Vaginal-cuff control and toxicity results of a daily HDR brachytherapy schedule in endometrial cancer patients

Purpose

To analyze the vaginal-cuff local control (VCC) and toxicity in postoperative endometrial carcinoma patients (EC) underwent high-dose-rate brachytherapy (HDR-BT) administered daily.

Materials and methods

154 consecutive patients received postoperative HDR-BT for EC from January 2007 to September 2011. FIGO-staging I–IIIC2 patients were divided into two groups according to risk classification: Group 1 (94/154) included high-risk or advanced disease patients and Group 2 (60/154) included intermediate-risk EC patients. Group 1 underwent external beam irradiation (EBI) plus HDR-BT (2 fractions of 5 Gy) and Group 2 underwent HDR-BT alone (4 fractions of 5 Gy). Toxicity evaluation was done with RTOG scores for bladder and rectum, and the objective criteria of LENT–SOMA for vagina.

Results

With a median follow-up of 46.7 months (36.6–61 months) only two patients developed vaginal-cuff recurrence in Group 1 (2.1 %) and none in group 2 (0 %). Early toxicity in Group 1 appeared 5.3 % in rectum, 7.5 % in bladder (G1–G2) and 2.1 % in vagina (G1); late toxicity was present in 7.3 % in rectum (all G1–G2 but 1 G3) and in 27.7 % in vagina (all G1–G2 but one G4). In Group 2, 6.7 % developed acute G1–G2 bladder and 6.6 % acute vaginal (G1–G2) toxicity. No late rectal or bladder toxicity was observed; 21.7 % of G1–G2 presented late problems in vagina.

Conclusions

The present HDR-BT schedule of 2 fractions of 5 Gy after EBI and 4 fractions of 5 Gy administered daily showed excellent results in terms of VCC and toxicity.

     

Three or four fractions per week in postoperative high-dose-rate brachytherapy for endometrial carcinoma. The long-term results on vaginal relapses and toxicity

Background

High-dose-rate brachytherapy (HDR-BT) is an accepted part of treatment for endometrial carcinoma and is usually performed in 1–2 fractions per week using different total doses and doses per fraction. To reduce the overall treatment time, HDR-BT was administered with a 3–4 days/week schedule.

Patients and methods

From June 2003 to December 2008, 164 patients with stage I-IIIc endometrial carcinoma were treated with HDR-BT (4–5 Gy per fraction). The patients were divided into two groups; Group 1 (40/164 patients) was treated with HDR-BT alone (6 fractions; 4 fractions/week) and Group 2 (124/164 patients) was treated with both (External Beam Radiotherapy [EBRT] + HDR-BT: 3 fractions/week). Complications were analyzed using RTOG scores for rectum and bladder and the objective scores of LENT-SOMA for vaginal complications.

Results

The mean followup was 48 months. In Group 1, 35 % of patients underwent treatment in ≤10 days and 65 % in >10 days. In Group 2, 53.2 % received treatment in ≤5 days and in 46.8 % in >5 days. Vaginal relapse was observed in only two patients (1.2 %), both having received adjuvant EBRT + HDR-BT. Acute vaginal toxicity appeared in 8.5 % and late vaginal toxicity in 20.7 % of patients with 13.4 % being G1, 6.7 % G2 and only 0.6 % being G4. No statistically significant differences were found in complications in either brachytherapy group regardless of the overall time.

Conclusion

In our series, three fractions given in 3–5/days after EBRT or six fractions in 10 days, is a safe regimen in terms of complications and local control.     

Do comorbidity influences acute toxicity and outcome in elderly patients with endometrial cancer treated by adjuvant radiotherapy plus brachytherapy?

Purpose

To correlate comorbidity and acute radiation toxicity in elderly patients treated with adjuvant external beam radiotherapy (EBRT) plus brachytherapy-high dose rate (HDR-BRT) for endometrial cancer (EC).

Methods

Endometrial cancer patients over 65 were treated and evaluated for comorbidity assessment with ACE-27 and Charlson comorbidity index (CCI). EBRT total dose was 45–50.4 Gy (1.8 Gy/day). The vault vagina boost of dose was performed by HDR-BRT with 2/3 fractions with a total dose of 10–15 Gy.

