Is Thoracic Radiotherapy an Absolute Contraindication for Treatment of Lung Cancer Patients With Interstitial Lung Disease? A Systematic Review.

Thoracic radiotherapy decisions in patients with interstitial lung disease (ILD) are complex due to concerns about severe or even fatal radiation pneumonitis. This systematic review analysed the published evidence regarding the incidence of radiation pneumonitis and mortality after thoracic radiotherapy and investigated clinical and dosimetric predictors of radiation pneumonitis in lung cancer patients with ILD. A systematic search was carried out in PubMed, Medline, Embase and the Cochrane database for articles published between January 2000 and April 2021. Two authors independently screened eligible studies that met our predefined criteria. Studies were assessed for design and quality and a qualitative data synthesis was carried out. The search strategy resulted in 1750 articles. After two rounds of screening, 24 publications were included. The median overall incidence of grade ≥3 radiation pneumonitis was 19.7% (range 8-46%). The incidence was greater in conventional radical radiotherapy-treated patients (median 31.8%) compared with particle beam therapy- or stereotactic ablative radiotherapy-treated patients (median 12.5%). The median rate of grade 5 radiation pneumonitis was 11.9% (range 0-60%). The presence of ILD was an independent predictor of severe radiation pneumonitis. Severe radiation pneumonitis was more common in the presence of usual interstitial pneumonia (UIP) pattern or idiopathic pulmonary fibrosis (IPF) than non-UIP or non-IPF subtype. Several other clinical predictors were reported in the literature. V5, V10, V20 and mean lung dose were the most common dosimetric predictors for severe radiation pneumonitis, often with stricter dose constraints than conventionally used. Patients with lung cancer associated with ILD had a poorer overall survival compared with patients without ILD. In conclusion, patients with lung cancer associated with ILD have a poor prognosis. They are at high risk of severe and even fatal radiation pneumonitis. Careful patient selection is necessary, appropriate high-risk consenting and strict lung dose-volume constraints should be used, if these patients are to be treated with thoracic radiotherapy.

Continuous hyperfractionated accelerated radiotherapy using modern radiotherapy techniques for nonsmall cell lung cancer patients unsuitable for chemoradiation.

INTRODUCTION: The continuous hyperfractionated and accelerated radiotherapy (CHART) regimen of radiotherapy (RT) for nonsmall cell lung cancer is underused outside the UK. We present the first Indian experience of using CHART for patients, who were not suitable for chemotherapy or concurrent chemo-RT. METHODS: We retrospectively reviewed the data of patients treated using CHART at our institution between January 2014 and December 2015. RESULTS: Thirty-seven patients were treated using CHART. Planning methods and dosimetry parameters are described. Three-dimensional conformal RT was used for treatment planning and delivery in 23 patients and volumetric modulated arc RT was necessary for 14 patients. Patients in our series had a median age of 70 years (interquartile range 65.50-74.00) and 86.5% had Stage III disease. Median follow-up was short at 13.0 months. Actuarial rates of 1-year progression-free survival, 1-year overall survival (OS), and 2-year OS were 31.9%, 59.5%, and 28.5%, respectively. This treatment was well tolerated with manageable and some reversible acute esophageal toxicity (91.9% CONCLUSION: Our results indicate that CHART is feasible, safe, and well tolerated in Indian patients who are clinically found to be not suitable for either sequential or concurrent chemo- RT.

Actual gains in dosimetry and treatment delivery efficiency from volumetric modulated arc radiotherapy for inoperable, locally advanced lung cancer over five-field forward-planned intensity-modulated radiotherapy.

