Dosimetric benefits of hemigland stereotactic body radiotherapy for prostate cancer: implications for focal therapy

Objective:

Compared with standard, whole-gland (WG) therapies for prostate cancer, focal approaches may provide equivalent oncologic outcomes with fewer adverse effects. The purpose of this study was to compare organ-at-risk (OAR) dosimetry between hemigland (HG) and WG stereotactic body radiotherapy (SBRT) plans.

Methods:

Volumetric-modulated arc radiotherapy-based SBRT plans were designed to treat the left HG, right HG and WG in eight patients, using five fractions of 8 Gy. OARs of interest included the contralateral HG, rectum, urinary bladder, urethra, penile bulb and contralateral neurovascular bundle.

Results:

Rectal V_80% (the percentage of a normal structure receiving a dose of 80%) and V_90% were significantly lower with HG plans than with WG plans (median values of 4.4 vs 2.5 cm³ and 2.1 vs 1.1 cm³, respectively, p < 0.05 by Student''s t-test). Bladder V_50% was also reduced significantly in HG plans (32.3 vs 17.4 cm³, p < 0.05), with a trend towards reduction of V_100% (3.4 vs 1.3 cm³, p = 0.09). Urethral maximum dose and mean doses to the penile bulb and contralateral neurovascular bundle were also reduced significantly (42.0 vs 39.7 Gy, p < 0.00001; 13.3 vs 9.2 Gy, p < 0.05; and 40.2 vs 19.3 Gy, p < 0.00001, respectively).

Conclusion:

Targeting an HG volume rather than a WG volume when delivering SBRT can offer statistically significant reductions for all OARs. Given the large magnitude of the reduction in dose to these OARs, it is anticipated that HG SBRT could offer a superior toxicity profile when compared with WG SBRT. This is likely to be most relevant in the context of salvaging a local failure after radiation therapy.

Advances in knowledge:

The dosimetric feasibility of HG SBRT is demonstrated. When compared with WG SBRT plans, the HG plans demonstrate statistically significant and large magnitude reduction in doses to the rectum, bladder, urethra, penile bulb and contralateral neurovascular bundle, suggesting the possibility of improved toxicity outcomes with HG SBRT. This is likely to be most relevant in the context of salvaging a local failure after radiation therapy.     

Simultaneously modulated accelerated radiation therapy reduces severe oesophageal toxicity in concomitant chemoradiotherapy of locally advanced non-small-cell lung cancer

Objective:

The aim of this study was to evaluate the potential of simultaneously modulated accelerated radiation therapy (SMART) to reduce the incidence of severe acute oesophagitis in the treatment of unresectable locally advanced non-small-cell lung cancer (LANSCLC).

Methods:

21 patients were treated with SMART and concomitant platinum-based chemotherapy. The prescribed doses were limited to 54 Gy at 1.8 Gy per day to the zones of presumed microscopic extent while simultaneously maintaining doses of 66 Gy at 2.2 Gy per day to the macroscopic disease. The whole treatment was delivered over 30 fractions and 6 weeks. Dosimetric parameters of SMART and the standard technique of irradiation [intensity-modulated radiation therapy (IMRT)] were compared. Acute toxicity was prospectively recorded.

Results:

The highest grade of oesophagitis was 62% (13 patients) grade 1, 33% (7 patients) grade 2 and 5% (1 patient) grade 3. Three (14%) patients experienced acute grade 2 pneumonitis. There was no grade 4 oesophageal or pulmonary toxicity. Doses to the organs at risk were significantly reduced in SMART compared with IMRT [oesophagus: V_50Gy, 28.5 Gy vs 39.9 Gy (p = 0.003); V_60Gy, 7.1 Gy vs 30.7 Gy (p = 0.003); lung: V_20Gy, 27.4 Gy vs 30.1 Gy (p = 0,002); heart: V_40Gy, 7.3 Gy vs 10.7 Gy (p = 0.006); spine: D_max, 42.4 Gy vs 46.4 Gy (p = 0.003)]. With a median follow-up of 18 months (6–33 months), the 1-year local control rate was 70% and the disease-free survival rate was 47%.

Conclusion:

SMART reduces the incidence of severe oesophagitis and improves the whole dosimetric predictors of toxicity for the lung, heart and spine.

Advances in knowledge:

Our study shows that SMART optimizes the therapeutic ratio in the treatment of LANSCLC, opening a window for dose intensification.     

Dosimetric planning study for the prevention of anal complications after post-operative whole pelvic radiotherapy in cervical cancer patients with hemorrhoids

Objective:

Radiation-induced anal toxicity can be induced by low radiation doses in patients with haemorrhoids. The object of this study was to determine the dosimetric benefits of different whole pelvic radiotherapy (WPRT) techniques in terms of dose delivered to the anal canal in post-operative patients with cervical cancer.