Results

From 2008 to 2011, 35 patients were analyzed. Eighteen patients (51.43 %) had not ACE-27 comorbidity; while 27 patients (77.14 %) had CCI lower than three. During treatment, acute toxicity was mild and not influenced by the comorbidity score. Two-year Progression Free and Overall Survival were 69 and 80 %. ACE-27 and CCI did not affect progression-free survival (p = 0.51, p = 0.3) and OS (p = 0.26, p = 0.5).

Conclusion

External beam radiotherapy plus BRT-HDR are well tolerated in EC elderly with good performance status and low comorbidity profile.     

Hypofractionated helical tomotherapy using 2.5–2.6 Gy daily fractions for localized prostate cancer

Background

The purpose of this study is to evaluate the tolerability of hypofractionated helical tomotherapy (HT) in the treatment of localized prostate cancer.

Materials and methods

We evaluated 48 patients with primary adenocarcinoma of the prostate (cT1-T3N0M0) who were treated with hypofractionated HT from August 2008 through July 2011. Hypofractionated regimens included: 68.04 Gy at 2.52 Gy/fraction, 70 Gy at 2.5 Gy/fraction, and 70.2 Gy at 2.6 Gy/fraction. Genitourinary (GU) and gastrointestinal (GI) toxicity was scored using the Radiation Therapy Oncology Group scoring system.

Results

Thirty-two patients were treated with 68.04 Gy, 5 patients with 70 Gy, and 11 with 70.2 Gy. The median age at diagnosis was 69 years (range 49–87) and the median follow-up 11 months (range 7–40). Grade 2 acute GI toxicity occurred in 9 patients (19 %). No grade 3 or higher acute GI toxicity was observed. Grade 2 and 3 acute GU toxicities occurred in 19 and 6 % of patients, respectively. The incidence of late grade 2 GI and GU toxicity was 4 and 2 %, respectively. No grade 3 or higher late toxicities were observed. Multivariate analysis showed that patients treated at 2.6 Gy/fraction or those who received a total radiation dose ≥70 Gy had higher rates of grade ≥2 acute GU toxicity (P = 0.004 and P = 0.048, respectively).

Conclusion

Hypofractionated HT in the treatment of localized prostate cancer is well tolerated with no grade 3 or higher early or late GI and GU toxicities. Further research is needed to assess definitive late toxicity and tumor control.     

Prognostic factors for acute toxicity in prostate cancer patients treated with high-dose hypofractionated radiotherapy

Purpose

To prospectively study acute genitourinary (GU) and gastrointestinal (GI) toxicity during hypofractionated radiotherapy.

Patients and materials

One-hundred and seventy-one consecutive men with cT1-T3cN0cM0 prostate cancer were treated at 2.6 Gy/fraction to a total dose of 67.6 for low risk (EQD2 = 79 Gy) and 70.2 Gy for intermediate–high risk (EQD2 = 82 Gy) over 5.2–5.4 weeks (α/β 1.5). Acute toxicity was scored according to RTOG/EORTC toxicity extended criteria after completing a 22-item questionnaire (basal, weekly, at 6 months).

Results

Minimum and median follow-up were 36 and 54.2 months, respectively. GU toxicity grades 0, 1, 2 and 3 were found in 30.4, 37, 32 and 0.6 % of patients, respectively. The figures for grades 0, 1, 2 and 3 GI toxicity were 66, 24, 10 and 0 %. The highest degree of acute reactions was reached at 4–5 weeks. At 6 months, 15 % of patients had GU toxicity (11 % grade 1, 4 % grade 2) and 5.8 % GI toxicity (5.3 % grade 1, 0.5 % grade 2). Multivariate analysis shows that bladder volume receiving ≥65 Gy (V ₆₅) is associated with an increased risk of GU complications (p = 0.017, HR = 1.143, 95 % CI = 1.025–1.276), while history of TURP is linked to lower risk (p = 0.002, HR = 0.310, 95 % CI 0.004–0.370). Mean rectal dose (p = 0.013, HR = 1.089, 95 % CI 1.018–1.116) and total dose (p = 0.019, HR = 0.734, 95 % CI 0.567–0.950) are significantly related to GI toxicity.

