The value of intratumoral heterogeneity of 18F-FDG uptake to differentiate between primary benign and malignant musculoskeletal tumours on PET/CT

Objective:

The cumulative standardized uptake value (SUV)–volume histogram (CSH) was reported to be a novel way to characterize heterogeneity in intratumoral tracer uptake. This study investigated the value of fluorine-18 fludeoxyglucose (¹⁸F-FDG) intratumoral heterogeneity in comparison with SUV to discriminate between primary benign and malignant musculoskeletal (MS) tumours.

Methods:

The subjects comprised 85 pathologically proven MS tumours. The area under the curve of CSH (AUC-CSH) was used as a heterogeneity index, with lower values corresponding with increased heterogeneity. As 22 tumours were indiscernible on ¹⁸F-FDG positron emission tomography, maximum standardized uptake value (SUV_max), mean standardized uptake value (SUV_mean) and AUC-CSH were obtained in 63 positive tumours. The Mann–Whitney U test and receiver operating characteristic (ROC) analysis were used for analyses.

Results:

The difference between benign (n = 35) and malignant tumours (n = 28) was significant in AUC-CSH (p = 0.004), but not in SUV_max (p = 0.168) and SUV_mean (p = 0.879). The sensitivity, specificity and accuracy for diagnosing malignancy were 61%, 66% and 64% for SUV_max (optical threshold value, >6.9), 54%, 60% and 57% for SUV_mean (optical threshold value, >3) and 61%, 86% and 75% for AUC-CSH (optical threshold value, ≤0.42), respectively. The area under the ROC curve was significantly higher in AUC-CSH (0.71) than SUV_max (0.60) (p = 0.018) and SUV_mean (0.51) (p = 0.005).

Conclusion:

The heterogeneity index, AUC-CSH, has a higher diagnostic accuracy than SUV analysis in differentiating between primary benign and malignant MS tumours, although it is not sufficiently high enough to obviate histological analysis.

Advances in knowledge:

AUC-CSH can assess the heterogeneity of ¹⁸F-FDG uptake in primary benign and malignant MS tumours, with significantly greater heterogeneity associated with malignant MS tumours. AUC-CSH is more diagnostically accurate than SUV analysis in differentiating between benign and malignant MS tumours.     

Acute effects of pelvic irradiation on the adult uterus revealed by dynamic contrast-enhanced MRI

Objective:

Pelvic radiation therapy (RT) can influence fertility in female rectal cancer survivors. Data regarding its effects on the adult uterus are scant. This study aims to evaluate the uterus before and after RT, using dynamic contrast-enhanced MRI.

Methods:

Eligible patients (n=10) received RT for rectal cancer, had an intact uterus and underwent dynamic contrast-enhanced MRI before and after RT. Seven patients were pre-menopausal.

Results:

Patients received pelvic RT (median, 50.2 Gy) with concurrent 5-fluorouracil. Five patients were treated with intensity modulated RT (IMRT) and five with a three-field technique. The median D95 of the uterus was 30 Gy; D05 was 48 Gy; and V95 was 97%. The median cervical D95 was 45 Gy; D05, 50 Gy; and V95, 100%. Cervical dose was higher with IMRT than with three-field plans (p≤0.038). On T₂ MRI, the junctional zone was visible in nine patients before and in one after RT (p=0.001). Median cervical length (2.3 vs 3.0 cm) and endometrial thickness (2.6 vs 5.9 mm) were reduced after RT (p≤0.008). In pre-menopausal patients, the volume transfer constant, K_trans, (0.069 vs 0.195, p=0.006) and the extracellular extravascular volume fraction, V_e, (0.217 vs 0.520, p=0.053) decreased.

Conclusion:

Pelvic RT significantly affected uterine anatomy and perfusion. Cervical dose was higher with IMRT than three-field plans, but no attempt was made to constrain the dose.

