Concurrent Induction Chemotherapy Research Articles

Outcomes of Hypofractionated Radiotherapy with Induction or Sequential Chemotherapy for Unresectable Stage III Non-Small Cell Lung Cancer: Single Institution Experience

The standard of care for unresectable stage III non-small cell lung cancer (NSCLC) patients not candidates for concurrent chemotherapy (CT) and radiotherapy (RT) is not well established. Hypofractionated RT (hRT) can be used after CT induction, or, as a bridge to sequential CT to offer a curative intent treatment regimen. Tumor and nodal proximity to mediastinal structures plays an important role regarding the degree of safe hypofractionation. There is limited published evidence related the benefits of hRT combined with induction or sequential CT among this group of patients. We analyzed the outcomes of stage III NSCLC receiving a hRT regimen of 52.5 Gy in 15 fractions alone, or with either induction or sequential CT. In this retrospective review, patients with stage III NSCLC receiving hRT 52.5 Gy in 15 fractions between 2008 and 2020 were included for analysis. Patients were separated into three cohorts: i) hRT alone, ii) induction CT followed by hRT, and iii) hRT followed by sequential CT. Overall survival (OS) and radiation toxicity (CTCAE v5.0) were analyzed for all 3 cohorts. Patients for whom sequential chemotherapy was planned, but not delivered, were included in cohort ii) through intention-to-treat analysis. The OS at 2 years was statistically evaluated using a log-rank test with alpha set at 0.05. Eighty-three patients met criteria for analysis with 35, 30, and 18 patients respectively in cohorts i), ii), and iii). Median age at treatment was 75 (43-91) with 53% of patients being men and 43% women. Tumor histology varied between adenocarcinoma (43%), squamous cell carcinoma (44%), and others (13%). The median/2-year OS for cohorts i), ii), and iii) was 8 mo/19%, 25 mo/50%, and 17 mo/72% respectively. OS between any chemotherapy and no chemotherapy was statistically significant (p = 6.1x10-7) while the timing of chemotherapy did not reach statistical significance (p = 0.15). RT was overall well tolerated with grade 1-2 fatigue being the most common side effect (81%), 1 patient had grade 3 pneumonitis, and 1 patient had a rib fracture. Among patients with stage III NSCLCs, moderately hRT of 52.5 Gy in 15 fractions, with either induction or sequential CT appears to provide a survival advantage compared to hRT alone, with an acceptable side-effect profile. The 2-year OS reported here is similar to other published hRT regimens (SOCCAR trial) and conventional fractionation (RTOG0617). Conclusions are limited by the retrospective nature of the study, and the introduction of immunotherapy (IO) for stage III NSCLC in 2019 in Canada. Future work will focus on evaluating dosimetry, the impact of IO, and, patients not included in this analysis that also received this regimen (oligometastasis, locoregional failure, other stages).

Chemoradiotherapy versus radiotherapy alone following induction chemotherapy for elderly patients with stage III lung cancer.

PurposeIt is unclear whether adding concurrent chemotherapy (CT) to definitive radiotherapy (RT) following induction CT is a tolerable and cost effective treatment for non-small-cell lung cancer (NSCLC) patients aged 70 years or older with comorbidities. This study evaluated the actual clinical outcomes between concurrent chemoradiotherapy (CCRT) and RT alone following induction CT or not in patients (≥70 years) in a single institution’s clinical practice.Materials and MethodsA total of 82 patients with unresectable stage III NSCLC between 2004 and 2016 were retrospectively analyzed. Their treatment tolerance and clinical outcomes such as overall survival (OS), locoregional recurrence (LRR), treatment toxicities and distant metastasis (DM) were evaluated. Early mortality rates were also evaluated as 4-month mortality after RT.ResultsFifty-four patients received CCRT and 28 patients received RT alone. Induction CT before RT was performed for 68.5% and 50.0% in CCRT and RT alone groups. Treatment tolerance was significantly worse in CCRT (p = 0.046). The median survival was 21.1 and 18.1 months for CCRT and RT alone, which was not statistically significant. LRR and DM were also not different. Most early deaths after CCRT were attributed to non-cancer-related mortality. Acute esophagitis of grade ≥2 occurred more following CCRT (p = 0.017). In multivariate analysis, a Charlson Comorbidity Index (CCI) of ≥5 and a weight loss of ≥5% after RT were associated with poor OS. The factors adversely affecting 4-month survival were a CCI of ≥5 and CCRT.ConclusionThere were no significant differences in OS, LRR, and DM between CCRT and RT alone treatment in elderly patients. However, there was a poorer tolerance and higher incidence of acute esophagitis in the CCRT group. Specifically, when the patients had a CCI of ≥5, RT alone seems to be reasonable with a low probability of early death.