Conclusions

This 5-week dose-escalation hypofractionated radiotherapy schedule that uses 3D-conformal radiotherapy without IGRT has resulted in <1 % grade 3 acute complications. Our study suggests that reducing the mean rectal dose and the bladder V ₆₅ helps prevent acute toxicity. TURP before radiotherapy was associated with lower acute GU toxicity.     

Initial experience with stereotactic body radiation therapy for localized prostate cancer using helical tomotherapy

Purpose

Single-institution single-arm prospective study. Endpoint: To assess whether there are more than 5 % of men having grade 3 GU or any grade 3 GI acute toxicity during stereotactic body radiation therapy (SBRT) for prostate cancer using helical tomotherapy.

Methods

Since May 2012, 17 prostate cancer patients were treated with helical tomotherapy. The exclusion criteria used are the following: Gleason score ≥8, PSA >20 ng/ml, cT3b-4, IPSS ≥20 and history of acute urinary retention. CTV included the prostate gland and 1 cm of seminal vesicles in the low-risk group (LR) or the seminal vesicles completely in the intermediate (IR) and high-risk (HR) NCCN groups. CTV margins ranged from 2 to 8 mm, while PTV margins were 2 to 9 mm. Patients received eight fractions of 5.48 Gy (LR) or 5.65 Gy (IR, HR) on alternate days. Total equivalent doses at 2 Gy per fraction are 87.4 for LR and 92.3 Gy for IR–HR using an α/β value of 1.5. Correspondent figures for a α/β of 3 are 74.3 Gy and 78.2 Gy, respectively. Megavoltage CT (MVCT) for on-line correction was taken before every fraction.

Results

The patient distribution by risk group is 29, 47 and 24 % for LR, IR and HR, respectively. 82 % received neoadjuvant-concomitant hormonal therapy. Acute GU toxicity grade 1, 2 and 3 was found in 70, 6 and 0 % of men. GI toxicity was observed in 50, 0 and 0. After 136 MVCT, the standard deviation of the mean individual corrections in the anterior–posterior direction was 2.5 mm.

Conclusion

SBRT for prostate cancer using helical tomotherapy is feasible. Initial results show an early toxicity profile no worse than SBRT delivered with robotic radiosurgery or conventionally fractionated radiotherapy.     

Outcome and toxicity using helical tomotherapy for craniospinal irradiation in pediatric medulloblastoma

Purpose

The objective of this study is to evaluate the tolerability and outcome of craniospinal irradiation (CSI) with helical tomotherapy (HT) in the treatment of medulloblastoma.

Methods

We evaluated 19 consecutive patients with primary medulloblastoma who were treated with HT from 2007 through 2010. HT regimens to the neuroaxis included: 23.4 Gy at 1.8 Gy/fraction (N = 10), 36 Gy at 1.8 Gy/fraction (N = 7), and 39 Gy bid at 1.3 Gy/fraction (N = 2). The tumor bed received 54–60 Gy. Potential associations between patient, treatment, and toxicity factors and overall survival (OS) were assessed in univariate analyses using the Cox proportional hazards model. Spearman’s rank correlation coefficient was used to correlate potential risk factors with the grade of acute toxicity.

Results

The median age at diagnosis was 5 years (range 2–14) and the median follow-up for alive patients (N = 14) 40 months (range 10–62). Two- and three-year overall survival was 75 and 68 %, respectively. The most common acute toxicity was hematological (79 %), being grade 2 and grade 3 in 4 (21 %) and 11 (58 %) cases, respectively. No grade ≥2 late toxicities were observed. Higher grades of acute body toxicity were found in older children (P = 0.004). Longer time between diagnosis and radiation therapy was correlated with shorter OS (P = 0.03). In addition, higher grades of acute thrombocytopenia were associated with shorter OS (P = 0.03).

Conclusions

CSI delivered with HT for medulloblastoma is well tolerated with low rates of severe acute toxicity. Further research is necessary to assess late toxicity with a longer follow-up.     

The impact of prostate gland dimension in genitourinary toxicity after definitive prostate cancer treatment with moderate hypofractionation and volumetric modulated arc radiation therapy

Purpose

To analyze clinical-dosimetric predictors of genitourinary (GU) toxicity in a cohort of prostate cancer (PC) patients treated with moderate hypofractionation and simultaneous integrated boost (SIB) using volumetric modulated arc therapy (VMAT) technique.

