Testing the Timing: Time Factor in Radiation Treatment for Head and Neck Cancers.

OPINION STATEMENT: Overall radiation treatment time has long been recognized as an important factor in head and neck tumor control. The concern of tumor growth in waiting time either before starting radiotherapy or during treatment is substantial given its negative impact on clinical outcome. There is an overwhelming evidence that increasing the time to initiate treatment increases the tumor burden and worsens the prognosis. This effect is more pronounced especially in patients with an early stage cancer disease. Delay in treatment initiation is contributed by both health care- and patient-related factors. Health care-related factors include advancement in diagnostic modalities and transfer of patient to academic health care centers accompanied by delayed referrals and long-awaited appointments. Patient-related factors include delayed reporting time and socioeconomic factors. An efficient transition of care along with access of cancer care modalities to community health care centers will not only improve the quality of care in secondary health care centers but also help decrease the patient burden in tertiary centers. A quick and well-structured multidisciplinary appointment program is fundamental in shortening the time required for patient referrals, thus increasing the optimal survival time for Head and Neck cancer patients with early initiation of treatment.

Intensity-modulated radiotherapy with simultaneous modulated accelerated boost technique and chemotherapy in patients with nasopharyngeal carcinoma.

BACKGROUND: To present our experience of intensity-modulated radiotherapy (IMRT) with simultaneous modulated accelerated radiotherapy (SMART) boost technique in patients with nasopharyngeal carcinoma (NPC). METHODS: Sixty eight patients of NPC were treated between April 2006 and December 2011 including 45 males and 23 females with mean age of 46 (range 15-78). Stage distribution was; stage I 3, stage II 7, stage III 26 and stage IV 32. Among 45 (66.2%) evaluated patients for presence of Epstein-Barr virus (EBV), 40 (88.8%) were positive for EBV. Median radiation doses delivered to gross tumor volume (GTV) and positive neck nodes were 66-70 Gy, 63 Gy to clinical target volume (CTV) and 50.4 Gy to clinically negative neck. In addition 56 (82.4%) patients with bulky tumors (T4/N2+) received neoadjuvant chemotherapy 2-3 cycles (Cisplatin/Docetaxel or Cisplatin/Epirubicin or Cisplatin/5 Flourouracil). Concurrent chemotherapy with radiation was weekly Cisplatin 40 mg/m2 (40 patients) or Cisplatin 100 mg/m2 (28 patients). RESULTS: With a median follow up of 20 months (range 3-43), one patient developed local recurrence, two experienced regional recurrences and distant failure was seen in 3 patients. Estimated 3 year disease free survival (DFS) was 94%. Three year DFS for patients with EBV was 100% as compared to 60% without EBV (p = 0.0009). Three year DFS for patients with undifferentiated histology was 98% as compared to 82% with other histologies (p = 0.02). Acute grade 3 toxicity was seen as 21 (30.9%) having G-III mucositis and 6 (8.8%) with G-III skin reactions. Late toxicity was minimal and loss of taste was seen in 3 patients (7.5%) at time of analysis. CONCLUSIONS: IMRT with SMART in combination with chemotherapy is feasible and effective in terms of both the clinical response and safety profile. EBV, histopathology and nodal involvement were found important prognostic factors for locoregional recurrence.

Radiotherapy and Limb-Sparing Surgery in the Management of Localized Soft Tissue Sarcomas: Tertiary Care Center Experience From Pakistan.

