Long-term disease outcome and volume-based decision strategy in a large cohort of multiple brain metastases treated with a mono-isocentric linac-based Stereotactic Radiosurgery technique

Purpose Radiosurgery (SRS) is an effective treatment option for brain metastases (BMs). Long-term results of the first worldwide experience with a mono-isocentric, non-coplanar, linac-based stereotactic technique in the treatment of multiple BMs are reported. Methods patients with multiple BMs, life expectancy > 3 months, and good performance status (≤ 2) were treated with simultaneous SRS with volumetric modulated arc technique. Data were retrospectively evaluated. Results 172 patients accounting for 1079 BMs were treated at our institution from 2017 to 2020. The median number of treated metastases was 4 (range 2–22). Primary tumor histology was: lung (44.8%), breast (32%), and melanoma (9.4%). The 2-year LPFS was 71.6%, respectively. A biological effective dose (BED) ≥ 51.3 Gy10 correlated with higher local control. Uncontrolled systemic disease and melanoma histology were independent prognostic factors correlated with decreased iPFS. Patients with > 10 BMs had a trend towards shorter iPFS (p = 0.055). 31 patients received multiple SRS courses (2–7) in case of intracranial progression. The median iOS was 22.4 months. Brainstem metastases and total PTV > 7.1 cc correlated with shorter iOS. The 1- and 2-year WBRT-free survival was 83.2% and 61.1%, respectively. Conclusion Long-term results in a large patient population treated with a mono-isocentric, dedicated technique demonstrated its effectiveness and safety also in the case of multiple courses. The shortened treatment time and the possibility to safely spare healthy brain tissue allows the safe treatment of patients with a large number of metastases and to deliver multiple courses of SRS. In selected cases, the administration of WBRT can be delayed (AU)

Long-term disease outcome and volume-based decision strategy in a large cohort of multiple brain metastases treated with a mono-isocentric linac-based Stereotactic Radiosurgery technique.

PURPOSE: Radiosurgery (SRS) is an effective treatment option for brain metastases (BMs). Long-term results of the first worldwide experience with a mono-isocentric, non-coplanar, linac-based stereotactic technique in the treatment of multiple BMs are reported. METHODS: patients with multiple BMs, life expectancy > 3 months, and good performance status (≤ 2) were treated with simultaneous SRS with volumetric modulated arc technique. Data were retrospectively evaluated. RESULTS: 172 patients accounting for 1079 BMs were treated at our institution from 2017 to 2020. The median number of treated metastases was 4 (range 2-22). Primary tumor histology was: lung (44.8%), breast (32%), and melanoma (9.4%). The 2-year LPFS was 71.6%, respectively. A biological effective dose (BED) ≥ 51.3 Gy10 correlated with higher local control. Uncontrolled systemic disease and melanoma histology were independent prognostic factors correlated with decreased iPFS. Patients with > 10 BMs had a trend towards shorter iPFS (p = 0.055). 31 patients received multiple SRS courses (2-7) in case of intracranial progression. The median iOS was 22.4 months. Brainstem metastases and total PTV > 7.1 cc correlated with shorter iOS. The 1- and 2-year WBRT-free survival was 83.2% and 61.1%, respectively. CONCLUSION: Long-term results in a large patient population treated with a mono-isocentric, dedicated technique demonstrated its effectiveness and safety also in the case of multiple courses. The shortened treatment time and the possibility to safely spare healthy brain tissue allows the safe treatment of patients with a large number of metastases and to deliver multiple courses of SRS. In selected cases, the administration of WBRT can be delayed.

Fentanyl pectin nasal spray for painful mucositis in head and neck cancers during intensity-modulated radiation therapy with or without chemotherapy

