolif value at the steepest part of the response versus time curve of 0.48 Gy/day for local control at 3 years although this was not statistically significant. The trade-off of dose required to compensate for a 1 week increase in treatment time for local control at the 90% level achieved at 3 years was calculated to be 3.5 Gy. The present results suggest that repopulation should be taken into account even when treating small T1 laryngeal cancer and that protraction of the overall treatment time should be avoided.
Radiotherapy and Oncology, 2011