Advances in knowledge:

Pelvic RT significantly affects the adult uterus. These findings are crucial to understand the potential consequences of RT on fertility, and they lay the groundwork for further prospective studies.As the cure rate in locally advanced rectal cancer continues to improve, understanding the long-term sequelae of therapy is gaining importance. Research has shown that young cancer survivors are concerned about treatment-related effects on fertility, pregnancy and neonatal outcomes [1,2]. Previously, pelvic irradiation, standard in the management of locally advanced rectal cancer, invariably caused sterility in females as a result of acute ovarian failure. Currently, however, the risk of ovarian dysfunction may be greatly reduced by transposing the ovaries to the paracolic gutters before radiation therapy (RT) [3]. Additionally, an increasing number of females undergo embryo or oocyte cryopreservation before receiving RT [4]. These advances prompt the question: if a young female has undergone pelvic RT, can she carry a pregnancy to term?Answering this question requires an understanding of the effects of the pelvic RT on the uterus. Ultrasounds of paediatric cancer survivors suggest that pelvic RT alters uterine volume, distensibility and vasculature, with patients who are younger at the time of RT being the most vulnerable to these effects [5–7]. Additionally, population-based studies of paediatric cancer survivors have demonstrated an association between abdominal and/or pelvic RT and adverse pregnancy and neonatal outcomes, including placental abnormalities, pre-term delivery, low birth weight infants and perinatal mortality [8–11]. However, only sparse data exist regarding the effects of pelvic RT on the adult uterus, which may be more radioresistant.The aim of this study was to use dynamic contrast-enhanced (DCE) MRI to assess the acute effects of RT on the uterus in females treated for locally advanced rectal cancer. A second aim was to compare dosimetric parameters of conventional three-field RT and intensity modulated RT (IMRT) treatment plans.     

Acute anal toxicity after whole pelvic radiotherapy in patients with asymptomatic haemorrhoids: identification of dosimetric and patient factors

Objective:

Patients with asymptomatic haemorrhoids are known to be less tolerant of radiation doses lower than known tolerance doses. In the present study, the authors sought to identify the risk factors of acute haemorrhoid aggravation after whole pelvic radiotherapy (WPRT).

Methods:

The records of 33 patients with cervical, rectal or prostate cancer with asymptomatic haemorrhoids, which were confirmed by colonoscopy before the start of radiotherapy (RT), were reviewed. Acute anal symptoms, such as anal pain and bleeding, were observed up to 1 month after RT completion. Dosimetric and patient factors were analysed, and subgroup analyses were performed.

Results:

The median induction dose for acute anal symptoms was 34.1 Gy (range, 28.8–50.4 Gy). Post-operative treatment intent showed more acute anal toxicity of patient factors (p = 0.04). In subgroup analysis, post-operative treatment intent and concurrent chemoradiotherapy were found to be related to acute anal symptoms (p < 0.01). Of the dosimetric factors, V₁₀ tended to be related to acute anal symptoms (p = 0.08).

Conclusion:

This study indicates that asymptomatic haemorrhoid may deteriorate after low-dose radiation and that patient factors, such as treatment intent and concurrent chemotherapy, probably influence anal toxicity. In patients with asymptomatic haemorrhoids, WPRT requires careful dosimetry and clinical attention.

Advances in knowledge:

The tolerance of anal canal tends to be ignored in patients with pelvic cancer who are undergoing WPRT. However, patients with asymptomatic haemorrhoids may be troubled by low radiation doses, and further studies are required.Radiotherapy (RT) is widely used for cancer treatment along with surgery and chemotherapy.^1–5 In particular, whole pelvic RT (WPRT) plays an important role in the locoregional control of pelvic lesions in cervical, rectal and prostate cancer. Although RT is an effective anticancer treatment, it can induce complications in normal organs. There are a lot of studies about radiation tolerance doses in normal organs.^6–8Intestinal problems are common complications of WPRT, whereas severe complications, such as small bowel perforation, are rare.^9,10 On the other hand, acute anal complications, such as anal pain or bleeding, tend to be ignored because of their lower severities. However, acute anal toxicity is a painful, intractable complication. Although most acute anal problems improve spontaneously after RT completion, they are difficult to resolve during RT and result in complaints from many patients. WPRT is usually administered at doses ≤50 Gy, that is, at doses generally considered safe for the anal canal,¹¹ but when patients have haemorrhoids, RT-induced anal toxicity may become problematic.Haemorrhoids are very common and the incidence of asymptomatic haemorrhoids is high.¹² If a patient has haemorrhoids before RT, in many institutions, an anal block is used empirically. Most clinicians expect anal toxicity in patients with haemorrhoids following RT, but published studies on the topic are rare.In the present study, we sought to identify the risk factors of acute anal toxicity following WPRT in patients with pelvic cancer with asymptomatic haemorrhoids.     

0-7-21 hypofractionated palliative radiotherapy: an effective treatment for advanced head and neck cancers

Objective:

We report our experience in providing palliative radiotherapy (RT) to patients with head and neck cancers (HNCs). Our hypofractionated regimen, “0-7-21”, treats patients with 24 Gy in three fractions.