Purpose. The aim of the current analysis was to evaluate the effectiveness and tolerability of rapid onset opioid in a cohort of head and neck cancer (HNC) patients affected by painful mucositis influencing swallowing function during RT ± ChT with definitive or adjuvant intent. Methods. A retrospective analysis was conduct on HNC patients during RT ± ChT that received fentanyl pectin na sal spray (FPNS) for incidental BTP due to painful mucositis 13 min before the main meals. The period of observation has been 90 days starting from the beginning of RT ± ChT. Results. Forty HNC patients with incidental BTP due to painful mucositis treated with FPNS were analyzed. The mean NRS of untreated episodes of BTP was 5.73 ± 1.54 decreasing to 2.25 ± 2.45 with FPNS (median dose 100 mcg). During the pain treatment, the number of meals increased from 2.08 ± 0.35 to 2.868 ± 0.4 (p = 0.000), and the BMI remained stable (from 25.086 ± 3.292 to 25.034 ± 3.090; p = 0.448). The 94.9% of patients was satisfied or very satisfied for the rapidity of the effect, and 97.4% for the easiness and convenience in the use. Conclusions. FPNS showed an acceptable safety activity profile in predictable BTP due to painful mucositis in HNC patients during RT ± ChT. FPNS was also effective in reducing the mucositis sequelae and allowing the completion of RT scheduled scheme. Moreover, patients declared satisfaction in terms of ease of use (AU)

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Radiation dose intensification in pre-operative chemo-radiotherapy for locally advanced rectal cancer

Background. To assess the role of radiation dose intensification with simultaneous integrated boost guided by 18-FDG-PET/CT in pre-operative chemo-radiotherapy (ChT-RT) for locally advanced rectal cancer. Methods. A prospective study was approved by the Internal Review Board. Inclusion criteria were: age >18 years old, World Health Organization performance status of 0-1, locally advanced histologically proven adenocarcinoma of the rectum within 10 cm of the anal verge, signed specific informed consent. High-dose volumes were defined including the hyper-metabolic areas of 18-FDG-PET/CT of primary tumor and the corresponding mesorectum and/or pelvic nodes with at least a standardized uptake values (SUV) of 5. A dose of 60 Gy/30 fractions was delivered. A total dose of 54 Gy/30 fractions was delivered to prophylactic areas. Capecitabine was administered concomitantly with RT for a dose of 825 mg/mq twice daily for 5 days/every week. Results. Between September 2011 and July 2015 fortypatients were recruited. At the time of the analysis, median follow up was 20 months (range 5-51). The median interval from the end of ChT-RT to surgery was 9 weeks (range 8-12). Thirty-seven patients (92.5 %) were submitted to sphincter preservation. Tumor Regression Grade (Mandard scale) was recorded as follows: grade 1 in 7 (17.5 %), grade 2 in 17 (42.5 %), grade 3 in 15 (37.5 %) and grade 4 in 1 (2.5 %). Post-surgical circumferential resection margin was negative in all patients. A tumor downstaging was reported in 62.5 % (95 % CI: 0.78-0.47). A nodes downstaging was registered in 85 % (95 % CI: 0.55-0.25). 18-FDG-PET/CT was not able to predict pCR. No correlation was found between pre-treatment SUV-max values and pCR. A metabolic tumor volume >127 cc was related to ypT ≥2 (p 0.01). Patients with TRG >2 had higher tumor lesion glycolysis values (p 0.05). Conclusion. Preliminary results did not confirm some advantages in terms of primary tumor downstaging/downsizing compared to conventional schedules reported in historical series. The role of 18-FDG-PET/CT in neoadjuvant rectal cancer management needs to be confirmed in further investigations. Long terms results are necessary (AU)

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Radiation dose intensification in pre-operative chemo-radiotherapy for locally advanced rectal cancer.

BACKGROUND: To assess the role of radiation dose intensification with simultaneous integrated boost guided by 18-FDG-PET/CT in pre-operative chemo-radiotherapy (ChT-RT) for locally advanced rectal cancer. METHODS: A prospective study was approved by the Internal Review Board. Inclusion criteria were: age >18 years old, World Health Organization performance status of 0-1, locally advanced histologically proven adenocarcinoma of the rectum within 10 cm of the anal verge, signed specific informed consent. High-dose volumes were defined including the hyper-metabolic areas of 18-FDG-PET/CT of primary tumor and the corresponding mesorectum and/or pelvic nodes with at least a standardized uptake values (SUV) of 5. A dose of 60 Gy/30 fractions was delivered. A total dose of 54 Gy/30 fractions was delivered to prophylactic areas. Capecitabine was administered concomitantly with RT for a dose of 825 mg/mq twice daily for 5 days/every week. RESULTS: Between September 2011 and July 2015 fortypatients were recruited. At the time of the analysis, median follow up was 20 months (range 5-51). The median interval from the end of ChT-RT to surgery was 9 weeks (range 8-12). Thirty-seven patients (92.5 %) were submitted to sphincter preservation. Tumor Regression Grade (Mandard scale) was recorded as follows: grade 1 in 7 (17.5 %), grade 2 in 17 (42.5 %), grade 3 in 15 (37.5 %) and grade 4 in 1 (2.5 %). Post-surgical circumferential resection margin was negative in all patients. A tumor downstaging was reported in 62.5 % (95 % CI: 0.78-0.47). A nodes downstaging was registered in 85 % (95 % CI: 0.55-0.25). 18-FDG-PET/CT was not able to predict pCR. No correlation was found between pre-treatment SUV-max values and pCR. A metabolic tumor volume >127 cc was related to ypT ≥2 (p 0.01). Patients with TRG >2 had higher tumor lesion glycolysis values (p 0.05). CONCLUSION: Preliminary results did not confirm some advantages in terms of primary tumor downstaging/downsizing compared to conventional schedules reported in historical series. The role of 18-FDG-PET/CT in neoadjuvant rectal cancer management needs to be confirmed in further investigations. Long terms results are necessary.