PURPOSE: When combined with radiotherapy, limb salvage surgery is an alternative to amputation. This study sought to determine the limb-sparing treatment outcomes in patients diagnosed with soft tissue extremity sarcomas treated at our institution. MATERIALS AND METHODS: All adult patients with extremity soft tissue sarcoma treated with the radical limb salvage strategy at Shaukat Khanum Memorial Cancer Hospital and Research Canter, Lahore, Pakistan, between January 2017 and December 2019 were retrospectively assessed. RESULTS: A total of 122 patients were included in the study. The mean age was 42 years (range 19-82), and 64 (52.5%) were males. The majority of patients, 65 (53.3%), were diagnosed with stage III and grade III disease according to American Joint Committee on Cancer TNM classification (Eighth edition). The most common surgical modality was wide local excision that was performed in 106 (86.9%) patients. Adjuvant radiation treatment was given in 111 (91%) patients, whereas 11 (9%) patients received neoadjuvant radiation treatment. The mean dose was 58 Gy (range: 46-66 Gy). Eighty-two (67.2%) of the patients were disease-free on post-treatment radiologic scans with disease recurrence observed in 40 (32.8%) patients. The median disease-free survival was 8 months (95% CI, 5.45 to 10.55). Local recurrence and distant metastases developed in 16 (13%) and 24 (20%) patients, respectively. CONCLUSION: About two thirds of patients with extremity soft tissue sarcoma were successfully treated with limb salvage strategy, surgery, and radiation therapy. However, high rate of relapse warrants further novel strategies in this patient population.

Single institution experience treating adrenal metastases with stereotactic body radiation therapy.

OBJECTIVE: The objective of the study is to present our experience of treating adrenal metastases using stereotactic body radiation therapy (SBRT). MATERIALS AND METHODS: We retrospectively reviewed patients with adrenal metastases treated using SBRT from 2001 to 2014. Response Evaluation Criteria in Solid Tumors v1.1 was used. Maximum tumor response was defined as the greatest percentage tumor reduction noted on two or more post-SBRT CT scans. RESULTS: We identified 44 patients (median age 61.3 years, range: 25.8-85), with 54 adrenal metastases; primary diagnoses include non-small cell lung cancer (28 patients and 38 lesions), small cell lung cancer (1 patient), hepatocellular carcinoma (6 patients), and other (9 patients). Treatment was delivered in single (16 lesions, median dose 18 Gy [14-18]) or multiple fractions (38 lesions, median dose 30 Gy [16-40]). Median planning target volume was 49.65cc (3.21-984.54). Median response at first post-SBRT follow-up (median 1.65 months (m) (0.33-5.37), n = 46 lesions) was 10.8% with 91.3% local control. Median maximum tumor response was 31.8% (n = 32 lesions) at median follow-up of 5.4 m (0.9-44.8) with 96.6% local control. The response was comparable regardless of tumor histology or treatment fractionation. No patients experienced Grade 3/4 acute toxicities. One patient with a history of naproxen use required suturing with omental patch placement for perforated pyloric ulcer 14 m post-SBRT (18 Gy in single fraction) to the right adrenal metastasis; this region received <5 Gy. Ten patients treated for pain with available follow-up obtained relief. CONCLUSIONS: SBRT is a safe and efficacious treatment for adrenal metastases, demonstrating local tumor control. Further study of the impact on survival and quality of life is warranted.

Time abides long enough for those who make use of it.

Increased treatment package time is an independent poor prognostic factor for outcomes in head and neck squamous cell carcinoma (HNSCC). Similarly the timeliness of treatment initiation is a risk factor for disease recurrence. Despite these well-known issues, the timeliness of treatment initiation is actually worsening in the United States and the expeditious completion of radiation treatments continues to be difficult secondary to a number of patients and treatment related issues. This analysis evaluates the current data on treatment intervals in the management of head and neck cancer. Rapid staging/diagnosis of head and neck cancer, appropriate referrals to providers qualified to treat said cancer, and expeditious treatment completion remains the most cost-effective, widely applicable method to improve outcomes in head and neck cancer.

A treatment planning comparison between a novel rotating gamma system and robotic linear accelerator based intracranial stereotactic radiosurgery/radiotherapy.