Materials and methods

60 patients were selected. Patients were stratified into low (43 %), intermediate (30 %) and high-risk (27 %) groups. Low-risk patients received 73.5 Gy to PTV1; intermediate-risk received 73.5 Gy to PTV1 and 60 Gy to PTV2; high-risk received 73.5 Gy to PTV1, 60 Gy to PTV2, and 54 Gy to PTV3. All patients were treated in 30 fractions. Androgen deprivation therapy (ADT) was prescribed upfront in intermediate and high-risk categories. Toxicity was scored according to Common Terminology Criteria for Adverse Events v4.0 scoring system.

Results

Median follow-up was 30 months (range 16–36 months). GU acute toxicity was recorded as followS: G0 = 16/60 (27 %), G1 = 18/60 (30 %); G2 = 26/60 (43 %). GU late toxicity was recorded as follows: G0 = 20/60 (34 %); G1 = 29/60 (48 %); G2 = 11/56 (18 %). The risk of acute G2 GU toxicity was three times higher for prostate volume ≥80 cc. In 60 % of the patients with a prostate volume ≥80 cc, the first 3 weeks are at particular risk for toxicity onset. In the late setting, no statistical significance was found between GU toxicity and prostate gland dimension.

Conclusion

Prostate volume ≥80 cc resulted a predictive factor of acute G2 GU toxicity, in moderate hypofractionation and volumetric modulated arc radiation therapy for definitive PC.

     

Comparison of hypofractionated and conventionally fractionated whole-breast irradiation for early breast cancer patients: a single-institute study of 1,098 patients

Purpose

To evaluate the efficacy and safety of hypofractionated whole-breast irradiation (HF-WBI) compared with conventionally fractionated (CF) WBI.

Materials and methods

Patients with early breast cancer (stages 0–II and <3 positive lymph nodes) who had undergone breast-conserving surgery were eligible for the HF-WBI study. HF-WBI was administered at 43.2 Gy in 16 fractions over 3.2 weeks to the whole breast with an additional tumor-bed boost of 8.1 Gy in 3 fractions over 3 days for positive surgical margins or those <5 mm. CF-WBI was administered at 50 Gy in 25 fractions over 5 weeks to the whole breast with an additional tumor-bed boost of 16 Gy in 8 fractions over 1.4 weeks to 6 Gy in 3 fractions over 3 days, depending on margin status.

Results

From April 1, 2006, to December 31, 2010, 717 patients were registered and 734 breasts were treated by HF-WBI. In the same period, 381 patients and 393 breasts who matched the study criteria chose CF-WBI, so the total number of patients in this comparison was 1,098. Grade 2 acute skin reactions were observed for 24 patients (3 %) in the HF-WBI group and 53 patients (14 %) in the CF-WBI (p < 0.001) group. The median follow-up period was 27 months. Two cases of intrabreast tumor recurrence were observed in each treatment group. Regional lymph node recurrence was observed in 1 HF-WBI patient and 2 CF-WBI patients.

Conclusion

HF-WBI is superior to CF-WBI in terms of acute skin reaction and has the same short-term efficacy.     

Image-guided intensity-modulated radiotherapy for patients with locally advanced gastric cancer: a clinical feasibility study

Background

The aim of this study was to determine the medical and technical feasibility of intensity-modulated radiotherapy (IMRT) in high-risk nonmetastatic gastric cancer stage II and III after primary gastrectomy and D2 lymphadenectomy.

Methods and materials

A prospective nonrandomized phase II trial was performed on 25 consecutive patients with gastric cancer with high risk (T3–4, N1–3, G2–3, R0–1). The dose delivered was 45 Gy (1.80 Gy per fraction) in IMRT technique. Concurrent 5-fluorouracil-based chemotherapy at 225 mg/m² was administered as a continuous intravenous infusion. Primary endpoints were acute gastrointestinal toxicity (CTC 4.0) and technical feasibility of IMRT in regard to dose planning and radiation delivery.

