Upper limit of radiation treatment portals in rectal cancer: is it wise to keep using bony landmarks in the present era of 3D conformal treatment?

Background: This study aimed to compare the levels of L5-S1 interspace and the bifurcation of common iliac vessels on simulation images of rectal cancer patients to evaluate the adequacy of superior borders in conventional 2D planning for covering internal iliac vessels. Materials and methods: Simulation images of 236 rectal cancer patients who received neoadjuvant chemoradiation and surgery were analyzed. The images were retrieved from the radiation treatment database and included delineations of L5-S1 interspace and common iliac vessel bifurcation. Distances between these landmarks were measured. Results: Among the 236 patients, the majority had the common iliac artery bifurcation positioned above the L5-S1 interspace. Specifically, 78.3% of patients had the right common iliac bifurcation above L5-S1 interspace, with an average distance of 2.02 cm. For the left common iliac artery, 77.11% of patients had the bifurcation above L5-S1 interspace, with an average distance of 1.99 cm. Notably, there were cases where the bifurcations were not at the same level. Conclusion: Using the L5-S1 junction as the upper border of the treatment portal may result in missing proximal nodes at risk of metastases. However, further research is needed to determine the significance of failures above the L5-S1 interspace for justifying the inclusion of the common iliac artery bifurcation in the treatment portal.

Impact of nodal boost irradiation and MR-based brachytherapy on oncologic outcomes in node-positive cervical cancer.

This study aimed to prospectively evaluate the impact of dose-escalated irradiation of nodal metastases on clinical outcomes compared to no boost in patients with node-positive, bulky, locally advanced cervical cancer (LACC) undergoing standard chemoradiation and MRI-based brachytherapy. METHODS: This comparative study included 161 patients with node-positive LACC treated with definitive chemoradiation and MRI-based brachytherapy. The prospective Boost arm accrued 71 patients to receive nodal boost either sequentially or simultaneously to an equivalent dose of 60 Gy. The control arm comprised 90 patients treated before this protocol period with no additional nodal boost. RESULT: Baseline patient and tumor characteristics were similar in both groups. All patients had at least one tumor dimension >5 cm at presentation, and 31% had para-aortic node involvement. With a median follow-up of 36 months (IQR:19-50.5), the overall 3-year Local control rate was 88.8%. The 3-year Regional control (93% vs. 80%, p = 0.035) was statistically better in the Boost arm. No nodal failure was observed in nodes <3 cc and < 2 cm, even in the No-boost arm. There was no significant difference in Disease-free survival (67.6% vs. 58.9%,p = 0.454) and Overall Survival (78.9% vs. 74.4%,p = 0.87) between the two arms. Incidence of acute or late toxicities did not differ significantly with nodal boost or the boost delivery technique. CONCLUSION: The addition of external radiation nodal boost to standard treatment of high-volume cervical cancer has improved pelvic control with an acceptable rate of toxicities. However, high systemic failures continue to pose a challenge in improving survival outcomes.

Comparison of treatment response in cervical carcinoma patients infected with human papillomavirus 16 and human papillomavirus 18 who are treated with chemoradiation.

OBJECTIVES: The primary objective of this study was to compare the treatment response of cervical carcinoma patients infected with human papillomavirus (HPV) 16 and HPV 18 who are treated with chemoradiation. MATERIALS AND METHODS: Ninety-six biopsy-proven cervical cancer patients, suitable for curative treatment with definitive radio-chemotherapy with International Federation of Gynecology and Obstetrics Stage IB2-IIIB, were included in this prospective study. HPV testing was done using TRUPCR® HPV 16 and 18 real-time polymerase chain reaction kit. All the patients received a dose of 83-90 Gy total equieffective dose to the high risk clinical target volume(HRCTV) using tele- and brachytherapy. RESULTS: Of the 96 patients, 79 (82.3%) patients were positive for HPV DNA. Seventy-three patients showed HPV genotype 16 positivity and six patients were positive for genotype 18. The response was correlated with HPV genotype. There was a statistically significant increase in complete radiological response in HPV 16 compared to HPV 18 and negative groups at 3 months, 80.8%, 50%, and 52.9%, respectively (χ2 = 36.5, P < 0.001). There was also a statistically significant increase in clinical response at 3 months in HPV 16 group compared to HPV 18 and negative groups, 87.5%, 50%, and 50%, respectively (χ2 = 29.9, P < 0.001). The age, volume of the disease, overall treatment time, average hemoglobin level, and the number of blood transfusions did not have any correlation. CONCLUSION: HPV genotype 16 positivity shows higher complete response in cervical carcinoma patients treated with definitive chemoradiation compared to HPV 18 genotype. Further HPV genotyping could potentially help stratify cervical cancer patients for more effective therapeutic regimens.

