Biological tailoring of adjuvant radiotherapy in head and neck and oral malignancies - The potential role of p53 and eIF4E as predictive parameters.

BACKGROUND: Recent advances in radiation technology has allowed to significantly reduce toxicity and improve the efficacy of radical radiotherapy in head and neck and oral squamous cell cancers. Insights into molecular biology of carcinogenesis has opened a window for identifying aggressive clinical situations that may benefit with larger clinical target volume (CTV ) margin, broader levels of nodal coverage, or alternative radiation sensitizers. AIM: To evaluate the potential role of eukaryotic translation initiation factor 4E (elF4E) and p53 as predictive biomarkers in resected margins of head and neck and oral cancers. MATERIAL AND METHODS: Forty patients with oral cancers and 26 patients with head and neck cancers were evaluated for p53 and eIF4E in their negative surgical margins, for pattern of distribution and outcome. RESULTS: In oral cancers, 27 patients (67.5%) were positive for p53 and 10 (25%) for eIF4E in surgically negative margins. For head and neck cancer, the values were 13 (50%) for p53 and 9 (34.6%) for eIF4E. Twelve patients with oral cancers and 8 patients with head and neck cancers had local failure or death. The association with these biomarkers did not achieve statistical significance. However, adjuvant radiotherapy had a significant protective value. It improved median survival from 15 to 21 months in patients positive for p53 (P = 0.018) and from 12 to 20 months (P = 0.03) in those with eIF4E. There was no predictive association of subsite, tumor size, or nodal status. CONCLUSION: The overexpression of p53 and eIF4E in pathologically negative margins may represent a subset of patients who would benefit from early initiation of adjuvant radiation and tailored intensity-modulated radiotherapy (IMRT).

Breast-conserving radiotherapy with simultaneous integrated boost; field-in-field three-dimensional conformal radiotherapy versus inverse intensity-modulated radiotherapy - A dosimetric comparison: Do we need intensity-modulated radiotherapy?

BACKGROUND AND PURPOSE: To examine the feasibility of improving breast-conserving radiotherapy with simultaneous integrated boost (SIB) and analyzing the efficiency of forward versus inverse intensity-modulated radiotherapy (IMRT) techniques in providing the same. MATERIALS AND METHODS: Three-dimensional conformal radiotherapy (3DCRT) field-in-field (FIF) plans with simultaneous and sequential boost and IMRT SIB plans were generated for the datasets of 20 patients who had undergone breast-conserving surgery. The 3 plans were compared dosimetrically for efficiency in terms of planning target volume (PTV) coverage (PTV 95%), homogeneity and conformity, dose delivered to ipsilateral/contralateral lungs (I/L: V10, V20, C/L: Vmean, V5), heart and contralateral breast (Vmean, V30 for heart and Vmean, V1, V5 for C/L breast). RESULTS: The FIF 3DCRT plan with SIB (PLAN B) was more homogeneous than the classical technique with sequential boost (PLAN A). There were less hot spots in terms of Dmax (63.7 ± 1.3) versus Dmax (68.9 ± 1), P < 0.001 and boost V107%, B (0.3 ± 0.7) versus A (3.5 ± 5.99), P = 0.001. The IMRT SIB (PLAN C) did not provide any significant dosimetric advantage over the 3DCRT SIB technique. IMRT SIB plan C was associated with increased dose to contralateral lung in-terms of V5 (10.35 +/- 18.23) vs. (1.13 +/- 4.24), P = 0.04 and Vmean (2.12 ± 2.18) versus Vmean (0.595 ± 0.89), P = 0.008. There was 3-fold greater exposure in terms of Monitor Unit (MU) (1024.9 ± 298.32 versus 281.05 ± 20.23, P < 0.001) and treatment delivery time. CONCLUSIONS: FIF 3DCRT SIB provides a dosimetrically acceptable and technically feasible alternative to the classical 3DCRT plan with sequential boost for breast-conserving radiotherapy. It reduces treatment time by 2 weeks. IMRT SIB does not appear to have any dosimetric advantage; it is associated with significantly higher doses to contralateral lung and heart and radiation exposure in terms of MU.