Results

Early acute events were defined as clinical and chemical adverse effects of IMRT and concurrent chemotherapy during treatment. By definition, 90 days after the end of IMRT has been evaluated as acute-phase toxicity. No patient had grade 4 or higher acute adverse events. Clinical grade 3 toxicity occurred in two patients (8 %) with diarrhea and in one case (4 %) with nausea. Hematological changes with grade 3 occurred in three cases (12 %) with hemoglobin decrease, in five cases (25 %) as leukopenia, and in one case (4 %) with thrombocytopenia. The mean dose for liver was 16 Gy and the percentage volume exceeding 30 Gy (V30) was 21 %. Mean dose for right and left kidney was 9 and 13 Gy, respectively, and V20 was 9 % and 13 %, respectively. Heart received a median dose of 15 Gy and V40 was 17 %. The mean dose to the bowel was 11 Gy and V40 was 6 %. Spinal cord had at maximum 33 Gy in median. Specifics of dose distribution, including the coverage, for the target region were as follows: minimum was 33 Gy, maximum 48.6 Gy, and mean dose 44.6 Gy. The prescribed dose (45 Gy) covered 99 % and 95 % of planning target volume (OTV) in 66 % and 92 % of cases, respectively. Median PTV was 15.77 ml (range, 805–3,604 ml).

Conclusions

The data support the practical feasibility of IMRT in adjuvant treatment in high-risk gastric cancer in the postoperative setting as a proof of principle. Acute toxicity has been tolerable.     

Radiotherapy alone versus radiochemotherapy in patients with stage IIIA adenocarcinoma (ADC) of the lung

Purpose

To evaluate the outcome of radiotherapy (RT) versus radiochemotherapy (RT-CHT) in patients with locally advanced (stage III) inoperable adenocarcinoma of the lung.

Patients and methods

146 patients with these characteristics were among 600 patients enrolled into five prospective trials and were treated with either hyperfractionated (Hfx) RT (64.8 and 69.6 Gy using 1.2 Gy bid) alone (n = 33) or with Hfx RT (64.8 and 69.6 Gy using 1.2 Gy bid and 67.6 Gy using 1.3 Gy bid) and concurrent carboplatin–etoposide or paclitaxel–carboplatin (n = 113).

Results

The median times and 5-year overall survival (OS), local progression-free survival (LPFS) and the distant metastasis-free survival (DMFS) rates for all 146 patients were 17, 20 and 20 months, respectively, and 15, 26 and 33, respectively. RT-CHT was superior to RT alone in terms of both OS (MST 19 vs. 12 months, respectively, 5-year OS 18 vs. 6 %, respectively; p = 0.003) and LPFS (MTLP 21 vs. 15 months, respectively, 5-year LPFS 28 vs. 0 %; p = 0.06), but not the DMFS (p = 0.43). In all 146 patients, the most frequent acute high-grade toxicity was esophageal, bronchopulmonary and hematological (each 12 %), while the most frequent late high-grade toxicity was bronchopulmonary (4 %) and esophageal (3 %). RT-CHT caused significantly more frequent acute high-grade (>3) esophageal (15 %), and hematological (15 %), while late high-grade toxicity was similar between RT and RT-CHT groups of patients.

Conclusion

RT-CHT achieved excellent results (MST 19 months, 5-year survival 18 %) in this patient population accompanied with low toxicity, comparing favorably to results of other similar studies.     

Trastuzumab and Hypofractionated Whole Breast Radiotherapy: A Victorious Combination?

Introduction

The purpose of this study was to examine the impact of trastuzumab on acute skin and cardiac toxicity in patients with breast cancer treated with chemotherapy with or without trastuzumab and adjuvant whole breast hypofractionated radiotherapy (hypo-RT).

Feasibility of extended-field irradiation and intracavitary brachytherapy combined with weekly cisplatin chemosensitization for IB2–IIIB cervical cancer with positive paraaortic or high common iliac lymph nodes: a retrospective review

Background

The aim of this retrospective study was to investigate the feasibility of primary treatment with extended-field irradiation and weekly cisplatin (extended-field concurrent chemoradiotherapy, EFCCRT) as initial therapy in patients with International Federation of Gynecology and Obstetrics IB1 to IIIB cervical cancer with paraaortic or high common iliac lymph node metastases.

Methods

Participants comprised patients with confirmed cervical cancer, showing paraaortic or high common iliac lymph node metastases on diagnostic imaging, treated with EFCCRT. Total external radiation doses were 50.4 Gy to the whole pelvis and 45.0 Gy to the lumbar paraaortic region. High-dose-rate intracavitary brachytherapy was performed to deliver a total dose of 18–24 Gy in 6-Gy fractions prescribed at point A. Weekly cisplatin (30–40 mg/m²) was given concurrently with radiotherapy.