Evaluation and evolution of apparent diffusion coefficient (ADC) in image-guided adaptive brachytherapy (IGABT) for cervical cancer.

PURPOSE: Image-guided adaptive brachytherapy (IGABT) recently has shown excellent clinical outcomes with superior local control and less toxicity. For IGABT, T2W (T2-weighted) MRI is the gold standard. However, studies have shown that target delineation with the same results in uncertainties, poor interobserver variabilities, and low conformity indices for high-risk clinical target volume contours. In this study, we investigate the role of diffusion-weighted imaging-derived apparent diffusion coefficient (ADC) maps to aid in IGABT. We also evaluated ADC from the baseline to brachytherapy. METHODS AND MATERIALS: Thirty selected patients were enrolled for this study, and two MRIs were taken at diagnosis and before brachytherapy. Patients were divided into two groups, Group 1 being patients with parametrial involvement before external beam radiotherapy and no parametrial involvement before brachytherapy. Group 2 included patients with parametrial involvement before external beam radiotherapy and persistent parametrial involvement before brachytherapy. ADC was measured at the center, edge, and 1 cm from the edge. RESULTS: The measured ADC increased from diagnosis to brachytherapy, and this increase was more for the patients in Group 1 than in Group 2. The mean TDadc (diagnosis ADC, center), TEadc (tumor edge ADC diagnosis), and T1cmDadc (1 cm from edge at diagnosis) were 0.884, 1.45, and 1.9 × 10-3 mm2/s, respectively. The TBadc (ADC at brachytherapy, center), TEBadc (tumor edge ADC at brachytherapy), and TE1cmBadc (1 cm from edge brachytherapy) were 1.2, 1.8, and 2.3 × 10-3 mm2/s, respectively, p-value <0.00001. No abnormal ADC was present outside the high-risk clinical target volume contours. CONCLUSION: MRI-based IGABT using T2W imaging essentially covers all functionally abnormal zones at brachytherapy. Diffusion-weighted imaging, along with ADC maps, should only be used as a supplement for target delineation.

A comparative study evaluating the dose volume parameters in 3D conformal radiation of left sided whole breast irradiation including regional lymphnodes - a need of resource constrained countries.

BACKGROUND: The purpose of this study was to compare four 3D conformal radiation techniques in treatment of left breast cancer patients. MATERIALS AND METHODS: Radiation was planned for 20 patients to the left breast and regional lymph nodes using four techniques: partially wide tangents, photon-photon mix, photon-electron mix and 30/70 photon-electron mix. All plans were evaluated for internal mammary nodes (IMN) coverage, hotspot and normal tissue constraints. RESULT: The 85% of planning target volume (PTV) coverage was lesser for upper IMN than the lower IMN (below the lower border of the clavicular head) for all four techniques. The lower IMN coverage was better for partially wide tangent (80.46%) and photon-photon mix (88.88%). The lowest value of hotspot was seen in the partially wide tangent technique (112.69% ± 1.92). Hotspot is unacceptably high in both photon-electron mix and 30/70 photon-electron mix (> 120%). Left lung mean dose for all techniques on a pair-wise comparison showed no statistical difference. Left lung V20 values for partially wide tangent was 37.56% ± 8.17 and for photon-photon mix it was 40.49% ± 3.36. The mean heart dose with partially wide tangent was 9.43 ± 3.15 Gy and with photon-photon mix it was 10.10 ± 2.70 Gy. The mean heart dose for photon-electron mix was 7.56 ± 1.95 Gy and for 30/70 photon-electron mix it was 7.98 ± 2.16 Gy. CONCLUSION: No single technique satisfies all the criteria. The decision should be made on a case-by-case basis, considering the anatomy of the patient, availability of electron facilities and setup accuracy and reproducibility.

A prospective comparative dosimetric study between diffusion weighted MRI (DWI) & T2-weighted MRI (T2W) for target delineation and planning in cervical cancer brachytherapy.