Methods:

The planning CT images of 10 patients with cervical cancer undergoing postoperative radiotherapy were used for comparison of three different plans. All patients had been treated using the conventional box technique WPRT (CV-WPRT), and we tried low-margin-modified WPRT (LM-WPRT), three-dimensional conformal techniques WPRT (CF-WPRT) and intensity-modulated WPRT (IM-WPRT) planning for dosimetric comparison of the anal canal, retrospectively.

Results:

Mean anal canal doses of the IM-WPRT were significantly lower (p < 0.05) than those of CV-WPRT, LM-WPRT and CF-WPRT, and V₁₀, V₂₀, V₃₀ and V₄₀ to the anal canal were also significantly lower for IM-WPRT (p < 0.05). The proportion of planning target volumes (PTVs) that received ≥98% of the prescribed dose for all plans was >99%, and the proportion that received ≥108% of the prescribed dose for IM-WPRT was <2%. Volumes of bladders and rectums that received ≥30 or ≥40 Gy were significantly lower for IM-WPRT than for three of the four-field WPRT plans (p = 0.000).

Conclusion:

IM-WPRT can significantly reduce radiation dose delivered to the anal canal and does not compromise PTV coverage. In patients with haemorrhoids, IM-WPRT may be of value for the prevention of anal complications.

Advances in knowledge:

Although tolerance of the anal canal tends to be ignored in patients undergoing post-operative WPRT, patients with haemorrhoids may suffer complications at low radiation doses. The present study shows IM-WPRT can be meaningful in these patients.     

Optimizing the flattening filter free beam selection in RapidArc?-based stereotactic body radiotherapy for Stage I lung cancer

Objective:

To optimize the flattening filter-free (FFF) beam selection in stereotactic body radiotherapy (SBRT) treatment for Stage I lung cancer in different fraction schemes.

Methods:

Treatment plans from 12 patients suffering from Stage I lung cancer were designed using the 6XFFF and 10XFFF beams in different fraction schemes of 4 × 12, 3 × 18 and 1 × 34 Gy. Plans were evaluated mainly in terms of organs at risk (OARs) sparing, normal tissue complication probability (NTCP) estimation and treatment efficiency.

Results:

Compared with the 10XFFF beam, 6XFFF beam showed statistically significant lower dose to all the OARs investigated. The percentage of NTCP reduction for both lung and chest wall was about 10% in the fraction schemes of 4 × 12 and 3 × 18 Gy, whereas only 7.4% and 2.6% was obtained in the 1 × 34 Gy scheme. For oesophagus, heart and spinal cord, the reduction was greater with the 6XFFF beam, but their absolute estimates were <10⁻⁶%. The mean beam-on time for 6XFFF and 10XFFF beams at 4 × 12, 3 × 18 and 1 × 34 Gy schemes were 2.2 ± 0.2 vs 1.5 ± 0.1, 3.3 ± 0.9 vs 2.0 ± 0.5 and 6.3 ± 0.9 vs 3.5 ± 0.4 min, respectively.

Conclusion:

The 6XFFF beam obtains better OARs sparing and lower incidence of NTCP in SBRT treatment of Stage I lung cancer, whereas the 10XFFF beam improves the treatment efficiency. To balance the OARs sparing and intrafractional variation owing to the prolonged treatment time, the authors recommend using the 6XFFF beam in the 4 × 12 and 3 × 18 Gy schemes but the 10XFFF beam in the 1 × 34 Gy scheme.

Advances in knowledge:

This study optimizes the FFF beam selection in different fraction schemes in SBRT treatment of Stage I lung cancer.     

Patients with severe emphysema have a low risk of radiation pneumonitis following stereotactic body radiotherapy

Objective:

To evaluate the risk of radiation pneumonitis (RP) after stereotactic radiotherapy (SBRT) for patients presenting with severe pulmonary emphysema.

Methods:

This study included 40 patients with Stage I non-small-cell lung cancer who underwent SBRT, 75 Gy given in 30 fractions, at the Tokyo Medical University, Tokyo, Japan, between February 2010 and February 2013. The median age of the patients was 79 years (range, 49–90 years), and the male:female ratio was 24:16. There were 20 T1 and 20 T2 tumours. 17 patients had emphysema, 6 had slight interstitial changes on CT images and the remaining 17 had no underlying lung disease. The level of emphysema was classified into three groups according to the modified Goddard''s criteria (severe: three patients, moderate: eight patients and mild: six patients). Changes in the irradiated lung following SBRT were evaluated by CT.

Results:

On CT images, RP was detected in 34 (85%) patients, and not in 6 (15%) patients, during a median observation period of 313 days. Of the six patients, three had severe emphysema and three had no underlying lung disease. Patients with severe emphysema had lower risk of RP than those with moderate emphysema (p = 0.01), mild emphysema (p = 0.04) and no underlying lung disease (p = 0.01).

Conclusion:

Patients with severe emphysema had a low risk of RP following SBRT.