Methods:

Patients, disease and response data were retrieved for candidates of 0-7-21 from 2005 to 2012. Primary end points included symptom and tumour size responses to RT based on response evaluation criteria in solid tumours (RECIST) guidelines. Secondary end points included progression-free survival (PFS) within the irradiated field, overall survival (OS) and symptomatic PFS (SPFS), calculated using Kaplan–Meier method and adverse events. Cox proportional hazards regression and logistic regression were used to investigate for prognostic factors.

Results:

A total of 110 patients were included. Among the patients, 40% and 31% had complete response for symptoms and tumour size, respectively; 42% and 50% had partial response for symptoms and tumour size, respectively; and 15% had stability of symptoms and tumour size. Median 6-month OS was 51%, and PFS within the irradiated field was 39%. Planning target volume was predictive of OS (p < 0.001), PFS (p < 0.001) and SPFS (p < 0.005), while higher TNM stage was associated with poorer tumour response (p = 0.02).

Conclusion:

0-7-21 is an effective and well-tolerated palliative RT regimen for patients with HNC. There was excellent symptom and local control with acceptable toxicity profile in these patients.

Advances in knowledge:

This is the first study to describe the outcomes of 0-7-21 in treating advanced HNCs. The positive results suggest that 0-7-21 provides excellent palliation with minimal toxicity, with significantly less on-treatment time than current published palliative RT regimen.Head and neck cancer (HNC) is the sixth most common solid malignancy,¹ and the seventh leading cause of cancer death worldwide.² Up to 70% of patients present with locally advanced disease where cure is difficult to achieve.³ In these cases, palliative radiotherapy (RT) is often necessary, as these patients are highly symptomatic from their disease situated at critical locations in the upper aerodigestive tract.Currently, there is no consensus or guideline for palliative RT for patients with locally advanced HNC, unlike other clinical situations such as for patients with metastatic disease to the bone or brain or even for advanced lung cancer.^4–6 There are few retrospective reviews of the diverse schedules of palliative RT in advanced HNC. However, most of these studies use palliative therapy as a synonym for failed radical therapy. Although longer courses with higher total RT doses have been associated with marginally better outcomes in retrospective reviews,^7,8 patients not amenable to curative treatments continue to have a dismal prognosis with a median survival of 3–12 months, even with protracted treatments.^3,7,9,10 Furthermore, delivering an extended course of RT often constitutes a challenge given the poor performance status of these patients. Therefore, the question arose as to whether a shorter course of RT with a high biological effective dose would be more appropriate, assuming it offered satisfactory symptom and disease control.In our institution at the Juravinski Cancer Centre, a palliative hypofractionated RT regimen, termed “0-7-21”, is often proposed to patients with advanced incurable and unresectable HNC, especially those with poor performance status and/or multiple comorbidities or evidence of distant metastatic disease. This treatment course consists of three fractions of 8 Gy, given over 3 weeks for a total of 24 Gy. We undertook a retrospective study of our experience, analysing the efficacy of 0-7-21.     

Stereotactic body radiation therapy for a new lung cancer arising after pneumonectomy: dosimetric evaluation and pulmonary toxicity

Objective:

To evaluate the tolerance of stereotactic body radiation therapy (SBRT) for the treatment of secondary lung tumours in patients who underwent previous pneumonectomy.

Methods:

12 patients were retrospectively analysed. The median maximum tumour diameter was 2.1 cm (1–4.5 cm). The median planning target volume was 20.7 cm³ (2.4–101.2 cm³). Five patients were treated with a single fraction of 26 Gy and seven patients with fractionated schemes (3 × 10 Gy, 4 × 10 Gy, 4 × 12 Gy). Lung toxicity, correlated with volume (V) of lung receiving >5, >10 and >20 Gy, local control and survival rate were assessed. Median follow-up was 28 months.

Results:

None of the patients experienced pulmonary toxicity > grade 2 at the median dosimetric lung parameters of V₅, V₁₀ and V₂₀ of 23.1% (range 10.7–56.7%), 7.3% (2.2–27.2%) and 2.7% (0.7–10.9%), respectively. No patients required oxygen or had deterioration of the performance status during follow-up if not as a result of clinical progression of disease. The local control probability at 2 years was 64.5%, and the overall survival at 2 years was 80%.