Results

Twenty-four patients were treated. Median follow-up interval was 34 months. The dose of cisplatin was 30 mg/m² in 2 cases, 35 mg/m² in 8 cases, and 40 mg/m² in 14 cases. Twenty-two cases (92 %) received more than 160 mg/m² cisplatin. Ten cases (42 %) experienced acute grade 3/4 hematological toxicity, and 9 cases (38 %) experienced acute grade 3 nonhematological toxicity. No case presented late grade 3/4 toxicity. Three-year progression-free and overall survival rates were 54 % and 72 %, respectively. Eleven cases recurred during follow-up. Sites of recurrence were within the irradiation field in 4 cases, outside the field in 6 cases, and in both fields in 1 case.

Conclusion

EFCCRT and high-dose-rate intracavitary brachytherapy for patients with paraaortic or high common iliac lymph node metastases from cervical cancer is feasible.     

Acute toxicity of image-guided hypofractionated proton therapy for localized prostate cancer

Background

Hypofractionated proton therapy (HFPT) is expected to become an effective treatment approach for localized prostate cancer (PCa). The purpose of this study was to evaluate differences in acute toxicity among patients with localized PCa treated with either conventional fractionated proton therapy (CFPT) or HFPT.

Methods

A total of 526 eligible patients treated with proton therapy between February 2013 and May 2016 in three phase II trials were analyzed. We prescribed 74 gray relative biological effectiveness equivalents [Gy (RBE)]/37 fractions for low-risk patients and 78 Gy (RBE)/39 fractions for intermediate- and high-risk patients in the CFPT group (n = 254) and 60 Gy (RBE)/20 fractions for low-risk and 63 Gy (RBE)/21 fractions for intermediate- and high-risk patients in the HFPT group (n = 272). Patients were evaluated for acute toxicity with the Common Terminology Criteria for Adverse Events, version 4.0, and urinary quality-of-life change using the International Prostate Symptom Score (IPSS).

Results

No grade ≥3 acute toxicity was observed in either group. Among acute genitourinary toxicities, grade 2 rates were 15% (n = 38) in CFPT and 5.9% (n = 16) in HFPT (P ≤ 0.001). The median baseline IPSSs of the CFPT and HFPT groups were 7 (0–29) and 6 (0–31), respectively (P = 0.70). One-month post-treatment scores were 9 (0–32) and 11 (0–32), respectively (P = 0.036), and 6-month post-treatment scores were 7 (0–30) and 7 (0–33), respectively (P = 0.88). There were no significant differences in acute gastrointestinal toxicity between the two groups.

Conclusion

Our results demonstrated the safety of HFPT for localized PCa patients in terms of acute toxicity.

     

Stereotactic ablative radiotherapy delivered by image-guided helical tomotherapy for extracranial oligometastases

Purpose

To investigate the outcomes and risk factors of patients treated with stereotactic ablative radiotherapy (SABR) delivered by image-guided helical tomotherapy (HT) for extracranial oligometastases.

Methods

From August 2006 through July 2011, 42 consecutive patients (median age 69 years [range 16–87]) with oligometastases (≤3) received HT to all known cancer sites (lung, n = 28; liver, n = 12; adrenal, n = 2). Prognostic factors were assessed by Cox’s proportional hazards regression analysis.

Results

A total of 60 lesions were treated with hypofractionated HT (median dose 39 Gy [range 36–72.5]; median dose per fraction 12 Gy [range 5–20]). Complete or partial response was observed in 40 (54 %) patients. With a median follow-up period of 15 months, 1- and 2-year overall survival (OS) was 84 and 63 %, respectively; and 1- and 2-year local control (LC) was 92 and 86 %, respectively. Four patients had pneumonitis Grade ≥2 and two patients had lower gastrointestinal toxicity Grade ≥2. Only the lack of complete/partial response was associated with higher risk of mortality on univariate (HR = 3.8, P = 0.04) and multivariate (HR = 6.6, P = 0.01) analyses.