Advances in knowledge:

Little is known about the association between RP and pulmonary emphysema. Patients with severe emphysema had lower risk of RP than those with no underlying lung disease.In addition to smoking, lung cancer has various causes, including emphysema and chronic obstructive pulmonary disease (COPD), which are common with underlying lung diseases.^1,2 Thus, patients with underlying lung diseases have a high possibility of having cancer.¹ Stereotactic body radiotherapy (SBRT) for Stage I non-small-cell lung cancer (NSCLC) has an excellent overall survival rate and local control; therefore, SBRT is widely considered a cure with fewer treatment-related toxicities.³ Accordingly, an increasing number of patients with co-morbidities, especially underlying lung diseases, are undergoing SBRT.Radiation pneumonitis (RP) is the most severe adverse event of SBRT. Some potential predictors for the risk factors of RP are reported;⁴ however, little is known about the association between RP and underlying lung diseases, such as pulmonary emphysema. Thus, we evaluated the relation between RP and pulmonary emphysema following SBRT in patients with Stage I NSCLC.     

Parametrized rectal dose and associations with late toxicity in prostate cancer radiotherapy

Objective:

We investigated possible associations between planned dose–volume parameters and rectal late toxicity in 170 patients having radical prostate cancer radiotherapy.

Methods:

For each patient, the rectum was outlined from anorectal junction to sigmoid colon, and rectal dose was parametrized using dose–volume (DVH), dose–surface (DSH) and dose–line (DLH) histograms. Generation of DLHs differed from previous studies in that the rectal dose was parametrized without first unwrapping onto 2-dimensional dose–surface maps. Patient-reported outcomes were collected using a validated Later Effects in Normal Tissues Subjective, Objective, Management and Analytic questionnaire. Associations between dose and toxicity were assessed using a one-sided Mann–Whitney U test.

Results:

Associations (p < 0.05) were found between equieffective dose (EQD2₃) and late toxicity as follows: overall toxicity with DVH and DSH at 13–24 Gy; proctitis with DVH and DSH at 25–36 Gy and with DVH, DSH and DLH at 61–67 Gy; bowel urgency with DVH and DSH at 10–20 Gy. None of these associations met statistical significance following the application of a Bonferroni correction.

Conclusion:

Independently confirmed associations between rectal dose and late toxicity remain elusive. Future work to increase the accuracy of the knowledge of the rectal dose, either by accounting for interfraction and intrafraction rectal motion or via stabilization of the rectum during treatment, may be necessary to allow for improved dose–toxicity comparisons.

Advances in knowledge:

This study is the first to use parametrized DLHs to study associations with patient-reported toxicity for prostate radiotherapy showing that it is feasible to model rectal dose mapping in three dimensions.     

Volumetric-modulated arc stereotactic body radiotherapy for prostate cancer: dosimetric impact of an increased near-maximum target dose and of a rectal spacer

Objective:

In volumetric-modulated arc therapy (VMAT) prostate stereotactic body radiotherapy (SBRT), dose coverage of the planning target volume (PTV) becomes challenging when the sparing of rectum, bladder and urethra is strictly pursued. Our current 35-Gy-in-five-fraction plans only assure 33.2 Gy to ≥95% PTV (V33.2PTV ≥ 95%). Looking for an improved V33.2PTV, increased near-maximum target dose (D_2%) and prostate–rectum spacer insertion were tested.

Methods:

For 11 patients, two VMAT plans, with D_2% ≤ 37.5 Gy (Hom) or D_2% ≤ 40.2 Gy (Het), on each of two CT studies, before or after spacer insertion, were computed. All plans assured V33.2PTV ≥95%, and <1 cm³ of rectum, bladder and urethra receiving ≥35 Gy. By hypothesis testing, several dose–volume metrics for target coverage and rectal sparing were compared across the four groups of plans. The impact of spacer insertion on the fractions of rectum receiving more than 18, 28 and 32 Gy (VXr) was further tested by linear correlation analysis.

Results:

By hypothesis testing, the increased D_2% was associated with improvements in target coverage, whereas spacer insertion was associated with improvements in both target coverage and rectal VXr. By linear correlation analysis, spacer insertion was related to the reductions in rectal VXr for X ≥ 28 Gy.

Conclusion:

A slightly increased D_2% or the use of spacer insertion was each able to improve V33.2PTV. Their combined use assured V33.2PTV ≥ 98% to all our patients. Spacer insertion was further causative for improvements in rectal sparing.

Advances in knowledge:

For VMAT plans in prostate SBRT, the distinct dosimetric usefulness of increased D_2% and of the use of spacer insertion were validated in terms of target coverage and rectal sparing.     

Evaluation of hippocampus dose for patients undergoing intensity-modulated radiotherapy for nasopharyngeal carcinoma

Objective:

To evaluate the dose received by the hippocampus among patients undergoing intensity-modulated radiotherapy (IMRT) for nasopharyngeal cancer.