AIM: To evaluate the difference between GTVBT (Gross Tumor Volume at Brachytherapy) and HR CTV (High Risk Clinical Tumor Volume) delineated with DWI and T2W MRI. To evaluate doses to organs at risk and targets from plans generated using T2W and DWI. BACKGROUND: Functional imaging with DWI can improve cervical tumor distinction as it is more sensitive than T2W MRI even in detecting parametrial invasion. This study does a dosimetric comparison between a T2W and DWI based plan. METHODS: Fifty carcinoma cervix patients were subjected to MRI based brachytherapy. T2W and a diffusion weighted sequence were acquired. Target delineation and brachytherapy planning was done on both T2W and DWI. Standard DVH parameters were recorded and the treatment was given using the plan generated from T2W images. RESULTS: GTVBT and HRCTV contours on DWI were different when compared with T2W. Mean GTVBT volume on T2W and DWI was 5.25 and 5.23, respectively (p value 0.8). Mean HRCTV on T2W and DWI was 28.3 and 27 cc, respectively (p value 0.003). Planning on the above volumes resulted in a superior coverage in terms of HRCTV D90 and D100 for DWI based plan, HRCTV D90 - 735.1 and 741 cGy for T2W and DWI, respectively (p value 0.006), HRCTV D100 - 441.05 and 444.5 for T2W and DWI plans, respectively (p value = 0.006). Doses to the OAR were not significantly increased. CONCLUSION: GEC ESTRO based contouring guidelines cover all the functionally abnormal areas on DWI. DWI should only be used as a supplement to T2W for contouring target volumes.

Long-term effectiveness and safety of image-based, transperineal combined intracavitary and interstitial brachytherapy in treatment of locally advanced cervical cancer.

PURPOSE: The aim of the study was to evaluate the impact of image-based combined intracavitary-interstitial brachytherapy (IC-ISBT) using a transperineal template in locally advanced cervical cancer treatment. METHODS AND MATERIALS: A total of 94 patients of cervical cancer stage IIB-IVA underwent image-based transperineal interstitial brachytherapy without tandem (ISBT) or with tandem (IC-ISBT) between June 2008 and June 2018 at our institution. After pelvic chemoradiation, 42 patients underwent ISBT and 52 IC-ISBT. Dosimetric data, clinical response, and toxicity records of these patients were reviewed. RESULTS: Clinical stage distribution was as follows: IIB: 22.4% (21), IIIA: 10.6% (10), IIIB: 56.4% (53), and IVA: 10.6% (10). Mean high-risk clinical target volume was 75.72 cc, and mean cumulative equivalent of 2 Gy per fraction for high-risk clinical target volume was 81 Gy. The median followup was 35.5 months. Overall 3- and 5-year local control, disease-free survival (DFS), and overall survival (OS) were 84% and 84%, 69.1% and 62.9%, and 80.9% and 71.5%, respectively. Local control (90.4% vs. 76.2%; p = 0.048) and DFS (78.8% vs. 57.1%; p = 0.04) were significantly better in the patients of IC-ISBT arm. IC-ISBT (hazard ratio: 0.763; 95% confidence interval 0.217, 1.38; p = 0.046) and D90 dose >85 Gy (hazard ratio: 0.957; 95% confidence interval 0.927, 1.07; p = 0.037) were predictors of better DFS on univariate analysis. Overall survival was not affected significantly by any of the factors. Grade 3 and 4 late complications were recorded in 3.2% (3) of patients and were similar in both arms (p = 0.86). However, the mean rectum 2 cc dose was significantly lower in the IC-ISBT arm (p = 0.038). CONCLUSIONS: Combined IC-ISBT is a safe and effective approach to treat ICBT unsuitable cases. It integrates the benefits of ICBT to the adaptability of ISBT around various targets and should be practiced whenever feasible to provide superior outcomes in locally advanced cervical cancer.

Change of telomerase activity in peripheral blood of patients with head and neck squamous cell carcinoma pre and post curative treatment.

BACKGROUND: There is no clinically applicable tumor marker for head and neck cancers. Telomerase is detected in approximately 90% of all malignant tumors, it may predict poor or favorable outcomes, thus being both a highly attractive biomarker and a target for the development of molecular-based cancer diagnostics, prognostics, and therapeutics. AIM: Primary aim was to detect a change of telomerase activity before and after curative treatment. MATERIALS AND METHODS: Patients with biopsy proven head and neck squamous cell carcinoma, stage I-IVB treated with a curative intent, performance status 0-2 and malignancy at one primary site were included in the study. Telomerase levels were tested in tissue biopsy. Plasma telomerase levels were tested at baseline, 5 days and at 3 months after treatment using ELISA. RESULTS: Raised plasma telomerase activity was seen in all the patients with cancer at baseline. The mean plasma telomerase level at baseline was 861.4522 ng/ml, at 5 days after completion of curative treatment was 928.92 ng/ml and at 3 months of follow up was 898.87 ng/ml. The mean tissue biopsy telomerase level was 19768.53 ng/mg. There was a significant increase in baseline telomerase levels in cancer patients compared to normals (volunteers) (t = -3.52, p = 0.001).There was a significant increase in plasma levels of telomerase at 3 months compared to baseline values (z = -1.98, p = 0.04). The increase in telomerase level did not correlate with the response of the treatment. CONCLUSION: In patients with head and neck squamous cell carcinomas treated with a curative intent, the change in levels of telomerase correlates neither with the disease status nor with prognostic factors.