Fentanyl pectin nasal spray for painful mucositis in head and neck cancers during intensity-modulated radiation therapy with or without chemotherapy.

PURPOSE: The aim of the current analysis was to evaluate the effectiveness and tolerability of rapid onset opioid in a cohort of head and neck cancer (HNC) patients affected by painful mucositis influencing swallowing function during RT ± ChT with definitive or adjuvant intent. METHODS: A retrospective analysis was conduct on HNC patients during RT ± ChT that received fentanyl pectin na sal spray (FPNS) for incidental BTP due to painful mucositis 13 min before the main meals. The period of observation has been 90 days starting from the beginning of RT ± ChT. RESULTS: Forty HNC patients with incidental BTP due to painful mucositis treated with FPNS were analyzed. The mean NRS of untreated episodes of BTP was 5.73 ± 1.54 decreasing to 2.25 ± 2.45 with FPNS (median dose 100 mcg). During the pain treatment, the number of meals increased from 2.08 ± 0.35 to 2.868 ± 0.4 (p = 0.000), and the BMI remained stable (from 25.086 ± 3.292 to 25.034 ± 3.090; p = 0.448). The 94.9% of patients was satisfied or very satisfied for the rapidity of the effect, and 97.4% for the easiness and convenience in the use. CONCLUSIONS: FPNS showed an acceptable safety activity profile in predictable BTP due to painful mucositis in HNC patients during RT ± ChT. FPNS was also effective in reducing the mucositis sequelae and allowing the completion of RT scheduled scheme. Moreover, patients declared satisfaction in terms of ease of use.

Cachexia induces head and neck changes in locally advanced oropharyngeal carcinoma during definitive cisplatin and image-guided volumetric-modulated arc radiation therapy.

BACKGROUND/OBJECTIVES: Cancer cachexia is a syndrome characterized by weight loss (WL) and sarcopenia. Aim of the study was to assess the impact of cachexia on head and neck changes during definitive cisplatin and image-guided volumetric-modulated arc radiation therapy in a series of locally advanced oropharyngeal cancer. SUBJECTS/METHODS: Volume variations of sternocleidomastoid muscle (SCM) were considered as surrogate of muscle changes related to sarcopenia. Two head and neck diameters, encompassing the cranial limits of II and III nodal levels (defined as 'head diameter' and 'neck diameter', respectively), were measured. All parameters were defined retrospectively by means of on-board cone beam computed tomography images at 1-8th to 15-22th and at last fraction (fx) of radiotherapy (RT). Cachexia was defined as WL >5% during treatment. Analysis was conducted correlating the parameter changes with three WL ranges: <5, 5-9 and>10%. RESULTS: Thirty patients were evaluated. One hundred and fifty contoured SCMs and three hundred diameters were collected. Median WL was 6.5% (range, 0-16%). The most significant SCM shrinkage was recorded at 15th fx (mean 1.6 cc) related to WL 5-9% and WL >10% (P 0.001). For 'head diameter', the peak reduction was recorded at the 15th fx (mean 8 mm), statistically correlated to WL >10% (P 0.001). The peak reduction in 'neck diameter' was registered at the 22th fx (mean 6 mm), with a gradual reduction until the end of treatment for WL >5%. CONCLUSIONS: In a homogeneous cohort of patients, present study quantified the impact of cachexia on head and neck changes. Present data could provide adaptive RT implications for further investigations.