Methods:

10 patients with biopsy-proven, locally advanced nasopharyngeal cancer constituted the study population. The total prescribed dose to the planning target volume (PTV) was 70 Gy (D95%) delivered in 2.12-Gy daily fractions using IMRT. Using established anatomical guidelines, MRI co-registration and the assistance of a board-certified neuroradiologist, the right and left hippocampi were delineated on axial imaging from the CT scan obtained at simulation for each patient beginning at the most anterior portion of the lateral ventricle. IMRT treatment plans were generated without dose–volume constraints to the hippocampus. A range of dose–volume statistics was calculated.

Results:

The mean hippocampus volume was 6.01 ± 2.61 cm³. The mean V20 was 72.2%; V40 was 22.0%; V50 was 10.2%; and V60 was 5.5%. The average mean, minimum and maximum hippocampus doses were 30.27 Gy (range, 19.08–47.99 Gy); 17.54 Gy (range, 11.66–33.17 Gy); and 54.95 Gy (range, 35.59–75.57 Gy), respectively. The hippocampus received a maximum dose exceeding 70 Gy in 30% of cases.

Conclusion:

Our dosimetric analysis suggests that, for patients undergoing IMRT for nasopharyngeal cancer, the hippocampus routinely receives significantly high doses.

Advances in knowledge:

The hippocampus receives a fair amount of incidental radiation during treatment for nasopharyngeal cancer. Given the importance of this structure with respect to memory and neurocognitive function, consideration should be given to identifying the hippocampus as a critical organ at risk in the IMRT optimization process.Although intensity-modulated radiotherapy (IMRT) has supplanted two-dimensional and three-dimensional radiotherapies as the standard treatment for patients with head and neck cancer, it has become increasingly clear that the generation of highly conformal plans with steep fall-off gradients may come at the expense of significant doses to non-delineated extra-target organs.¹ Owing to the anatomical proximity of many head and neck cancers to the central nervous system, studies investigating the effects of radiation exposure on specific structures in the brain responsible for neurocognitive functioning may be warranted.Located within the temporal lobes, the hippocampus is a horseshoe-shaped paired structure that is a critical component of the limbic system. Its functions relate to the formation of new memories, spatial navigation and the connection of emotions and senses, such as smell and sound, to memories. Although the tolerance of this structure to radiation has yet to be fully established, it has been hypothesized that incidental exposure to this structure may contribute to both short-term toxicity, such as lack of inhibition and disequilibrium, as well as long-term memory loss.² Thus, the purpose of this study was to conduct a dosimetric analysis in patients with nasopharyngeal cancer treated by IMRT to assess incidental exposure to the hippocampus.     

Evaluation of Adrenal Masses in Lung Cancer Patients Using F-18 FDG PET/CT

Purpose

The aim of this study was to assess the diagnostic efficacy of PET/CT using various parameters for the characterization of adrenal nodules in lung cancer patients.

Methods

Sixty-one adrenal nodules in 51 lung cancer patients were evaluated. The final diagnosis was based on histology (n = 2) or imaging follow-up (n = 59, range of follow-up: 7–57 months, median 27 months). Each adrenal nodule was analyzed using four parameters of PET/CT: the maximum standardized uptake value (SUV_max), the adrenal nodule/liver ratio of the SUV (SUV ratio), Hounsfield units (HU) and size. The optimal cutoff of each parameter for the identification of metastatic nodule was determined by ROC analysis and then the diagnostic efficacy was compared among the parameters.

Results

Of the 61 adrenal nodules, 45 (73%) were considered metastasis. The optimal cutoff values of the parameters were SUV_max >2.7, SUV ratio >1.3, HU >18 and size >20 mm, respectively. The sensitivity, specificity and accuracy by SUV_max >2.7 were 88.9%, 87.5% and 88.5%, and those by SUV ratio >1.3 were 84.4%, 100% and 88.5%, respectively. The combination of SUV ratio >1.3 and HU >18 had sensitivity of 97.7%, specificity of 81.2% and accuracy of 93.4% to predict adrenal metastasis in patients with lung cancer.

Conclusion

SUV ratio from F-18 FDG PET/CT could identify the adrenal metastasis in lung cancer patients. The combination of SUV ratio and HU can improve the accuracy of differentiating benign and metastatic adrenal lesions in lung cancer patients.     

Visually stratified CT honeycombing as a survival predictor in combined pulmonary fibrosis and emphysema

Objective:

To determine whether visually stratified CT findings and pulmonary function variables are helpful in predicting mortality in patients with combined pulmonary fibrosis and emphysema (CPFE).