To compare the dosimetric parameters of a novel rotating gamma ray system (RGS) with well-established CyberKnife system (CK) for treating malignant brain lesions. RGS has a treatment head of 16 cobalt-60 sources focused to the isocenter, which can rotate 360° on the ring gantry and swing 35° in the superior direction. We compared several dosimetric parameters in 10 patients undergoing brain stereotactic radiosurgery including plan normalization, number of beams and nodes for CK and shots for RGS, collimators used, estimated treatment time, D 2 cm and conformity index (CI) among two modalities. The median plan normalization for RGS was 56.7% versus 68.5% (p = 0.002) for CK plans. The median number of shots from RGS was 7.5 whereas the median number of beams and nodes for CK was 79.5 and 46. The median collimator's diameter used was 3.5 mm for RGS as compared to 5 mm for CK (p = 0.26). Mean D 2 cm was 5.57 Gy for CyberKnife whereas it was 3.11 Gy for RGS (p = 0.99). For RGS plans, the median CI was 1.4 compared to 1.3 for the CK treatment plans (p = 0.98). The average minimum and maximum doses to optic chiasm were 21 and 93 cGy for RGS as compared to 32 and 209 cGy for CK whereas these were 0.5 and 364 cGy by RGS and 18 and 399 cGy by CK to brainstem. The mean V12 Gy for brain predicting for radionecrosis with RGS was 3.75 cm3 as compared to 4.09 cm3 with the CK (p = 0.41). The dosimetric parameters of a novel RGS with a ring type gantry are comparable with CyberKnife, allowing its use for intracranial lesions and is worth exploring in a clinical setting.

Concurrent chemoradiation for resected gall bladder cancers and cholangiocarcinomas.

BACKGROUND: Gallbladder cancer (GBC) and cholangiocarcinoma (CCA) are rare entities with relatively poor prognoses. We compared treatment outcomes of definitive resection with or without neoadjuvant therapy in GBC and CCA patients. METHODS: All non-metastatic GBC and CCA patients at a single institution who underwent definitive resection from 1992-2016 were analyzed. We compared overall survival (OS), locoregional failure (LRF) and distant failure (DF) in patients who received neoadjuvant therapy (chemotherapy and/or radiation) versus those who did not receive neoadjuvant treatment. OS was analyzed using the Kaplan-Meier method and log rank tests. Cox proportional hazard models were used to analyze time to recurrence. RESULTS: Out of 128 patients, 90 had GBC and 38 had CCA, 25 patients (27%) among GBC and 8 patients (21%) with CCA were T3, T4 or node positive. Overall, 52 (40%) GBC and 25 (20%) CCA patients received neoadjuvant treatment, chemotherapy alone 60 patients (47%) or radiation with or without chemotherapy 17 patients (13%). Chemotherapy was single agent in 44 patients (34%) and multi-agent in 25 (20%). The median OS for GBC patients was 3.1 years with 2.6 years for no neoadjuvant group and 3.1 years for neoadjuvant group (P=0.6786). Median OS was 2.6 years for CCA patients, 3.6 years for no neoadjuvant therapy versus 2.0 years for neoadjuvant group (P=0.1613). There was a trend towards increased DF in patients with CCA and GBC receiving neoadjuvant therapy: HR 2.74, 95% CI, 0.73-10.3, P=0.14 and 0.92, 95% CI, 0.44-1.93, P=0.82 respectively. The hazard ratio for time to LRF in CCA patients receiving neoadjuvant treatment was 3.17, 95% CI, 0.62-16.31, P=0.16 whereas HR was 0.15, 95% CI, 0.10-1.76, P=0.23 for GBC patients. Among GBC patients, the pattern of first failure was locoregional in 8 (10%) having 3 LRF in neoadjuvant group (2 with chemotherapy, 1 with CRT, 0 with RT alone) as compared to 5 in adjuvant group. Among 28 (35%) patients with DF first, 15 patients received neoadjuvant therapy versus 13 patients in non-neoadjuvant group. In CCA patients, LRF occurred first in 6 patients receiving neoadjuvant treatment (3 with chemotherapy, 1 with CRT, 2 with RT alone) as compared to 2 patients who were treated with non-neoadjuvant CRT. DF was the first site of failure in 9 patients treated with neoadjuvant CRT (8 with chemotherapy, 0 with CRT and 1 with RT alone) as compared to 4 patients without neoadjuvant treatment. CONCLUSIONS: In this retrospective data set, a trend towards better survival was seen in adjuvantly treated CCA patients, but not in GBC patients. Recurrence patterns also appear different among the two, which might be attributed to treatment modality used, patient selection or unmeasured factors. KEYWORDS: Gallbladder cancer (GBC); cholangiocarcinoma (CCA); neoadjuvant; resection; chemoradiation; chemotherapy.