Conclusion:

SBRT appears to be a safe and effective modality for treating patients with a second lung tumour after pneumonectomy.

Advances in knowledge:

Our results and similar literature results show that when keeping V₅, V₁₀ V₂₀ <50%, <20% and <7%, respectively, the risk of significant lung toxicity is acceptable. Our experience also shows that biologically effective dose 10 >100 Gy, necessary for high local control rate, can be reached while complying with the dose constraints for most patients.     

Stereotactic body radiotherapy for adrenal oligometastasis in lung cancer patients

Objective:To report our experience on stereotactic body radiotherapy (SBRT) in adrenal metastases from lung cancer.Methods:37 oligometastatic lung cancer patients with 38 adrenal metastases submitted to SBRT were retrospectively analyzed. SBRT was delivered by volumetric modulated arc therapy (VMAT) or helical tomotherapy (HT). Primary study end point was local recurrence-free survival (LR-FS) and secondary end points were distant-progression free survival (d-PFS) and overall survival (OS).Results:Median age was 67 years and primary tumor was non-small-cell lung cancer in 27 (73%) and small-cell lung cancer in 10 (27%) patients. Adrenal metastases were in the left side in 66% cases. Median prescribed dose was 30 Gy in 5 fractions for a median biologically equivalent dose (α/β ratio 10  Gy, BED10) of 48 Gy. Most patients (62%) were submitted to SBRT alone, while the others (38%) received chemo-, immune- or target- therapies. Median follow-up was 10.5 months, median OS 16 months and median d-PFS 3 months. 27 (70%) patients obtained a local control with a median LR-FS of 32 months. LR-FS was significantly related to BED10 with a better LC with BED10 ≥72 Gy, 1- and 2 year LR-FS rates were 54.1±11.6% and 45±12.7% vs 100 and 100% for BED ≤59.5 Gy and BED ≥72 Gy, respectively (p = 0.05). There was no severe toxicity.Conclusion:SBRT was effective and safe in lung cancer adrenal metastases. A dose–response relationship was found between BED10 >72 Gy and better local control. No significant toxicity was registered thanks to the respect of dose constraints and suspension of chemo- and target-therapies.Advances in knowledge:SBRT with a BED10 >72 Gy is an effective treatment for adrenal oligometastatic lung cancer patients.     

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.     

Pattern of lymph node metastases and its implication in radiotherapeutic clinical target volume in patients with non-small-cell lung cancer: a study of 2062 cases

Objective:

To study the pattern of lymph node metastasis (LNM) of non-small-cell lung cancer (NSCLC) and to clarify which node level should be included while undergoing radiotherapy (RT).

Methods:

A total of 2062 patients with NSCLC patients who had undergone thoracotomy were retrospectively examined. The clinicopathological factors related to LNM were analysed.

Results:

The LNM rates (the number of node-positive patients/the total number of patients) in patients with primary tumours in different lobes (left upper lobe, left lower lobe, right upper lobe, right middle lobe and right lower lobe) were 53.25%, 53.87%, 53.77%, 64.67% and 61.58%, respectively. We have found that in all of the clinicopathological factors, including sex, age, tumour location, histological type, maximum diameter, T stage, degree of differentiation and tumour growth pattern, only maximum diameter (p = 0.336) and histological type (p = 0.360) did not have significant correlation with LNM rate. All of the above factors except tumour growth pattern (p = 0.239) and maximum diameter (p = 0.613) were significantly associated with lymph node ratio [LNR, ratio between metastatic and examined lymph nodes (LNs)] in linear regression.

Conclusion:

For patients with NSCLC, LNM rate and LNR can be recommended as applicable parameters for LN involvement. Multiple clinicopathological factors should be considered comprehensively to design the clinical target volume for RT of NSCLC.

Advances in knowledge:

This article can provide evidence to radio-oncologists how to choose range of lymph nodal clinical target volume when they are treating inoperable patients with NSCLC patients by analysing data of patients after surgery.     

Evaluation of lung cancer by enhanced dual-energy CT: association between three-dimensional iodine concentration and tumour differentiation

Objective:

To investigate the correlation between iodine concentration of dual-energy CT (DECT) and histopathology of surgically resected primary lung cancers.

Methods:

We reviewed the medical records, post-operative pathological records and pre-operative DECT images of patients who underwent surgical lung resection for primary lung cancer. After injection of iodinated contrast media, arterial and delayed phases were scanned using 140- and 80-kV tube voltages. Three-dimensional iodine concentration (iodine volume) of primary tumours was calculated using lung nodule application software.