Methods:

We retrospectively identified 113 patients with CPFE who underwent high-resolution CT between January 2004 and December 2009. The extent of emphysema and fibrosis on CT was visually assessed using a 6- or 5-point scale, respectively. Univariate and multivariate Cox proportional regression analyses were performed to determine the prognostic value of visually stratified CT findings and pulmonary function variables in patients with CPFE. Differences in 5-year survival rates in patients with CPFE according to the extent of honeycombing were calculated using Kaplan–Meier analysis.

Results:

An increase in the extent of visually stratified honeycombing on CT [hazard ratio (HR), 1.95; p = 0.018; 95% confidence interval (CI), 1.12–3.39] and reduced diffusing capacity of lung for carbon monoxide (DLCO) (HR, 0.97; p = 0.017; 95% CI, 0.94–0.99) were independently associated with increased mortality. In patients with CPFE, the 5-year survival rate was 78.5% for <5% honeycombing, 55.7% for 5–25% honeycombing, 32% for 26–50% honeycombing and 33.3% for >50% honeycombing on CT.

Conclusion:

The >50% honeycombing on CT and reduced DLCO are important prognostic factors in CPFE.

Advances in knowledge:

Visual estimation of honeycombing extent on CT can help in the prediction of prognosis in CPFE.     

Dosimetric evaluation of compensator intensity modulation-based stereotactic body radiotherapy for Stage I non-small-cell lung cancer

Objective:

To evaluate the dosimetry of compensator intensity modulation-based stereotactic body radiotherapy (SBRT) [non-coplanar intensity-modulated radiotherapy (ncIMRT)], its use was compared with that of three-dimensional conformation-based SBRT, for patients with Stage I non-small-cell lung cancer (NSCLC).

Methods:

21 consecutive patients with Stage I NSCLC were treated with ncIMRT or SBRT at Tokyo Medical University. To compare the two techniques, ncIMRT and SBRT plans for each patient were generated, where the planning target volume (PTV) coverages were adjusted to be equivalent to each other. The prescribed dose was set as 75 Gy in 30 fractions. PTV coverage, conformity index, conformation number (CN) and homogeneity index (HI) were used to compare the two strategies.

Results:

There was no statistically significant difference between PTV coverage for the 100%, 95% and 90% dose levels in the SBRT plan and those in the ncIMRT plan. The CN values were 0.53 ± 0.13 in the SBRT plan and 0.72 ± 0.10 in the ncIMRT plan. These values were significantly better than those of the SBRT plan (p < 0.001). The HI in the ncIMRT plan was 1.04 ± 0.03%, which was also significantly better than that of SBRT.

Conclusion:

The ncIMRT plan provided superior conformity and reduced the doses to the lung for patients with Stage I NSCLC.

Advances in knowledge:

The delivery technique with compensator intensity modulation-based SBRT was evaluated. Concerning target motion, this is thought to be more robust and safer than SBRT for early-stage NSCLC.Population-based studies have shown that approximately half of patients with radically treatable Stage I to III non-small-cell lung cancer (NSCLC) have been diagnosed as Stage I.^1,2 Stereotactic body radiotherapy (SBRT) was considered to be a treatment option for patients with Stage I NSCLC who were unsuitable for surgery. In most studies, the SBRT outcomes were comparable with surgery in terms of local control and survival.^3,4 Therefore, the use of SBRT for patients with Stage I NSCLC has gradually increased in number.⁵Videtic et al⁶ first reported excellent local control for Stage I NSCLC when using SBRT based on intensity-modulated radiotherapy (IMRT). Recently, a new type of IMRT named volumetric modulated arc therapy (VMAT) has also been introduced into clinical use. However, the IMRT dose delivery obtained by moving multileaf collimators was not consistent for a moving target.^7–10 By contrast, IMRT using compensated filter was capable of providing constant beams to a moving target and was consistent in the delivered dose distribution.^8,11,12 Furthermore, adjustment of respiratory-induced tumour motion is difficult^13,14 when multileaf collimators were used. We think gated irradiation using IMRT-compensated filter is an ideal method for moving targets. However, when using a compensator intensity modulation-based SBRT [non-coplanar IMRT (ncIMRT)] plan, the dosimetric benefit remains unknown for Stage I NSCLC. Thus, we investigated the benefits of the dose distribution of the ncIMRT plan for Stage I NSCLC via a comparison of the dosimetric parameters.     

Clinical-dosimetric relationship between lacrimal gland dose and ocular toxicity after intensity-modulated radiotherapy for sinonasal tumours

Objective:

To characterise the relationship between lacrimal gland dose and ocular toxicity among patients treated by intensity-modulated radiotherapy (IMRT) for sinonasal tumours.

Methods:

40 patients with cancers involving the nasal cavity and paranasal sinuses were treated with IMRT to a median dose of 66.0 Gy. Toxicity was scored using the Radiation Therapy Oncology Group morbidity criteria based on conjunctivitis, corneal ulceration and keratitis. The paired lacrimal glands were contoured as organs at risk, and the mean dose, maximum dose, V₁₀, V₂₀ and V₃₀ were determined. Statistical analysis was performed using logistic regression and the Akaike information criterion (AIC).