The promise of image-guided brachytherapy of better clinical outcomes in treatment of cervical cancer: Does it deliver? An Indian scenario.

PURPOSE: The purpose of this series is to study the effectiveness of MRI based image-guided brachytherapy (IGBT) in Indian patients with cervical cancer who mostly present in later stages with bulky diseases. PATIENTS AND METHODS: 151 cervical cancer patients treated at our institution in last four years, with definitive chemoradiation followed by MRI-based brachytherapy were reviewed. With median follow up of 26 months, Kaplan Meier estimates at two years were calculated for local control (LC), pelvic control (PC), disease-free survival (DFS) and overall survival (OS). Also, severe late sequelae were reported. RESULTS: The patients predominantly presented with locally advanced cervical cancer in FIGO stages IIB (53.6%) and IIIB (23.2%). Tumour dimensions at diagnosis were ≥5 cm in 56.3% and pelvic nodal involvement was found in 38.4% of the patients. 94% of the patients received curative chemoradiation. Mean HRCTV volume at the time of brachytherapy was 42.2 ±â€¯19 cm3 and mean cumulative dose to HRCTV was 78.9 ±â€¯5.6 Gy. Overall LC, PC, DFS and OS at 2 years were 88.7%, 88.1%, 82.2% and 94% respectively. The predictors for local failure were FIGO stage (p = 0.002) and tumour size at diagnosis (p = 0.009). Late grade 3-4 bladder and bowel toxicities were observed in 3.8% of the patients. CONCLUSION: Our review demonstrates that IGBT is an effective strategy to improve locoregional control with limited long-term sequelae in patients with locally advanced extensive cervical cancer in the setting of a developing country.

Study of distribution of inguinal nodes around the femoral vessels and contouring of inguinal nodes.

AIMS: To determine the distribution of inguinal nodes around the vessels, margins needed around the vessels and inferior extent of contouring in the inguinal region. SUBJECTS AND METHODS: Fifty patients having pelvic malignancies with one or more malignant nodes in the inguinal region were retrospectively included in this study. The position of the nodes in relation to the vessels, size of the nodes, the distance from the center of the node to the edge of the nearest vessel was measured. Margins required to cover the nodes from the vessels and position of the nodes in relation to the lesser trochanter was noted. RESULTS: Most of the nodes were placed either anteromedial (46%) or anterior (46.6%) to the vessels (92.6%). The range of margin required to cover all nodes in the anteromedial, anterior and anteriolateral direction varied from 0.8 to 2.7 cm. Only one node was more than 2 cm below the lower edge of lesser trochanter. CONCLUSION: Elective clinical target volume for inguinal lymph nodes requires a minimum margin of 2.5 cm from the femoral vessels in the anterior, anterolateral and anteromedial direction 1.5 cm margin is required medially. Inferior extent of the contour should be 2 cm below the lower edge of lesser trochanter.

Carcinoma cervix presenting with clivus metastasis.

We present an unusual case of a large metastatic lesion from carcinoma cervix located in the clivus. Patient presented with severe headache and vomiting, mimicking an intracranial pathology. Radiological imaging suggested metastatic origin of the lesion and later on investigations revealed primary in the uterine cervix. The anatomic importance of extradural neural axis component in the process of metastasis of carcinoma cervix to the clivus is highlighted in this case report.

Unusual metastatic presentation of carcinoma hypopharynx.

Cutaneous metastases from hypopharyngeal cancers is rare constituting about 0.8-1.3% and represent a sub-group of head and neck cancer patients who have very poor prognosis even when treated. We report a case of 65-year-old male diagnosed as carcinoma hypo pharynx stage IV who was on radiotherapy when he developed cutaneous metastasis over the chest wall, which initially presented as small nodules and later progressed into a proliferative lesion. Patient received further radiation to the metastatic lesion, but the disease was progressive, demonstrating that head and neck squamous cell cancer patients with skin metastasis fare poorly.

A rare case of cisplatin-induced acute myocardial infarction in a patient receiving chemoradiation for lung cancer.

We present this unusual case of cisplatin-induced acute myocardial infarction in a patient with no organic coronary artery disease (CAD), receiving chemoradiation for small cell lung cancer. Patient developed symptoms of acute coronary syndrome after receiving two cycles of cisplatin and etoposide. The possible mechanism of vasospasm induced by cisplatin, in the background of thoracic radiation and hypomagnesemia, is discussed in this case report.