The impact of prostate gland dimension in genitourinary toxicity after definitive prostate cancer treatment with moderate hypofractionation and volumetric modulated arc radiation therapy

Purpose: To analyze clinical-dosimetric predictors of genitourinary (GU) toxicity in a cohort of prostate cancer (PC) patients treated with moderate hypofractionation and simultaneous integrated boost (SIB) using volumetric modulated arc therapy (VMAT) technique. Materials and methods: 60 patients were selected. Patients were stratified into low (43 %), intermediate (30 %) and high-risk (27 %) groups. Low-risk patients received 73.5 Gy to PTV1; intermediate-risk received 73.5 Gy to PTV1 and 60 Gy to PTV2; high-risk received 73.5 Gy to PTV1, 60 Gy to PTV2, and 54 Gy to PTV3. All patients were treated in 30 fractions. Androgen deprivation therapy (ADT) was prescribed upfront in intermediate and high-risk categories. Toxicity was scored according to Common Terminology Criteria for Adverse Events v4.0 scoring system. Results: Median follow-up was 30 months (range 16-36 months). GU acute toxicity was recorded as followS: G0 = 16/60 (27 %), G1 = 18/60 (30 %); G2 = 26/ 60 (43 %). GU late toxicity was recorded as follows: G0 = 20/60 (34 %); G1 = 29/60 (48 %); G2 = 11/56 (18 %). The risk of acute G2 GU toxicity was three times higher for prostate volume C80 cc. In 60 % of the patients with a prostate volume C80 cc, the first 3 weeks are at particular risk for toxicity onset. In the late setting, no statistical significance was found between GU toxicity and prostate gland dimension. Conclusion: Prostate volume C80 cc resulted a predictive factor of acute G2 GU toxicity, in moderate hypofractionation and volumetric modulated arc radiation therapy for definitive PC (AU)

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The impact of prostate gland dimension in genitourinary toxicity after definitive prostate cancer treatment with moderate hypofractionation and volumetric modulated arc radiation therapy.

PURPOSE: To analyze clinical-dosimetric predictors of genitourinary (GU) toxicity in a cohort of prostate cancer (PC) patients treated with moderate hypofractionation and simultaneous integrated boost (SIB) using volumetric modulated arc therapy (VMAT) technique. MATERIALS AND METHODS: 60 patients were selected. Patients were stratified into low (43 %), intermediate (30 %) and high-risk (27 %) groups. Low-risk patients received 73.5 Gy to PTV1; intermediate-risk received 73.5 Gy to PTV1 and 60 Gy to PTV2; high-risk received 73.5 Gy to PTV1, 60 Gy to PTV2, and 54 Gy to PTV3. All patients were treated in 30 fractions. Androgen deprivation therapy (ADT) was prescribed upfront in intermediate and high-risk categories. Toxicity was scored according to Common Terminology Criteria for Adverse Events v4.0 scoring system. RESULTS: Median follow-up was 30 months (range 16-36 months). GU acute toxicity was recorded as followS: G0 = 16/60 (27 %), G1 = 18/60 (30 %); G2 = 26/60 (43 %). GU late toxicity was recorded as follows: G0 = 20/60 (34 %); G1 = 29/60 (48 %); G2 = 11/56 (18 %). The risk of acute G2 GU toxicity was three times higher for prostate volume ≥80 cc. In 60 % of the patients with a prostate volume ≥80 cc, the first 3 weeks are at particular risk for toxicity onset. In the late setting, no statistical significance was found between GU toxicity and prostate gland dimension. CONCLUSION: Prostate volume ≥80 cc resulted a predictive factor of acute G2 GU toxicity, in moderate hypofractionation and volumetric modulated arc radiation therapy for definitive PC.

Intensity modulated radiation therapy with simultaneous integrated boost in early breast cancer irradiation. Report of feasibility and preliminary toxicity.