Results:

The maximum and mean dose to the ipsilateral lacrimal gland were 19.2 Gy (range, 1.4–75.4 Gy) and 14.5 Gy (range, 11.1–67.8 Gy), respectively. The mean V₁₀, V₂₀ and V₃₀ values were 50%, 25% and 17%, respectively. The incidence of acute and late Grade 3+ toxicities was 23% and 19%, respectively. Based on logistic regression and AIC, the maximum dose to the ipsilateral lacrimal gland was identified as a more significant predictor of acute toxicity (AIC, 53.89) and late toxicity (AIC, 32.94) than the mean dose (AIC, 56.13 and 33.83, respectively). The V₂₀ was identified as the most significant predictor of late toxicity (AIC, 26.81).

Conclusion:

A dose–response relationship between maximum dose to the lacrimal gland and ocular toxicity was established. Our data suggesting a threshold relationship may be useful in establishing dosimetric guidelines for IMRT planning that may decrease the risk of acute and late lacrimal toxicities in the future.

Advances in knowledge:

A threshold relationship between radiation dose to the lacrimal gland and ocular toxicity was demonstrated, which may aid in treatment planning and reducing the morbidity of radiotherapy for sinonasal tumours.The majority of tear fluid is produced by the paired lacrimal glands, which are located in the superior temporal quadrants of the orbits. Each bilobed lacrimal gland is anatomically divided into the larger orbital and smaller palpebral parts, both of which contain excretory components consisting of ductal cells that mechanically assist in the secretion of tears on to the ocular surface by modifying the fluid secreted by acinar and myoepithelial cells [1]. The glands of Krause and Wolfring are smaller accessory lacrimal glands located in the superior fornix that secrete additional tear fluid. Functionally, the lacrimal gland is responsible for the secretion of fluid that continually moistens, lubricates and protects the surface of the eye.An increasingly recognised complication of radiotherapy to the periorbital region is dry eye syndrome, defined by the International Dry Eye WorkShop as a “multi-factorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface accompanied by increased osmolarity of the tear film and inflammation of the ocular surface” [2]. Although previous research has suggested a variable association between radiation dose to the lacrimal gland and incidence of dry eye syndrome [3–11], the exact nature of this dose–response relationship remains undetermined. This is particularly relevant given the ability of intensity-modulated radiotherapy (IMRT) to limit dose to normal structures designated as organs at risk (OARs). The aim of the present study was to characterise this relationship between various dosimetric parameters related to the lacrimal gland and ocular toxicity in patients treated with IMRT for sinonasal tumours.     

MRI volumetry for prediction of tumour response to neoadjuvant chemotherapy followed by chemoradiotherapy in locally advanced rectal cancer

Objective:

To investigate if MRI-assessed tumour volumetry correlates with histological tumour response to neoadjuvant chemotherapy (NACT) and subsequent chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC).

Methods:

Data from 69 prospectively enrolled patients with LARC receiving NACT followed by CRT and radical surgery were analysed. Whole-tumour volumes were contoured in T₂ weighted MR images obtained pre-treatment (V_PRE), after NACT (V_NACT) and after the full course of NACT followed by CRT (V_CRT). V_PRE, V_NACT and tumour volume changes relative to V_PRE, ΔV_NACT and ΔV_CRT were calculated and correlated to histological tumour regression grade (TRG).

Results:

61% of good histological responders (TRG 1–2) to NACT followed by CRT were correctly predicted by combining V_PRE < 10.5 cm³, ΔV_NACT > −78.2% and V_NACT < 3.3 cm³. The highest accuracy was found for V_NACT, with 55.1% sensitivity given 100% specificity. The volume regression after completed NACT and CRT (V_CRT) was not significantly different between good and poor responders (TRG 1–2 vs TRG 3–5).

Conclusion:

MRI-assessed small tumour volumes after NACT correlated with good histological tumour response (TRG 1–2) to the completed course of NACT and CRT. Furthermore, by combining tumour volume measurements before, during and after NACT, more good responders were identified.

Advances in knowledge:

MRI volumetry may be a tool for early identification of good and poor responders to NACT followed by CRT and surgery in LARC in order to aid more individualized, multimodal treatment.Chemoradiotherapy (CRT) followed by complete surgical removal is regarded as a standard of care for patients diagnosed with locally advanced rectal cancer (LARC).¹ Therapeutic approaches incorporating additional agents to the standard fluorouracil (FU)-based CRT could potentially improve clinical outcome. Experimental studies have shown that intensified pre-operative treatment approaches with systemic neoadjuvant chemotherapy (NACT) before conventional long-course CRT have promising long-term outcome and acceptable safety profiles.^2–4 On the other hand, modern multimodal treatment based on MRI leads to excellent local control, but distant control remains a challenge.^5,6 Reliable identification of good and poor responders at an early stage could allow for more individualized, effective and less toxic treatment of these patients.Traditionally, image-based evaluation of treatment response has been performed by unidimensional measurements of tumour diameters.⁷ Volumetry may provide more accurate assessment, especially for irregular-shaped tumours, and the volumetric information can readily be obtained from standard high-resolution two-dimensional MR images. MRI volumetry is accepted as a sensitive predictive tool for assessment of treatment outcome after NACT and radiotherapy (RT) of cervical cancer.^8,9 In LARC, MRI-based tumour volume changes have been investigated as a parameter of treatment response after the full course of CRT.^10–14 Recognizing the dose–volume relationship,¹⁵ it is anticipated that small tumour volume at the time of CRT is correlated to good treatment response. To our knowledge, the potential of MRI volumetry after NACT alone has been explored only in two studies; a pilot study of 16 patients¹⁶ and a recent study of 40 patients;¹⁷ the latter also assessing the performance of fluorine-18 fludeoxyglucose positron emission tomography (¹⁸F-FDG-PET). By performing a third, independent and larger study, the reliability of MRI volumetry after NACT as a clinical tool is addressed.The main objective of the present study was to investigate if MRI-assessed tumour volumetry correlates with histological tumour response to NACT and subsequent CRT in LARC.     

Metabolic Tumor Volume Measured by F-18 FDG PET/CT can Further Stratify the Prognosis of Patients with Stage IV Non-Small Cell Lung Cancer

Purpose

This study aimed to further stratify prognostic factors in patients with stage IV non-small cell lung cancer (NSCLC) by measuring their metabolic tumor volume (MTV) using F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT).

Materials and Methods

The subjects of this retrospective study were 57 patients with stage IV NSCLC. MTV, total lesion glycolysis (TLG), and maximum standardized uptake value (SUVmax) were measured on F-18 FDG PET/CT in both the primary lung lesion as well as metastatic lesions in torso. Optimal cutoff values of PET parameters were measured by receiver operating characteristic (ROC) curve analysis. Kaplan-Meier survival curves were used for evaluation of progression-free survival (PFS). The univariate and multivariate Cox proportional hazards models were used to select the significant prognostic factors.

Results

Univariate analysis showed that both MTV and TLG of primary lung lesion (MTV-lung and TLG-lung) were significant factors for prediction of PFS (P < 0.001, P = 0.038, respectively). Patients showing lower values of MTV-lung and TLG-lung than the cutoff values had significantly longer mean PFS than those with higher values. Hazard ratios (95 % confidence interval) of MTV-lung and TLG-lung measured by univariate analysis were 6.4 (2.5–16.3) and 2.4 (1.0–5.5), respectively. Multivariate analysis revealed that MTV-lung was the only significant factor for prediction of prognosis. Hazard ratio was 13.5 (1.6–111.1, P = 0.016).

Conclusion

Patients with stage IV NSCLC could be further stratified into subgroups of significantly better and worse prognosis by MTV of primary lung lesion.     

Dosimetric effects of roll rotational setup errors on lung stereotactic ablative radiotherapy using volumetric modulated arc therapy

Objective:

To evaluate the dosimetric effects of roll-rotational setup errors of stereotactic ablative radiotherapy (SABR) for lung cancer using volumetric modulated arc therapy (VMAT).

Methods:

A total of 23 lung SABR cases were evaluated retrospectively. Each of the planning CT images was intentionally rotated by ±1°, ±2° and ±3°. After that, to simulate the translational couch correction, rotated CT images were moved along the x, y and z axis to match the centroid of the target volume in the rotated CT images with that in the original CT images. The differences in D_95% and V_100% of the target volume, D_0.35cc of spinal cord, D_0.35cc and D_5cc of oesophagus and V_20Gy of lung between the original and the rotated CT images were calculated.

Results:

The average differences in D_95% and V_100% of target volume, D_0.35cc of spinal cord, D_0.35cc and D_5cc of oesophagus and V_20Gy of lung were −0.3% ± 0.4% and −0.7% ± 2.4%, 1.6 ± 27.9 cGy, −1.6 ± 37.6 cGy, 15.9 ± 25.3 cGy and 0.0% ± 0.1%, respectively. The dosimetric changes in organs at risk (OARs) near the target volume were sometimes considerable due to roll-rotational setup errors, despite the translational correction, and those were patient specific.

Conclusion:

In the case of coplanar VMAT for lung SABR, dosimetric changes to the target volume due to roll-rotational setup errors could be compensated by translational correction, whereas those to the OARs could not in some cases.

Advances in knowledge:

Roll-rotational setup errors would increase the dose to OARs despite the translational correction.     

Predictors of late bowel toxicity using three different methods of contouring in patients undergoing post-operative radiation for cervical cancer

Objective:

This study investigates the correlation between dose–volume histogram derived from three bowel contouring methods and late toxicity in patients undergoing post-operative radiation therapy (PORT) for cervical cancer.