AIMS: Volumetric modulated arc radiotherapy (VMAT) is used for inoperable, locally advanced nonsmall cell lung cancer, where three-dimensional conformal radiotherapy (3D-CRT) cannot yield an acceptable plan. METHODS: The planning and treatment data were prospectively collected on the first 18 patients treated using VMAT plans. We analyzed the actual dosimetric gain and impact on treatment, compared with complex multisegment 3D-CRT (five-field forward-planned intensity-modulated radiotherapy [IMRT]) that were generated for treatment. Proportion of planning target volume (PTV) receiving 95% dose (PTV-V95%) conformity index (CI), conformity number (CN), dose homogeneity index (DHI), monitor units (MUs), and treatment time were also analyzed. RESULTS: The PTV coverage (PTV-V95%) was improved from a median of 91.41% for 5-F forward-IMRT to 98.25% for VMAT (P < 0.001). The CI improved with a mean of 1.12 for VMAT and 1.31 for 5-F forward-IMRT (P < 0.001). The mean DHI improved from 1.15 for forward-IMRT to 1.08 for VMAT (P < 0.001). The mean CN improved from 0.62 for forward-IMRT to 0.87 for VMAT (P < 0.001). No significant increase in the low-dose bath (V5, V10 and mean lung dose) to the lung was seen. Significantly higher number of MUs (P < 0.001) and shorter treatment delivery times (P = 0.03) were seen with VMAT. CONCLUSION: VMAT resulted in improvement in target volume coverage, demonstrated by PTV-V95%, CI, CN, and DHI, without any increase in the low-dose bath to the lung. For conventional fractionation, VMAT requires more MUs (P < 0.001) but has a shorter treatment delivery time (P = 0.03) per fraction.

High-dose Neural Stem Cell Radiation May Not Improve Survival in Glioblastoma.

AIMS: To evaluate the effect of radiotherapy dose-volume parameters of neural stem cell (NSC) compartment on progression-free survival (PFS) and overall survival after post-resection chemoradiation in newly diagnosed glioblastoma. MATERIALS AND METHODS: Sixty-one patients with unifocal glioblastoma were included. Ipsilateral (NSC_Ipsi), contralateral (NSC_Contra) and combined NSC (NSC_Combined) were contoured on radiotherapy planning computerised tomography datasets. NSC dose-volume parameters were correlated with PFS and overall survival. Serial magnetic resonance imaging scans were assessed to understand the frequency of pre- and post-treatment involvement of the NSC by contrast enhancing lesions (CELs). RESULTS: Baseline involvement of NSC with CELs was seen in 67.2% and 95.9% had CELs and FLAIR abnormalities at progression. With a median follow-up of 14.1 months (interquartile range 9.4-20.6 months), median PFS and overall survival were 14.5 (95% confidence interval 11.6-17.5) and 16.2 (95% confidence interval 13.3-19.2) months, respectively. Poor Eastern Cooperative Oncology Group performance score, advanced recursive partitioning analysis class, unmethylated O6-methylguanine methyltransferase (MGMT) status, higher than median of mean NSC_Ipsi dose were associated with significantly inferior PFS and overall survival on univariate analysis. On multivariate analysis, unmethylated MGMT status, higher than median of mean doses to NSC_Ipsi and poor compliance to adjuvant temozolomide were independent predictors of inferior survival. CONCLUSIONS: In this cohort, 67.2% of newly diagnosed glioblastoma patients had NSC involved with CELs at presentation and 95.9% at progression. This might be an imaging surrogate of the current notion of gliomagenesis and progression from NSC rests. A high radiation dose to NSC_Ipsi was significantly associated with inferior survival. This could be a function of larger tumours and planning target volumes in those with pre-treatment NSC involvement. Methylated MGMT and good compliance to adjuvant temozolomide were independent predictors of better survival. Until further evidence brings hope for glioblastoma, elective, partial NSC irradiation remains experimental.

Outcomes Following a Moderately Hypofractionated Adjuvant Radiation (START B Type) Schedule for Breast Cancer in an Unscreened Non-Caucasian Population.