PURPOSE: To investigate the feasibility and tolerance in the use of adjuvant intensity modulated radiation therapy (IMRT) and simultaneous integrated boost in patients with a diagnosis of breast cancer after breast-conserving surgery. PATIENTS AND METHODS: Between September 2011 to February 2013, 112 women with a diagnosis of early breast cancer (T1-2, N0-1, M0) were treated with IMRT and simultaneous integrated boost after breast-conserving surgery in our institution. A dose of 50Gy in 25 fractions was prescribed to the whole breast and an additional dose of radiation was prescribed on the tumour bed. A dose prescription of 60Gy in 25 fractions to the tumour bed was used in patients with negative margins after surgery, whereas if the margins were close (<1mm) or positive (without a new surgical resection) a dose of 64Gy was prescribed. All patients were followed with periodic clinical evaluation. Acute and late toxicity were scored using the EORTC/RTOG radiation morbidity score system. Both patient and physician recorded cosmetic outcome evaluation with a subjective judgment scale at the time of scheduled follow-up. RESULTS: The median follow-up was 28 months (range 24-40 months). The acute skin grade toxicity during the treatment was grade 0 in 8 patients (7%), grade 1 in 80 (72%), grade 2 in 24 cases (21%). No grade 3 or higher acute skin toxicity was observed. At 12 months, skin toxicity was grade 0 in 78 patients (70%), grade 1 in 34 patients (30%). No toxicity grade 2 or higher was registered. At 24 months, skin toxicity was grade 0 in 79 patients (71%), grade 1 in 33 patients (29%). No case of grade 2 toxicity or higher was registered. The pretreatment variables correlated with skin grade 2 acute toxicity were adjuvant chemotherapy (P=0.01) and breast volume ≥700cm(3) (P=0.001). Patients with an acute skin toxicity grade 2 had a higher probability to develop late skin toxicity (P<0.0001). In the 98% of cases, patients were judged to have a good or excellent cosmetic outcome. The 2-year-overall survival and 2-year-local control were 100%. CONCLUSION: These data support the feasibility and safety of IMRT with simultaneous integrated boost in patients with a diagnosis of early breast cancer following breast-conserving surgery with acceptable acute and late treatment-related toxicity. A longer follow-up is needed to define the efficacy on outcomes.

The Shape of Parotid DVH Predicts the Entity of Gland Deformation During IMRT for Head and Neck Cancers.

The Jacobian of the deformation field of the registration between images taken during Radiotherapy is a measure of compression/expansion of the voxels within an organ. The Jacobian mean value was applied to investigate possible correlations between parotid deformation and anatomical, clinical and dosimetric parameters. Data of 84 patients were analyzed. Parotid deformation was evaluated through Jacobian maps of images taken at the start and at the end of the treatment. Several clinical, geometrical and dosimetric factors were considered. Correlation between Jacobian mean value and these parameters was assessed through Spearman's test. Univariate and multivariate logistic analyses were performed by considering as the end point the first quartile value of the Jacobian mean value. Parotid dose volume histograms were stratified according to gland deformation, assessing the most predictive dose-volume combination. At multivariate analysis, age (p = 0.02), overlap between tumor volume and parotid gland (p = 0.0006) and the parotid volume receiving more than 10 Gy (p = 0.02) were found as the best independent predictors, by considering Jacobian mean value fist quartile, the parotid volume receiving more than 10 Gy and 40 Gy were found as the most predictive dosimetric parameters. Parotid glands were divided in three different sub-groups (bad-, medium- and good dose volume histogram). The risk to have Jacobian means value lower than first quartile was 39.6% versus 19.6% versus 11.3% in these three groups. By including in the multivariate analysis this "dose volume grouping" parameter, age and bad dose volume histogram were found as the most predictive parameters for large shrinkage. The pattern of parotid deformation may be well predicted by some pre-treatment variables; a bad dose volume histogram seems the most important predictor.

Dose-volume-related dysphagia after constrictor muscles definition in head and neck cancer intensity-modulated radiation treatment.

