Specific growth rates calculated from CTs in patients with head and neck squamous cell carcinoma: a retrospective study performed in Austria.

OBJECTIVE: To provide data on specific growth rates (SGRs) of primary tumours (PT-SGR) and largest pathological cervical lymph nodes (LN-SGR) for head and neck squamous cell carcinoma (HNSCC). To explore PT-SGR's and LN-SGR's correlation with selected biomarkers epidermal growth factor receptor (EGFR), Ki67 and CD44. DESIGN AND SETTING: Retrospective study performed at a tertiary oncological referral centre in Innsbruck, Austria. PARTICIPANTS: Adult patients with incident HNSCC treated with primary radiotherapy (RT) or radiochemotherapy (RCT). OUTCOME MEASURES: Volumes of the primary tumour (PT-volume) and largest pathological cervical lymph node (LN-volume) were measured in CT scans obtained at time of diagnosis and subsequent planning CTs immediately prior to RT or RCT. SGRs were calculated assuming an exponential growth function. PT-SGR's and LN-SGR's correlation with EGFR, Ki67 and CD44 were explored. RESULTS: In 123 patients, mean interval between diagnostic and planning CT was 29±21 days. PT-SGR was 1.8±1.8% (mean±SD) per day and was positively correlated with EGFR, Ki67 and CD44 expression (p=0.02; p=0.02; p=0.03). LN-SGR was 1.7±2.0% per day and increased with larger initial LN-volume, was lower in laryngeal cancer (p=0.003) and slowed down with time. LN-SGR was not correlated with EGFR, Ki67 or CD44 expression in primary tumours (p>0.12). New cartilage or bone infiltration occurred in 10 patients and new central lymph node necrosis in 8 patients. CONCLUSIONS: HNSCCs are fast-growing tumours for which treatment must not be delayed. Clinical tumour growth rates are influences by EGFR, KI67 and CD44 expression.

Persistent Head and Neck Cancer Following First-Line Treatment.

Background: Following first-line treatment of head and neck cancer (HNC), persistent disease may require second-line treatment. Methods: All patients with HNC treated between 2008 and 2016 were included. Second-line treatment modalities and survival of patients were analyzed. Results: After first-line therapy, 175/741 patients had persistent disease. Of these, 112 were considered eligible for second-line treatment. Second-line treatment resulted in 50% complete response. Median overall survival of patients receiving second-line therapy was 24 (95% CI: 19 to 29) months; otherwise survival was 10 (9 to 11; p < 0.0001) months. Patients receiving second-line surgery had a median overall survival of 45 (28 to 62) months, patients receiving second-line radiotherapy had a median overall survival of 37 (0 to 79; p = 0.17) months, and patients receiving systemic therapy had a median overall survival of 13 (10 to 16; p < 0.001) months. Patients with persistent HNC in the neck had a better median survival (45 months; 16 to 74 months; p = 0.001) than patients with persistence at other sites. Conclusion: Early treatment response evaluation allows early initiation of second-line treatment and offers selected patients with persistent disease a realistic chance to achieve complete response after all. If possible, surgery or radiotherapy are preferable.

Prognostic value of tumor volume in patients with head and neck squamous cell carcinoma treated with primary surgery.

BACKGROUND: Tumor volume in head and neck squamous cell carcinoma (HNSCC) was mainly measured in nonsurgically treated patients. We analyzed the influence of tumor volume on complete response (CR), overall survival (OS), and clear surgical margins also in primarily surgically treated patients. METHODS: In contrast-enhanced CTs, the tumor volumes of patients with incident HNSCC were measured. RESULTS: The tumor volumes of 259 patients were measured, of which 125 patients (48%) underwent primary surgery and 102 patients (84%) had clear margins. The tumor volume was not an independent factor for CR at the primary tumor site. Risk of death increased by 1.4% per mL of tumor volume (95% confidence interval [CI] 0.8%-2.0%; P < .001). The OS was better in patients treated with primary surgery, if the tumor volume was ≤12 mL (P < .001). Risk of involved margins increased by 4.5% per mL of tumor volume (95% CI 0.9%-8.3%; P = .003). The predicted probability of clear margins was ≥80% in tumor volumes ≤ 16 mL. CONCLUSION: The tumor volume had an impact on CR, OS, and clear margins. The tumor volume may also aid in selecting HNSCC treatment.

Optimized conformal paraaortic lymph node irradiation is not associated with enhanced renal toxicity.