Results:

A total of 60 patients (37 males and 23 females; age range, 39–84 years; mean age, 69 years) with 62 lung cancers were analysed. The resected tumours were histopathologically classified into well-differentiated (G1; n = 20), moderately differentiated (G2; n = 29), poorly differentiated (G3; n = 9) and undifferentiated (G4; n = 4) groups by degree of tumour differentiation (DTD). The mean ± standard deviation of iodine volume at the delayed phase was 59.6 ± 18.6 HU in G1 tumours, 46.5 ± 11.3 HU in G2 tumours, 34.3 ± 15.0 HU in G3 tumours and 28.8 ± 6.4 HU in G4 tumours; significant differences were observed between groups (p < 0.001). Univariate logistic regression analysis showed that iodine volumes both at the early and delayed phases were significantly correlated with DTD (p = 0.006 and p = 0.001, respectively), whereas gender, body weight and tumour size were not (p = 0.084, p = 0.062 and p = 0.391, respectively).

Conclusion:

The iodine volume of lung cancers was significantly associated with their DTD. High-grade tumours tended to have lower iodine volumes than low-grade tumours.

Advances in knowledge:

Iodine volume measured by DECT could be a valuable functional imaging method to estimate differentiation of primary lung cancer.     

Semi-quantitative contrast-enhanced MR analysis of indeterminate ovarian tumours: when to say malignancy?

Objective:

To evaluate the ability of dynamic post-contrast sequence to specify indeterminate ovarian masses with inconclusive MR features of malignancy. Since management is dramatically different, special focus on the ability to differentiate borderline from invasive malignancy was considered.

Methods:

150 ovarian masses were detected by pelvic ultrasound in 124 patients. Masses had been considered for dynamic post-contrast MRI. We expressed the kinetic parameters (i.e. enhancement amplitude, time peak of maximal uptake and maximal slope) in the form of maximum relative enhancement percentage (MRE%), time of maximal peak of contrast uptake (T_max) and slope enhancement ratio (SER) curves. Histological findings were the gold standard of reference.

Results:

Malignant ovarian masses showed higher MRE% than benign and borderline masses (p < 0.001). T_max was shorter for malignant than benign (p < 0.01) and borderline (p < 0.001) ovarian masses. SER curves were the most suggestive of malignancy with a specificity and accuracy of 85.7% and 84.7%, respectively.

Conclusion:

Dynamic contrast-enhanced MRI could be a specific sequence to differentiate ovarian masses with indeterminate MR morphology with a special discrimination for low potential from invasive ovarian malignancy.

Advances in knowledge:

The study evaluated the diagnostic performance of the individual parameters of dynamic post-contrast MR sequence in evaluating ovarian masses. Management divert between benign, borderline and invasive malignant masses; our work presented a cut-off value for the peak of contrast uptake of 120%, which helped in the differentiation between benign and malignant tumours; the SER curves with Type III (early washout) pattern that was indicative of invasive malignancy was more specific than borderline malignancy.     

Differentiation of benign and malignant lesions of the tongue by using diffusion-weighted MRI at 3.0?T

Objectives:

Diffusion-weighted MRI (DWI) has been introduced in head and neck lesions and adds important information to the findings obtained through conventional MRI. The purpose of this study was to assess the role of DWI in differentiating benign and malignant lesions of the tongue at 3.0-T field strength imaging.

Methods:

78 patients with 78 lingual lesions underwent conventional MRI and DWI with b-values of 0 and 1000 s mm⁻² before therapy. The apparent diffusion coefficient (ADC) maps were reconstructed, and the ADC values of the lingual lesions were calculated and compared between benign and malignant lesions of the tongue.

Results:

The mean ADC values of the malignant tumours, benign solid lesions and cystic lesions were (1.08 ± 0.16) × 10⁻³, (1.68 ± 0.33) × 10⁻³ and (2.21 ± 0.35) × 10⁻³ mm² s⁻¹, respectively. The mean ADC values of malignant tumours were significantly lower (p < 0.001) than those of benign solid lesions, and the mean ADC values of benign solid lesions were significantly lower (p < 0.001) than those of cystic lesions. Receiver operating characteristic analysis showed that when an ADC value <1.31 × 10⁻³ mm² s⁻¹ was used for predicting malignancy, the highest accuracy of 95.3%, sensitivity of 92.6% and specificity of 97.3% were obtained.