Nimotuzumab provides survival benefit to patients with inoperable advanced squamous cell carcinoma of the head and neck: a randomized, open-label, phase IIb, 5-year study in Indian patients.

OBJECTIVE: Overexpression of epidermal growth factor receptor (EGFR) in many cancers makes it an attractive therapeutic target. This study evaluated the clinical utility of nimotuzumab, a monoclonal anti-EGFR antibody, used concurrently with radiotherapy (RT) and chemoradiotherapy (CRT) in squamous cell carcinoma of the head and neck (SCCHN). METHODS: This open-label study randomized 92 treatment-naïve patients (1:1) with advanced SCCHN into chemoradiation (CRT ± nimotuzumab) or radiation (RT ± nimotuzumab) group by investigator's discretion; these were further randomized into CRT + nimotuzumab or CRT and RT + nimotuzumab or RT groups, respectively. Treatment included 6 cycles each of cisplatin (50 mg/week), nimotuzumab (200 mg/week), and RT (total dose, 60-66 Gy). Response (tumor size reduction) was assessed at Month 6 post-treatment and survival, at Month 60. RESULTS: Forty and 36 patients in the chemoradiation and radiation groups, respectively (intent-to-treat population) were evaluated. Overall response at Month 6 post-treatment was 100% with CRT + nimotuzumab, 70% with CRT, 76% with RT + nimotuzumab, and 37% with RT. At Month 60, overall survival was 57% with CRT + nimotuzumab, 26% with CRT (P = 0.03), 39% with RT + nimotuzumab, and 26% with RT (P > 0.05). Median overall survival was not reached for CRT + nimotuzumab; it was 21.94 months for CRT (P = 0.0078), 14.36 months for RT + nimotuzumab, and 12.78 months for RT (P = 0.45). Risk of death was 64% lower with CRT + nimotuzumab than with CRT (95%CI: 0.37, 1.56), and 24% lower with RT + nimotuzumab than with RT (95%CI: 0.16, 0.79). Thus nimotuzumab was safe and well tolerated with few mild to moderate self-limiting adverse events. CONCLUSION: Concurrent use of nimotuzumab with CRT/RT is safe and provides long-term survival benefit.

Radiosensitization in head and neck cancer: do we have an alternative to platins? Role of taxanes.

In the past few decades, concurrent chemoradiation has conclusively been established as the standard of care in resectable, locally advanced head and neck cancer. Platins until now have been the established radiosensitizer in all concurrent settings, including postoperative high-risk scenarios. However, retrospective and evolving data suggest that they have their limitations in terms of compatibility, toxicity, and intrinsic resistance. There is therefore the need to explore the scope of other agents that may address these issues through a different mode of action, a better toxicity profile, or preferably a combination of both. In recent years, taxanes have emerged as an effective chemotherapeutic agent for head and neck cancer for recurrent or metastatic disease and chemoinduction for downstaging before definitive treatment. In this article, the authors review the potential of taxanes as an alternative to platins in the concurrent setting.

Cyberknife: A double edged sword?

The Cyberknife represents a new, frameless stereotactic radiosurgery system which efficiently incorporates advance robotics with computerized image reconstruction to allow highly conformal image guided radiation delivery. This review focus is on the pros and cons of this new radiotherapy tool, its current indications, safety profile and future directions. A literature search of Medline, Pubmed, Biomed, Medscape and Cancer lit database were referred to retrieve relevant data/information. The authors conclude that the use of this system offers an invaluable solution to the treatment of selective tumours/lesions located close to critical structures, salvage of recurrent and metastatic lesions and potential of treatment of selective early stage malignancies like the carcinoma prostate and lung. However, it is still too premature, with insufficient follow up data to advocate it as the treatment of choice in any set up. There are several radiobiological issues that also remain in the greyzone.

Mixed exocrine-endocrine pancreatic carcinoma in childhood.

A 7-year-old boy with mixed exocrine-endocrine pancreatic cancer is presented. This may be the second reported case of such a tumor in childhood.