BACKGROUND AND PURPOSE: For patients with gynecologic carcinomas, irradiation of paraaortic lymph nodes (PLNs) is a routine treatment concept. Planning target volumes (PTVs) individually optimized by radiation field delineations along the big vessels permit the inclusion of at least 97% of potentially involved PLNs. However, this novel treatment technique might increase radiation-induced nephrotoxicity. Therefore, the actual incidence of kidney damage after PLN irradiation has to be assessed in order to validate the safety of this treatment concept. PATIENTS AND METHODS: 19 patients were treated with irradiation alone (50.4 Gy; 5 x 1.8 Gy/week) and monitored for up to 90 months. Functional renal parameters, namely renal plasma flow (RPF) and glomerular filtration rate (GFR), were assessed by dynamic renal scintigraphy. Additionally, patients were clinically observed (i.e., hypertension, proteinuria) and calculations of normal-tissue complication probability (NTCP) values for nonuniform kidney irradiation were performed using the Lyman-Wolbarst algorithm. RESULTS: Two patients with anticipated moderate NTCP values (12.6% and 8.7%) showed slightly impaired RPF rates at 12, 24, and after 48 months of follow-up. Only one patient in the subgroup showing NTCP values > 50% (n = 9) developed a notable impairment of renal RPF. However, all patients including those with elevated complication probabilities exhibited neither impaired GFR nor clinically apparent symptoms related to a loss of functioning renal tissue from 12 to > 48 months post irradiation. CONCLUSION: Conformal irradiation of retroperitoneal lymph nodes with individual PTV delineation appears not to be associated with clinically relevant functional impairment of the kidneys.

Competing irradiation techniques for para-aortic lymph nodes: dose distribution and NTCP for the kidney.

PURPOSE: Partial coirradiation of both kidneys is an unavoidable consequence of adequate dose delivery in radiation therapy of para-aortic lymph nodes (PLN). Depending on total dose anteroposterior/posteroanterior (AP/PA), opposed-fields or multifield techniques are used. To optimize the treatment of potentially tumor-affected PLN with minimal kidney involvement, we calculated normal tissue complication probabilities (NTCPs) of coirradiated kidneys for four common irradiation techniques used in the PLN area. METHODS AND MATERIALS: Planning target volume (PTV) delineation was performed in computed tomography scans of 21 patients with a lateral safety margin of 3 cm from the aorta and 2 cm aside the vena cava. Ventral and dorsal margins of the PTV were delineated 2 cm from the vessels. As previously shown (Nevinny-Stickel M, et al. Int J Radiat Oncol Biol Phys 2000;48:147-151), PTVs optimized by these altered delineations permit inclusion of at least 97% of potentially involved PLN in contrast to standard delineations based on bony structures that are more likely to miss affected lymph nodes. The present study compared NTCPs for individual PTV-based treatment planning with NTCPs for standard planning based on bony structures. For each patient, four hypothetical treatment plans were created: (A) standard AP/PA opposed fields technique with lateral field margins along the tips of the transverse processes of the vertebral bodies; (B) individually planned AP/PA opposed fields with lateral field margins according to the optimized PTV; (C) standard four-field box technique with lateral width as described for (A), with dorsal borders at the center of the vertebral bodies and ventral margins 3 cm in front of the vertebrae; and (D) individually planned four-field box with lateral field margins according to the optimized PTV. Calculation of irradiation-induced complication probability values for nonuniform kidney irradiation was performed for model doses 19.8 Gy, 30.6 Gy, and 50.4 Gy according to the Lyman-Wolbarst model. RESULTS: No dose showed a statistically significant difference (p < 0.00833, corrected for six multiple interrelated comparisons) in the median of total organ kidney NTCPs between techniques A, C, and D, with technique D intermediately ranging between technique A and C (e.g., for 50.4 Gy: A: median, 0.39; range, 0.01-0.83; C: median, 0.27 range; 0.05-0.68; D: 0.36; range, 0.03-0.72). In comparison to techniques A, C, and D, the individually planned AP/PA opposed-fields technique (B) was accompanied by significantly higher and intolerable overall kidney NTCP rates (e.g., for 50.4 Gy: median, 0.68; range, 0.01-0.99). CONCLUSION: Conformal four-field planning with individually optimized PTVs (D) resulted in only moderate tissue complication probabilities in both kidneys with the advantage of providing significantly greater inclusion of potentially involved PLNs in comparison to accepted standard procedures (A and C).

Reproducibility of patient positioning for fractionated extracranial stereotactic radiotherapy using a double-vacuum technique.

BACKGROUND AND PURPOSE: Precise reproducible patient positioning is a prerequisite for conformal fractionated radiotherapy. A fixation system based on double-vacuum technology is presented which can be used for conventional as well as hypofractionated stereotactic extracranial radiotherapy. MATERIAL AND METHODS: To form the actual vacuum mattress, the patient is pressed into the mattress with a vacuum foil which can also be used for daily repositioning and fixation. A stereotactic frame can be positioned over the region of interest on an indexed base plate. Repositioning accuracy was determined by comparing daily, pretreatment, orthogonal portal images to the respective digitally reconstructed radiographs (DRRs) in ten patients with abdominal and pelvic lesions receiving extracranial fractionated (stereotactic) radiotherapy. The three-dimensional (3-D) vectors and 95% confidence intervals (CI) were calculated from the respective deviations in the three axes. Time required for initial mold production and daily repositioning was also determined. RESULTS: The mean 3-D repositioning error (187 fractions) was 2.5 +/- 1.1 mm. The largest single deviation (10 mm) was observed in a patient treated in prone position. Mold production took an average of 15 min (10-30 min). Repositioning times are not necessarily longer than using no positioning aid at all. CONCLUSION: The presented fixation system allows reliable, flexible and efficient patient positioning for extracranial stereotactic radiotherapy.