Conclusions:

ADC values of benign and malignant lesions are significantly different at 3.0-T imaging. DWI can be applied as a complementary tool in the differentiation of benign and malignant lesions of the tongue.     

Split-course accelerated hyperfractionated irradiation (CHA-CHA) as a sole treatment for advanced head and neck cancer patients—final results of a randomized clinical trial

Objective:

Evaluation of the efficacy and toxicity of split-course accelerated hyperfractionated irradiation (CHA-CHA) as a sole treatment for advanced head and neck (H&N) cancer patients.

Methods:

We enrolled 101 patients (39 in CHA-CHA and 37 in conventional (Conv.) arm completed the treatment). The CHA-CHA arm patients were irradiated twice a day, 7 days a week, using a fraction dose (fd) of 1.6 Gy up to 64 Gy with an 8-day gap in midterm. Patients in the control (Conv.) arm group were irradiated with a fd of 2 Gy, five times a week to a total dose of 72–74 Gy in the overall treatment time of 50–53 days. Quality of life (QOL) and acute mucosal reaction were evaluated during radiotherapy (RT). After RT, we followed the effect of treatment, QOL, performance status and adverse effects of radiation. For statistical analysis mainly a hierarchical multilevel modelling was used.

Results:

QOL was most deteriorated in the CHA-CHA arm; the CHA-CHA scheme also caused a relatively stronger acute injury. There were no significant differences in late adverse effects. In the CHA-CHA arm in 35% and in Conv. arm in 30% of patients, disease was controlled during follow-up. Tumour regression 1 year after the treatment was significantly better in the CHA-CHA arm. However, the overall survival rate analysis did not show significant difference between both arms.

Conclusion:

Despite differences in treatment results, we cannot conclude that split-course accelerated hyperfractionated irradiation is superior to conventionally fractionated RT as a sole treatment for advanced H&N cancer patients.

Advances in knowledge:

Obtained results in the context of published data support the statement that altered fractionations alone do not give an advantage for advanced H&N cancer patients.There are, and have been, many attempts to create a clear and effective treatment modality for advanced inoperable head and neck (H&N) cancers. The most common are different combinations of chemoradiotherapy, or different schedules of altered and usually intensive radiation treatment. It is clear that intense dose delivery combined with a high total dose (TD) and short treatment time gives a higher probability of tumour destruction; unfortunately, it is also connected with a higher, usually unacceptable, risk of normal tissue damage. One of the causes of radiation toxicity in such cases is the inability of sufficient repair of healthy tissue damage.The reason for this is the intensity of dose delivery and the lack of time for repopulation of normal cells and proper repair. On the other hand, the accelerated repopulation of squamous cancer cells starts 4 weeks after radiotherapy (RT); therefore, radiation treatment should be completed in that time. Considering the aforementioned facts, we tried to construct a very intense and short RT schedule allowing for normal tissue (mainly mucosa) repair. We went back to the old concept of split-course RT and combined it with accelerated, continuous, intense hyperfractionation.Finally, we proposed twice-a-day irradiation, using fraction doses of 1.6 Gy, 7 days a week up to a TD of 32 Gy, an 8-day gap and the repetition of such course. Using this schedule, the treatment was completed exactly within 4 weeks to avoid repopulation of accelerated tumour clonogens and the 8-day gap in the midterm allowed for normal tissue repair.     

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.     

Tree-based exploration of the optimization objectives for automatic cervical cancer IMRT treatment planning