Methods:

From June 2010 to May 2013, 103 patients undergoing PORT were included. Three different contouring methods were used: (a) individual small bowel (SB) and large bowel (LB) loops, (b) total bowel (TB; including SB and LB) and (c) peritoneal cavity (PC). The volume of SB, LB, TB and PC receiving 15, 30 and 40 Gy was calculated. Acute and late bowel toxicities were scored using Common Terminology Criteria for Adverse events v. 3.0. Receiver operating characteristic curve identified thresholds predicting late toxicity with the highest specificity. All data were dichotomized across these thresholds. Univariate and multivariate analyses were performed using SPSS^® v. 20 (IBM Corporation, Armonk, NY; formerly SPSS Inc., Chicago, IL).

Results:

On univariate analysis, V₃₀ PC ≥ 900 cm³ (p = 0.01), V₄₀ PC ≥ 750 cm³ (p = 0.03) and V₄₀ TB ≥ 280 cm³ (p = 0.03) and use of concurrent chemotherapy (p = 0.03) predicted grade ≥II acute toxicity. On multivariate analysis, use of concurrent chemotherapy [odds ratio (OR) 3.5, 95% confidence interval (CI) 1.1–11.1, p = 0.03] and V₃₀ PC ≥ 900 cm³ (OR 2.3, 95% CI 1–5.5, p = 0.05) predicted acute grade ≥II toxicity. On univariate analysis for late toxicity, SB (V₃₀ ≥ 190 cm³, p = 0.009; V₄₀ ≥ 150 cm³, p = 0.03), LB (V₁₅ ≥ 250 cm³, p = 0.04), V₄₀ PC (V₄₀ ≥ 750 cm³, p = 0.001) and presence of acute grade ≥III toxicity (p = 0.006), treatment technique (three-dimensional conformal radiation or intensity modulated radiotherapy, p = 0.02) predicted more than or equal to grade ll late bowel toxicity. On multivariate analysis, only body mass index ≥25 kg m⁻² (OR 7.3, 95% CI 1.6–31.6, p = 0.008) and presence of acute grade III toxicity predicted toxicity (OR 5.1, 95% CI 1.4–18.1, p = 0.007).

Conclusion:

V₃₀ PC ≥ 900 cm³ and use of concurrent chemotherapy independently predicts acute toxicity. Presence of acute grade ≥III toxicity independently predicts late toxicity. Minimizing dose to PC subvolumes can therefore reduce both acute and late toxicities.

Advances in knowledge:

Study establishes PC thresholds that can minimize both acute and late bowel toxicities.     

Quantitative evaluation of background parenchymal enhancement (BPE) on breast MRI. A feasibility study with a semi-automatic and automatic software compared to observer-based scores

Objective:

To evaluate quantitative measurements of background parenchymal enhancement (BPE) on breast MRI and compare them with observer-based scores.

Methods:

BPE of 48 patients (mean age: 48 years; age range: 36–66 years) referred to 3.0-T breast MRI between 2012 and 2014 was evaluated independently and blindly to each other by two radiologists. BPE was estimated qualitatively with the standard Breast Imaging Reporting and Data System (BI-RADS) scale and quantitatively with a semi-automatic and an automatic software interface. To assess intrareader agreement, MRIs were re-read after a 4-month interval by the same two readers. The Pearson correlation coefficient (r) and the Bland–Altman method were used to compare the methods used to estimate BPE. p-value <0.05 was considered significant.

Results:

The mean value of BPE with the semi-automatic software evaluated by each reader was 14% (range: 2–79%) for Reader 1 and 16% (range: 1–61%) for Reader 2 (p > 0.05). Mean values of BPE percentages for the automatic software were 17.5 ± 13.1 (p > 0.05 vs semi-automatic). The automatic software was unable to produce BPE values for 2 of 48 (4%) patients. With BI-RADS, interreader and intrareader values were κ = 0.70 [95% confidence interval (CI) 0.49–0.91] and κ = 0.69 (95% CI 0.46–0.93), respectively. With semi-automated software, interreader and intrareader values were κ = 0.81 (95% CI 0.59–0.99) and κ = 0.85 (95% CI 0.43–0.99), respectively. BI-RADS scores correlated with the automatic (r = 0.55, p < 0.001) and semi-automatic scores (r = 0.60, p < 0.001). Automatic scores correlated with the semi-automatic scores (r = 0.77, p < 0.001). The mean percentage difference between automatic and semi-automatic scores was 3.5% (95% CI 1.5–5.2).

Conclusion:

BPE quantitative evaluation is feasible with both semi-automatic and automatic software and correlates with radiologists'' estimation.

Advances in knowledge:

Computerized BPE quantitative evaluation is feasible with both semi-automatic and automatic software. Computerized BPE quantitative scores correlate with radiologists'' estimation.