AIMS: Breast cancer is the most common cancer in women. Western data have confirmed hypofractionated radiation therapy to be safe and effective in the adjuvant radiation therapy of breast cancers. We report the disease-related outcomes in a non-Caucasian, unscreened population treated with hypofractionated radiation. MATERIALS AND METHODS: Unselected case notes of patients presenting to a tertiary cancer centre between June 2011 and December 2013 were reviewed from the electronic hospital case records. Patients with a diagnosis of non-metastatic invasive non-sarcomatous breast cancer were identified. Demographic information, oestrogen receptor (ER), progesterone receptor (PR), HER2 status, pathological tumour, nodal stage at diagnosis and outcomes of treatment, including systemic therapies, surgery and hypofractionated radiation, were documented. Local recurrence rates, disease-free survival (DFS) and overall survival were calculated. RESULTS: Overall 925 patents were identified, median age 53.0 years (interquartile range 45-61), 330 of whom had neoadjuvant chemotherapy. The median follow-up time was 22.6 months and 23.5 months for overall and neoadjuvant chemotherapy groups, respectively. ER, PR and HER2 status was available in 788 patients, 77.2% of whom were ER/PR positive, 14.7% had triple negative disease, while 9.5% were HER2 rich. Overall, 34.2% (113 patients) underwent breast conservation surgery; 744 (80.4%) patients were treated with systemic chemotherapy and 878 (94.9%) patients received adjuvant radiation therapy, of whom 407 (44.0%) received supraclavicular-fossa radiotherapy. Overall survival, DFS and locoregional recurrence-free survival (LRRFS) for the overall group were 93%, 86.9% and 97.1%, respectively. LRRFS in the breast conservation surgery versus mastectomy groups were 99% versus 95.5% (P=0.003), with more node-positive patients in the mastectomy group. Stage N0/1 had better LRRFS compared with N2/2 (99.1% versus 95.7%); 94.3% versus 82.3%; P=0.005, 0.000. Grade 3 (53.8%) tumours had worse overall survival compared with grade 1 or grade 2 disease (89.6% versus 100% and 96.4%; P<0.001) although the LRRFS was not significantly different between the groups (98.9% versus 97.8%; P=0.37). There was no difference in LRRFS based on molecular subtypes. CONCLUSION: Local recurrence rates following hypofractionated radiation in our population were comparable with those reported by the START trialists and were found to be safe in the medium term for patients irrespective of breast conservation surgery/mastectomy or radiotherapy to the supraclavicular field. Molecular group frequencies were comparable with Western populations but did not affect LRRFS.

Evaluating the Need for Daily Image Guidance in Head and Neck Cancers Treated with Helical Tomotherapy: A Retrospective Analysis of a Large Number of Daily Imaging-based Corrections.

AIMS: Clinical implementation of image-guided intensity-modulated radiotherapy is rapidly evolving. Helical tomotherapy treatment delivery involves daily imaging before intensity-modulated radiotherapy delivery. This can be a time consuming resource-intensive process, which may not be essential in head and neck radiotherapy, where effective immobilisation is possible. This study aimed to evaluate whether an offline protocol implementing the shifts derived from the first few fractions can be an acceptable alternative to daily imaging for helical tomotherapy. MATERIALS AND METHODS: We retrospectively analysed the set-up data of 2858 fractions of 100 head and neck cancer patients who were treated with daily online image guidance. Using summary data from all treatment fractions, we calculated the systematic error (∑) and random error (σ) in each of the three axes, i.e. mediolateral (x), craniocaudal (y), anteroposterior (z). We also calculated the translational vector of each fraction of individual patients. We then simulated two no-action-level offline protocols where set-up errors of the first three (protocol F3) or five fractions (protocol F5) were averaged and implemented for the remaining fractions. The residual errors in each axis for these fractions were determined together with the residual ∑ and σ. Planning target volume (PTV) margins using the van Herk formula were generated based on the uncorrected errors as well as for the F3 and F5 protocols. For each scenario, we tabulated the number of fractions where the residual errors were more than 5 mm (our default PTV margin). We also tried to evaluate whether errors tended to differ based on intent (radical or adjuvant), anatomical subsite or weight loss during treatment. RESULTS: Analysis from this large dataset revealed that in the tomotherapy platform, the highest set-up errors were in the anteroposterior (z) axis. The global mean was 5.4 mm posterior shift, which can be partly attributed to couch sag on this system. Uncorrected set-up errors resulted in systematic and random errors of ∑x,y,z of 1.8, 1.7 and 2 mm and σx,y,z of 1.7, 1.5 and 1.9 mm, with a required PTV margin in x, y, z axes of 5.7, 5.3 and 6.2 mm. Implementing average shifts from the first three or five fractions resulted in a substantial reduction in the residual systematic errors, whereas random errors remained constant. The PTV margins required for the residual errors after three and five fraction corrections were 3.8, 3.4 and 5.1 mm for F3 and 3.3, 2.9, 4.8 mm for F5. The proportions of fractions where there was >5 mm residual error were 1.6%, 1.1%, 2.9% in x, y and z axes in the F3 protocol and 1.5%, 0.8% and 2.6% with the F5 protocol. Although there was no difference in residual shifts > 5 mm, there was a statistically higher chance of residual errors > 3 mm larynx/hypopharynx subsites versus other sites. In patients who had more than 5% weight loss, there was no significant increase in residual errors with the F5 protocol and the required PTV margin was within our default PTV margins expansion. CONCLUSIONS: Correction of systematic errors by implementing average shifts from the first five fractions enables us to safely avoid daily imaging in this retrospective analysis. If this is validated in a prospective group it could lead to implementation of a resource sparing image-guided radiotherapy protocol both in terms of time and imaging dose. Patients with larynx/hypopharynx subsites may require more careful evaluation and daily online matching.