Objective:To develop and evaluate a practical automatic treatment planning method for intensity-modulated radiation therapy (IMRT) in cervical cancer cases.Methods:A novel algorithm named as Optimization Objectives Tree Search Algorithm (OOTSA) was proposed to emulate the planning optimization process and achieve a progressively improving IMRT plan, based on the Eclipse Scripting Application Programming Interface (ESAPI). 30 previously treated cervical cancer cases were selected from the clinical database and comparison was made between the OOTSA-generated plans and clinical treated plans and RapidPlan-based (RP) plans.Results:In clinical evaluation, compared with plan scores of the clinical plans and the RP plans, 22 and 26 of the OOTSA plans were considered as clinically improved in terms of plan quality, respectively. The average conformity index (CI) for the PTV in the OOTSA plans was 0.86 ± 0.01 (mean ± 1 standard deviation), better than those in the RP plans (0.83 ± 0.02) and the clinical plans (0.71 ± 0.11). Compared with the clinical plans, the mean doses of femoral head, rectum, spinal cord and right kidney in the OOTSA plans were reduced by 2.34 ± 2.87 Gy, 1.67 ± 2.10 Gy, 4.12 ± 6.44 Gy and 1.15 ± 2.67 Gy. Compared with the RP plans, the mean doses of femoral head, spinal cord, right kidney and small intestine in the OOTSA plans were reduced by 3.31 ± 1.55 Gy, 4.25 ± 3.69 Gy, 1.54 ± 2.23 Gy and 3.33 ± 1.91 Gy, respectively. In the OOTSA plans, the mean dose of bladder was slightly increased, with 2.33 ± 2.55 Gy (versus clinical plans) and 1.37 ± 1.74 Gy (vs RP plans). The average elapsed time of OOTSA and clinical planning were 59.2 ± 3.47 min and 76.53 ± 5.19 min.Conclusion:The plans created by OOTSA have been shown marginally better than the manual plans, especially in preserving OARs. In addition, the time of automatic treatment planning has shown a reduction compared to a manual planning process, and the variation of plan quality was greatly reduced. Although improvement on the algorithm is warranted, this proof-of-concept study has demonstrated that the proposed approach can be a practical solution for automatic planning.Advances in knowledge:The proposed method is novel in the emulation strategy of the physicists’ iterative operation during the planning process. Based on the existing optimizers, this method can be a simple yet effective solution for automated IMRT treatment planning.     

Randomised clinical trial on 7-days-a-week postoperative radiotherapy vs. concurrent postoperative radio-chemotherapy in locally advanced cancer of the oral cavity/oropharynx

Objective:To compare the efficacy and tolerance of 7-days-a-week accelerated postoperative radiotherapy (p-CAIR) vs postoperative radio-chemotherapy (p-RTCT)Methods:Between September 2007 and October 2013, 111 patients were enrolled and randomly assigned to receive 63 Gy in 1.8 Gy fractions 7-days-a-week (n = 57, p-CAIR) or 63 Gy in 1.8 Gy fractions 5-days-a-week with concurrent cisplatin 80–100 mg per square meter of body-surface area on days 1, 22 and 43 of the radiotherapy course (p-RTCT). It represents approximately 40% of the intended trial size, that was closed prematurely due to slowing accrual. Only high-risk patients with squamous cell cancer of the oropharynx/oral cavity, considered fit for concurrent treatment were enrolled.Results:The rate of locoregional control (LRC) did not differ significantly between treatment arms (p = 0.18, HR = 0.56), 5 year LRC tended, however, to favour p-RTCT (81%) vs p-CAIR (62%). There was no difference in overall survival between treatment arms (p = 0.90, HR = 1.03).The incidence and severity of acute mucosal reactions and late reactions did not differ significantly between treatment arms. Haematological toxicity of p-RTCT was, however, considerably increased compared to p-CAIRConclusion:Concurrent postoperative RTCT tended to improve locoregional control rate as compared to p-CAIR. This, however, did not transferred into improved overall survival. Postoperative RTCT was associated with a substantial increase in haematological toxicity that negatively affected treatment compliance in this arm.Advances in knowledge:To our knowledge, this is the first trial that compares accelerated radiotherapy and radio-chemotherapy in postoperative treatment for oralcavity/oropharyngeal cancer     

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.     

Consequences of additional use of contrast-enhanced 18F-FDG PET/CT in target volume delineation and dose distribution for pancreatic cancer

Objective:

To compare the differences between contrast-enhanced (CE) fluorine-18 fludeoxyglucose (¹⁸F-FDG) positron emission tomography (PET)/CT and CECT in target volume delineation and radiotherapy (RT) dose distribution, and to evaluate the sparing of organs at risk (OARs) in the treatment plan of locally advanced pancreatic cancer (LAPC).

Methods:

21 consecutive patients with LAPC with histologically or cytologically confirmed adenocarcinoma underwent both non-CECT and ¹⁸F-FDG scans; 11 of whom also underwent CECT scans. Intensity-modulated RT plans (prescribed dose, 54 Gy) were constructed to cover the corresponding gross tumour volume (GTV). The differences among GTV_CT, GTV_PET, GTV_PET-CT and OARs in these different image sets as well as the uniformity of target dose were analysed.