Conclusions

SABR delivered by image-guided HT is well tolerated and offers adequate LC with low acute morbidity in patients with extracranial oligometastatic disease. We found that the response to HT was the only predictor for OS.     

Multicenter phase II trial of preoperative chemoradiotherapy with S-1 for locally advanced oral squamous cell carcinoma

Purpose

We evaluated whether preoperative chemotherapy with S-1 and concurrent radiotherapy is feasible and efficacious in the treatment of advanced oral squamous cell carcinoma.

Methods

Participants comprised 39 patients with oral carcinoma (stage III, n = 15; stage IVA, n = 24). All patients received a total radiation dose of 40 Gy, in once-daily 2-Gy fractions, and received S-1 at 65 mg/m²/day for 5 consecutive days, over 4 consecutive weeks with concurrent radiotherapy.

Results

Hematological toxicity was mild and reversible. The most common non-hematological toxicity was grade 3 mucositis, but this was transient and tolerable. Radical surgery was performed for 37 patients, with the remaining 2 patients declining the surgery. Postoperatively, local failure developed in 1 patient, and neck failure in 2 patients. Distant metastases were identified in 4 patients. At a median follow-up of 38.0 months (range 23–88 months), locoregional control, disease-specific survival, and overall survival rates at 3 years were 91.5, 83.8, and 83.8 %, respectively.

Conclusion

Concurrent administration of S-1 and radiotherapy combined with surgery offers a well-tolerated method of successfully treating advanced oral squamous cell carcinoma. The locoregional control rate remains high even at 3 years of follow-up, and no serious adverse effects have been encountered.     

Final results of a phase II single-institutional trial with hyperfractionated radiation therapy (HFX) and four-weekly continuous cisplatin in locally advanced head and neck carcinoma

Background

To evaluate the efficacy and toxicity of hyperfractionated radiation therapy and continuous infusion of cisplatin on weeks 1 and 5 in locally advanced head and neck carcinoma.

Methods

There were 53 patients: 3 (5.7 %) T2 patients, 31 T3 patients (58.4 %), and 19 T4 patients (35.8 %). Forty-one patients (77.4 %) were N-positive. According to the AJCC, 40 (75.4 %) patients had stage IV and the rest stage III. Treatment consisted of hyperfractionated radiation therapy, 120 cGy bid to a dose of 76.8–81.6 Gy, and cisplatin 20 mg/m²/day administered by continuous infusion over 120 h during days 1–5 and 21–25 of radiation therapy.

Results

Tumor response and toxicity There were 40 (75.5 %) complete responses, 6 partial responses (11.3 %), and 5 (9.4 %) non-responses or progression. Two patients were non-evaluable for response due to toxic death. All patients had some acute toxicity grade, the most frequent being mucositis (grade 3–4 in 33 patients) and epithelitis (grade 3–4 in 30 patients). Regarding late toxicity, only 2/24 long-term survivors had tracheostomy, and none of them needed enteral nutrition. Survival and local control With a median follow-up of 66 months, the 5-year overall survival rate for all the series was 49.1 % (95 % CI 58.9–39.3 %) with a median survival duration of 32.83 months. Five-year local control was 68.4 % (95 % CI 81.3–55.5 %).

Conclusions

Hyperfractionated radiation therapy and continuous infusion of cisplatin during weeks 1 and 5 are an active treatment in patients with LAHNC. Nevertheless, new strategies are necessary to increase the local control rates and reduce the incidence of distant metastasis and second tumors.     

Retreatment with radiotherapy for symptomatic bone, brain or visceral metastases

Background

The need for reirradiation in the metastatic disease appears when other modalities of treatment lose their efficacy. The aim of reirradiation in the metastatic disease is mainly palliative to control a particular symptom. However, this theoretical benefit must be confronted against the risk of an undesirable toxicity.

Materials and Methods

Experience with reirradiation for symptomatic bone, brain or visceral metastases are reviewed. Twenty-two patients were found to have a second palliative radiotherapy on the same location. Locatión of metastases were visceral in 5 (23 %) patients, brain in 4 (18 %) patients, spine in 1 (4.5 %) patient and bone metastasis other than spine in 12 (54.5 %) patients. Median dose delivered in the first treatment was 30 Gy (range 20–30 Gy) and 20 Gy for the second treatment (range 6–32.4 Gy).