Pitfalls and Challenges to Consider before Setting up a Lung Cancer Intensity-modulated Radiotherapy Service: A Review of the Reported Clinical Experience.

Intensity-modulated radiotherapy (IMRT) is being increasingly used for the treatment of non-small cell lung cancer (NSCLC), despite the absence of published randomised controlled trials. Planning studies and retrospective series have shown a decrease in known predictors of lung toxicity (V20 and mean lung dose) and the maximum spinal cord dose. Potential dosimetric advantages, accessibility of technology, a desire to escalate dose or a need to meet normal organ dose constraints are some of the factors recognised as supporting the use of IMRT. However, IMRT may not be appropriate for all patients being treated with radical radiotherapy. Unique problems with using IMRT for NSCLC include organ and tumour motion because of breathing and the potential toxicity from low doses of radiotherapy to larger amounts of lung tissue. Caution should be exercised as there is a paucity of prospective data regarding the efficacy and safety of IMRT in lung cancer when compared with three-dimensional conformal radiotherapy and IMRT data from other cancer sites should not be extrapolated. This review looks at the use of IMRT in NSCLC, addresses the challenges and highlights the potential benefits of using this complex radiotherapy technique.

Low-dose palliative splenic irradiation in haematolymphoid malignancy.

Patients are treated with palliative splenic irradiation (SI) to relieve pain, volume effects and the clinical consequences of hypersplenism. The case records of 19 patients treated with palliative SI at our centre, from April 2003 to November 2004, were reviewed. Twenty-two courses of SI were identified. The radiation doses delivered ranged from 150 to 800 cGy (median 450 cGy). The fraction sizes ranged from 25 to 100 cGy. Parallel-opposed anteroposterior-posteroanterior portals were the most common field arrangement. The target volume was reduced in 18 out of 22 courses. The percentage of field reduction ranged from 0 to 59.57% (mean 24.82%). Twelve of 14 courses were successful in achieving symptom palliation. Of the six patients who received SI for a combination of splenic symptoms and abnormal blood tests, five had symptomatic palliation but only one patient responded haematologically. Of two patients who were started on palliative SI for abnormal haematology alone, only one responded. In summary, 17 of 20 (85%) courses of SI initiated for symptom control resulted in effective palliation. Only two of eight (25%) courses of SI started for abnormal blood counts produced a desired response. To conclude, SI offers an effective and well-tolerated palliative treatment option.

Integrins and disintegrins: the candidate molecular players in sperm-egg interaction.

Fertilization includes sperm-egg recognition, adhesion, binding, fusion and egg activation. Integrin (ITG) receptors which are adhesion molecules are expressed on mouse, hamster and human gametes and their potential ligands also have been identified. Role of ITGs during fertilization is supported by inhibition of sperm-egg adhesion and/or fusion by means of anti-ITG mAbs, Arg-Gly-Asp (RGD) or disintegrin-like peptides. This review includes the current understanding of the molecular mechanism that regulates sperm-egg interaction and implications of this knowledge for assessing the fertility potential of men and immunocontraceptive method.