Results:

The mean non-CE GTV_CT, GTV_PET and GTV_PET-CT were 76.9 ± 47.8, 47.0 ± 40.2 and 44.5 ± 34.7 cm³ (mean ± standard deviation), respectively. The non-CE GTV_PET-CT was significantly smaller than the non-CE GTV_CT (p < 0.001). The CE GTV_PET-CT was significantly smaller than the CE GTV_CT (p = 0.033). For both the non-CE GTV_CT and the CE GTV_CT, the intestine V₄₀ (the percentage of the intestine volume irradiated by 40 Gy), intestine V₅₀, intestine D_max (the mean maximum dose), cord D_max, left kidney V₃₀, right kidney V₃₀, left kidney D_mean (the mean dose), right kidney D_mean and liver V₃₀ were 5.90%, 2.52%, 5500 cGy, 2194 cGy, 3.40%, 0.68%, 747 cGy, 550 cGy and 5.37%, respectively. There are significant differences between the non-CE CT and the non-CE PET-CT in intestine D_max (p = 0.023) and right kidney D_mean (p = 0.029).

Conclusion:

Co-registration of ¹⁸F-FDG PET with CECT may improve the accuracy of GTV delineation in LAPC and might reduce the adverse effect of irradiation.

Advances in knowledge:

Individual adaptation of RT based on functional CE ¹⁸F-FDG PET/CT imaging is possible and highly promising in LAPC.Pancreatic cancer (PC) is the fourth most common cause of cancer death in the USA with 5-year overall survival (OS) rates of <5%.¹ PC is a notoriously insidious disease, and about 70% of patients newly diagnosed with this malignancy are not amenable to curative surgery.² Concurrent chemoradiotherapy is the main treatment for locally advanced or recurrent PC, and radiotherapy (RT) plays a key role for local control. There are still many unresolved issues related to the delineation of the gross tumour volume (GTV) in locally advanced PC (LAPC), such as the difficulty in distinguishing the vasculature from tumour parenchyma, defining the tumour boundary on contrast-enhanced CT (CECT) in the absence of functional positron emission tomography (PET) imaging, and the presence of adjoining organs at risk (OARs), such as the small intestine, spinal cord, kidney and liver. The delineation of the GTV based on PET-CT fusion images could improve RT planning by reducing the target volume and the exposure volumes of the respective OARs and safely escalating the target radiation dose. Conventional enhanced CT scanning could not identify the extent of local tumour and lymph node invasion from peripheral structures precisely,³ which may result in inaccurate target delineation.Our study aimed to explore the value of the CE fluorine-18 fludeoxyglucose (¹⁸F-FDG) PET-CT fusion images for target volume delineation, dose distribution in OARs and the uniformity of target dose compared with the results of CT scan-based plans in LAPC.     

Differential Findings of Tc-99m Sestamibi Dual-Phase Parathyroid Scintigraphy Between Benign and Malignant Parathyroid Lesions in Patients with Primary Hyperparathyroidism

Purpose

This study aimed to investigate the differential findings in clinical and biochemical features, and Tc-99m sestamibi (MIBI) dual-phase parathyroid scintigraphy for malignant and benign parathyroid lesions in patients with primary hyperparathyroidism.

Methods

Subjects were 102 parathyroid lesions from 91 patients with primary hyperparathyroidism. Scintigraphic findings included radioactivity grade, uptake pattern, uptake contour, lesion size on early and delayed images, and degree of washout. Clinical and biochemical features were also evaluated. Histopathology confirmed the final diagnosis for all the patients.

Results

Final diagnoses were 94 benign parathyroid lesions and 8 parathyroid carcinomas. The patients with parathyroid carcinoma were significantly older (p = 0.002) and had significantly higher serum parathyroid hormone concentrations than those with benign parathyroid lesions (p < 0.001). All malignant parathyroid lesions showed intense radioactivity similar to or greater than the submandibular gland activity on delayed images (p = 0.007), and little radioactivity difference between early and delayed images (p = 0.012). The cancer incidence for parathyroid lesions with both intense radioactivity and no washout was 17.0% (8/47). When parathyroid lesions with all of the above-mentioned findings were regarded as malignant, the cancer incidence significantly increased from 17.0% to 33.3% (8/24, p < 0.001).

Conclusion

For Tc-99m MIBI dual-phase parathyroid scintigraphy, uptake grade on delayed images and washout were significantly useful diagnostic criteria for differentiating benign from malignant parathyroid lesions, along with age and parathyroid hormone serum concentration.