OBJECTIVE: Dysphagia remains a side effect influencing the quality of life of patients with head and neck cancer (HNC) after radiotherapy. We evaluated the relationship between planned dose involvement and acute and late dysphagia in patients with HNC treated with intensity-modulated radiation therapy (IMRT), after a recontouring of constrictor muscles (PCs) and the cricopharyngeal muscle (CM). METHODS: Between December 2011 and December 2013, 56 patients with histologically proven HNC were treated with IMRT or volumetric-modulated arc therapy. The PCs and CM were recontoured. Correlations between acute and late toxicity and dosimetric parameters were evaluated. End points were analysed using univariate logistic regression. RESULTS: An increasing risk to develop acute dysphagia was observed when constraints to the middle PCs were not respected [mean dose (Dmean) ≥50 Gy, maximum dose (Dmax) >60 Gy, V50 >70% with a p = 0.05]. The superior PC was not correlated with acute toxicity but only with late dysphagia. The inferior PC was not correlated with dysphagia; for the CM only, Dmax >60 Gy was correlated with acute dysphagia ≥ grade 2. CONCLUSION: According to our analysis, the superior PC has a major role, being correlated with dysphagia at 3 and 6 months after treatments; the middle PC maintains this correlation only at 3 months from the beginning of radiotherapy, but it does not have influence on late dysphagia. The inferior PC and CM have a minimum impact on swallowing symptoms. ADVANCES IN KNOWLEDGE: We used recent guidelines to define dose constraints of the PCs and CM. Two results emerge in the present analysis: the superior PC influences late dysphagia, while the middle PC influences acute dysphagia.

Dosimetric predictors of dysphonia after intensity-modulated radiotherapy for oropharyngeal carcinoma.

AIMS: To investigate dosimetric predictors of voice changes after whole-field intensity-modulated radiotherapy (IMRT). MATERIALS AND METHODS: Patients treated with whole-field IMRT for oropharyngeal/unknown primary tumours were selected for the present retrospective study having grossly uninvolved larynx at the time of radiotherapy and at least one follow-up visit. Voice changes were prospectively scored at each follow-up examination according to the Common Terminology Criteria for Adverse Events (CTCAE) v3.0 scale and self-reported by two items (HN4 and HN10) of the Functional Assessment of Cancer Therapy-Head and Neck Scale (FACT-HN) questionnaire. Predictors of toxicity were investigated at logistic regression, including various patient and tumour characteristics, as well as individual dosimetric data. RESULTS: With a median follow-up of 18 months (range 3-46 months), peak CTCAE dysphonia was graded as 2 in 13 patients (10.5%), whereas 45 patients (36.3%) reported peak grade 0-1 voice changes according to FACT-HN4. Communication (FACT-HN10) was barely affected. At multivariate analysis, the mean laryngeal dose was an independent predictor of both grade 2 CTCAE dysphonia (odds ratio = 1.10, 95% confidence interval 1.01-1.20, P = 0.025) and grade 0-1 FACT-HN4 voice changes (odds ratio = 1.11, 95% confidence interval 1.04-1.18, P = 0.001). Further stratification optimised by a receiver operating characteristic (ROC) analysis showed that, to minimise the risk of grade 0-1 FACT-HN4 voice changes, the mean dose to the larynx has to be kept ≤ 49.4 Gy. CONCLUSION: Voice changes after whole-field IMRT are common, but mild, and are strictly correlated to the dose received by the uninvolved larynx; in order to minimise the risk of side-effects, the mean dose to the larynx should be kept ≤ 50 Gy.

Pattern and predictors of volumetric change of parotid glands during intensity modulated radiotherapy.

OBJECTIVE: To describe the pattern and predictors of volumetric change of parotid glands during intensity modulated radiotherapy (IMRT) for oropharyngeal cancer. METHODS: A cohort of patients undergoing weekly CT scans during dose-painted IMRT was considered. The parotid glands were contoured at the time of treatment planning (baseline) and on all subsequent scans. For a given patient, the parotid glands were labelled as higher (H) and lower (L), based on the mean dose at planning. The volume of each gland was determined for each scan and the percent change from baseline computed. Data were fit to both linear and quadratic functions. The role of selected covariates was assessed with both logistic regression and pair-wise comparison between the sides. The analyses were performed considering the whole treatment duration or each separate half. RESULTS: 85 patients, 170 glands and 565 scans were analysed. For all parotids except one, the quadratic function provided a better fit than the linear one. Moreover, according to both the logistic regression and pair-wise comparison, the cumulative mean dose of radiation is independently correlated with the parotid shrinkage during the first but not the second half of the treatment. Conversely, age and weight loss are predictors of relative parotid shrinkage during the entire course of the treatment. CONCLUSION: Parotid gland shrinkage during IMRT is not linear. Age, weight loss and radiation dose independently predict parotid shrinkage during a course of IMRT. ADVANCES IN KNOWLEDGE: The present study adds to the pathophysiology of parotid shrinkage during radiotherapy.