Results

A good symptomatic response after first irradiation (complete response or disappearance of >50 % of symptoms) was reached in 21 (95.5 %) of the 22 patients analyzed. After second irradiation, 82 % (18 patients) achieved a good response, 3 (14 %) patients had a moderate response (relief of symptoms <50 %) whereas no response was observed in 1 (4 %) patient. Acute toxicity was limited to grade 1–2 proctitis in 2 and 3 patients after the first and second irradiation, respectively. No cases of late toxicity after the first or second irradiation were recorded.

Conclusion

A second treatment with palliative radiotherapy is feasible and well tolerated and offers the possibility of symptomatic relief in a high percentage of patients with symptomatic metastases.     

Competing causes of death in patients with locoregionally advanced head and neck cancer treated with concomitant boost radiation plus concurrent weekly cisplatin

Background

This study analyzes the morbidity and the contribution of different causes of death to the outcome of patients with locally advanced head and- neck cancer after weekly cisplatin plus concomitant boost accelerated radiation treated in our center.

Materials and methods

Ninety-four patients with locally advanced head and neck carcinoma were included in this phase II trial consisting of concomitant boost radiation plus concurrent weekly cisplatin. The 43 patients treated in our centered with long-term follow-up were analyzed. Patients received radiotherapy with a concomitant boost scheme (1.8 Gy on days 1–40 and 1.5 Gy boost on days 25–40 with a total dose of 72 Gy) and concurrent cisplatin, 40 mg/m² weekly, for the first 4 weeks.

Results

Most patients (93 %) received both radiation and complete chemotherapy according to protocol. Severe late toxicity presented were subcutaneous (5 %), larynx (2 %) and esophagous (5 %). Grade I–II late toxicity included mainly xerostomy (30 %), skin (16 %) and mucosal (16 %) toxicity. With a median follow-up of 95 months (9–135), the median overall survival and progression-free survival were 26 and 19 months, respectively (95 % CI 1–52; and 95 % CI 0–45); 60 % of the patients died because of head and neck cancer and 12 % of a second neoplasm, while 27 % of non-cancer patients died.

Conclusions

Patients with locoregionally advanced head and neck cancer treated with concomitant boost accelerated radiation plus chemotherapy show significant risks of mortality from causes other than disease progression.     

Phase II Trial of Concomitant Neoadjuvant Chemotherapy with Oxaliplatin and Capecitabine and Intensity-Modulated Radiotherapy (IMRT) in Rectal Cancer

Introduction and Purpose

The purposes of this study are to evaluate the activity and safety of preoperative intensity-modulated radiotherapy and concurrent capecitabine and oxaliplatin (Xelox), the accuracy of preoperative magnetic resonance (MRI) for predicting pathologic results, and the correlation between carcinoembryonic antigen (CEA) and the existence of a pathologic complete response (pCR).

Patients and Methods

Twenty-seven patients (pt) with T3/T4N0/N+ rectal cancer were included. Capecitabine was administered at 825 t.i.d. mg/m² the days of the radiotherapy (RT), and oxaliplatin was administered weekly at 50 mg/m². RT was planned to 50.4 Gy. Surgery was scheduled 6 to 8 weeks after completion of Xelox RT. Before the intervention, a pelvic MRI was performed and a CEA level was determined.

Results

After Xelox RT, 7 pt had pCR (26%), 2 pt progression disease, and 18 pt tumor downstaging. Presurgical MRI did not predict the pathological result in 21 pt. Main side effects were diarrhea grade (G) 3 in four pt, hand and foot G1 five Pt and G2 four pt. Paresthesias G1 ten pt, G2 seven pt, and leukopenia six pt G1. Median RT dose was 49.7 Gy (47.5–50.4 Gy). At a mean follow-up of 22.5 months, four pt presented metastatis. Mean pretreatment CEA was 6.8 ng/mL (2.1–17.0). A difference statistically significant when compared pretreatment CEA with presurgical CEA (p?<?0.001) was detected. We found a nadir of <5 ng/mL as significantly associated with pCR (p?=?0.036).

Conclusion

Preoperative chemoradiotherapy with oxaliplatin and capecitabine is safe and well tolerated, and offers an interesting ratio of pCR and of tumor downstaging. Presurgical CEA level should be studied as predictors of pCR.