Potential improvement of tumor control probability by induction chemotherapy for advanced nasopharyngeal carcinoma

Purpose To assess the reduction of tumor bulk and improvement of tumor control probability (TCP) by using induction chemotherapy for advanced nasopharyngeal carcinoma (NPC). Materials and methods From February to December 2005, 20 patients with Stage III–IVB NPC were treated with induction-concurrent chemotherapy and intensity-modulated radiotherapy with accelerated fractionation. Combination of cisplatin and 5-fluorouracil was used in the induction phase and single agent Cisplatin in the concurrent phase. All patients were irradiated at 2 Gy per fraction, 6 daily fractions per week, to a total dose of 70 Gy. Results Nineteen (95%) patients completed all 3 cycles of induction chemotherapy and 90% had ⩾2 cycles of concurrent chemotherapy. Induction chemotherapy achieved significant down-staging of T-category in 35% of patients ( p = 0.016) and reduction of gross tumor volume (GTV_P) from 55.6 to 22.9 cc (mean 61.4%, p < 0.001). Although the mean radiation dose did not show any substantial change, the volume within GTV_P that failed to reach 70 Gy was reduced from 10.2% to 3.8% ( p = 0.017). The estimated local TCP increased from 0.83 to 0.89 ( p = 0.002). Conclusions Induction chemotherapy using cisplatin–5-fluorouracil could significantly reduce tumor bulk leading to potential improvement in tumor control.

Treatment of stage IV(A-B) nasopharyngeal carcinoma by induction-concurrent chemoradiotherapy and accelerated fractionation

To explore a more effective strategy for treating nasopharyngeal carcinoma with extensive locoregional disease. Between October 1998 and January 2003, 49 patients with Stage IV(A-B) disease infiltrating or abutting neurologic structures were treated with induction-concurrent chemotherapy and accelerated radiotherapy (RT). A combination of cisplatin and 5-fluorouracil was used in the induction phase and single-agent cisplatin in the concurrent phase. All patients were irradiated with conformal techniques at 2 Gy/fraction, six daily fractions weekly, to a total dose of 70 Gy. Although 92% of patients had one or more acute toxicities Grade 3 or worse, 96% completed the whole course of RT, and 92% had five or more cycles of chemotherapy. The great majority of toxicities were uneventful, but 1 patient died of neutropenic sepsis. With a median follow-up of 3.1 years, 20 patients had failure at one or more sites and 15 patients died. The 3-year locoregional and distant failure-free rate was 77% and 75%, respectively, and the overall survival rate was 71%. At last follow-up, 27% of patients had developed late Grade 3 or worse toxicity (24% were hearing impairments), but none had radiation-induced neurologic damage. The current strategy achieved encouraging results for this poor prognostic group, and confirmation of the therapeutic gain by a prospective randomized trial is warranted.

Long term results of induction carboplatin (CBDCA) and docetaxel (DOC) with concurrent radiation in early-stage non-small cell lung cancer (NSCLC)

7237 Background: Despite surgical resection, patients with clinical T2N0, T1–2N1 and T3N0 NSCLC have poor 5-year survivals (30% to 50%). Since a significant proportion of patients with early-stage NSCLC experience distant as well as loco-regional recurrences, multimodality therapy has recently been encouraged in an attempt to prolong survival. We conducted a phase II study to determine the feasibility and efficacy of induction CBDCA and DOC with concurrent radiation in early-stage NSCLC. Methods: Eligible were patients with previously untreated stage IB, and II histologically proven NSCLC. Clinical nodal stage was assessed by mediastinoscopy, mediastinotomy and CT imaging. A negative biopsy result of all enlarged mediastinal lymph nodes (shortest diameter ≥1.0 cm on CT scan) was required. CBDCA (AUC=5) and DOC (60 mg/m2) were administered once every 3 weeks for 2 cycles concurrent with 40 Gy (2Gy/fx/day) radiation. In patients with no evidence of disease progression thoracotomy was performed 3–5 weeks later. Results: Forty patients were entered into the study between 02/99 and 07/01. Patient characteristics included M/F: 27/13; median age (range): 59 (39–73); clinical stage T2N0/T1N1/T2N1/T3N0: 21/2/13/4; adeno/squamous/large cell: 26/12/2. Despite a high rate of grade 3/4 neutropenia (88%), no serious infectious events were observed. All the patients completed induction chemoradiotherapy and major responses were observed in 29 (73%). Of these, thirty-nine patients underwent thoracotomy and were resected completely. The type of operation was pneumonectomy in 2 and lobectomy in 37. A pathologic response (T or N downstaging) was identified in 30 (77%) and 10 (26%) had no residual disease. One patient had a bronchopleural fistula after left pneumonectomy. Median follow up was 57 months. Actuarial 3-year and estimated 5-year survivals were 82.5% and 69.9%, respectively. Three-year and 5-year disease free survivals were 76.9% and 71.0%, respectively. Conclusions: Induction concurrent chemotherapy (CBDCA + DOC) with thoracic radiotherapy is feasible, tolerable and deserves further evaluation in a randomized phase III study. No significant financial relationships to disclose.