Combination Of Intensity-modulated Radiation Therapy Research Articles

Impact of different treatment plans on EQD2 for intracavitary brachytherapy of cervical cancer

BackgroundCancer is one of the leading causes of death worldwide. According to GLOBOCAN estimates, there were 341,831 deaths from cervical cancer in 185 countries in 2020. The aim of this study was to compare equieffective dose (EQD2) at 2 Gy per fraction by using dose volume histograms (DVHs) derived from external beam radiotherapy (EBRT) and high-dose rate brachytherapy (HDR-BRT) treatment plans used in cervical cancer radiotherapy.MethodsFifteen patients with stage IIB-IIIB cervical cancer were included in this retrospective study. Treatment with three-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT) was planned for all patients in 28 fractions, with a total of 50.4 Gy to be delivered to the whole pelvic region. After EBRT, manual optimization (MO) or inverse optimization (IO) HDR-BRT plans were created in 4 fractions with a total of 28 Gy. The plans obtained were grouped as IMRT + IO, IMRT + MO, 3DCRT + IO, and 3DCRT + MO by calculating EQD2s among these plans. D90, D95, and D98 values were compared in all plans for CTVHR total EQD2. In addition, EQD2 values ​for critical organs at risk (OARs) such as rectum, bladder, small intestine, and sigmoid were compared in all plans for volumes of 2 cm3, 1 cm3, and 0.1 cm3, respectively.ResultsThere was no significant difference between the treatment groups in terms of CTVHR D90 and CTVIR D90 values; However, CTVHR D95 (p = 0.000) and CTVHR D98 (p = 0.000) values ​were found to be better in IMRT + IO technique. The IMRT + IO technique provided better protection for 2 cm3, 1 cm3, and 0.1 cm3 volumes of OARs compared to other techniques.ConclusionsConsidering all parameters such as CTVHR, CTVIR, rectum, bladder, small intestine, and sigmoid, combination of IMRT + IO treatment option was found to be significantly superior in total EQD2 calculations compared to other plans.

High precision radiotherapy including intensity-modulated radiation therapy and pulsed-dose-rate brachytherapy for cervical cancer: a retrospective monoinstitutional study.

PurposeTo analyse the survival outcomes and toxicity profile of patients treated with pulsed-dose-rate (PDR) brachytherapy (BT) after intensity-modulated radiation therapy (IMRT) for uterine cervical cancer in a single institution.Material and methodsBetween March 2011 and December 2014, 50 patients with histologically proven stages IB1-IVB cervical cancer were treated with IMRT followed by PDR-BT boost. Radiation treatment consisted of IMRT to pelvic with or without paraaortic lymph nodes to a total dose of 45-50.4 Gy. Weekly concomitant chemotherapy was administered to 45 patients. PDR-BT boost was delivered with a median dose of 30 Gy to the high-risk clinical target volume (HR-CTV) after a median time of 14 days since IMRT. Acute and late toxicity were evaluated by Radiation Therapy Oncology Group (RTOG) – European Organization for Research and Treatment of Cancer (EORTC) scoring criteria and Subjective Objective Management Analytic-Late Effects of Normal Tissues (SOMA-LENT) criteria.ResultsTwo patients had tumour persistence at 6 months after the end of BT. After a median follow-up of 33 months, 6 distant metastases with or without regional relapse were observed. The 1- and 5-year progression-free survival was 83% (95% CI: 69-91%) and 76% (95% CI: 61-86%), whereas the 3- and 5-year overall survival was 91% (95% CI: 78-97%) and 76% (95% CI: 56-88%), respectively. Urinary and rectal toxicity higher than grade 2 was observed in 6.3% and 17% of patients, respectively. Five patients (10.6%) had grade 4 gastrointestinal toxicity requiring colostomy.ConclusionsOur study confirms that the combination of IMRT and PDR-BT can be considered an effective treatment for cervical cancer, ensuring high local control, despite the high percentage of locally advanced disease.

Intensity-Modulated Radiation Therapy with Stereotactic Body Radiation Therapy Boost for Unfavorable Prostate Cancer: The Georgetown University Experience

Stereotactic body radiation therapy (SBRT) is emerging as a minimally invasive alternative to brachytherapy to deliver highly conformal, dose--escalated radiation therapy (RT) to the prostate. SBRT alone may not adequately cover the tumor extensions outside the prostate commonly seen in unfavorable prostate cancer. External beam radiation therapy (EBRT) with high dose rate brachytherapy boost is a proven effective therapy for unfavorable prostate cancer. This study reports on early prostate-specific antigen and prostate cancer-specific quality of life (QOL) outcomes in a cohort of unfavorable patients treated with intensity-modulated radiation therapy (IMRT) and SBRT boost. Prostate cancer patients treated with SBRT (19.5 Gy in three fractions) followed by fiducial-guided IMRT (45-50.4 Gy) from March 2008 to September 2012 were included in this retrospective review of prospectively collected data. Biochemical failure was assessed using the Phoenix definition. Patients completed the expanded prostate cancer index composite (EPIC)-26 at baseline, 1 month after the completion of RT, every 3 months for the first year, then every 6 months for a minimum of 2 years. One hundred eight patients (4 low-, 45 intermediate-, and 59 high-risk) with median age of 74 years completed treatment, with median follow-up of 4.4 years. Sixty-four percent of the patients received androgen deprivation therapy prior to the initiation of RT. The 3-year actuarial biochemical control rates were 100 and 89.8% for intermediate- and high-risk patients, respectively. At the initiation of RT, 9 and 5% of men felt their urinary and bowel function was a moderate to big problem, respectively. Mean EPIC urinary and bowel function and bother scores exhibited transient declines, with subsequent return to near baseline. At 2 years posttreatment, 13.7 and 5% of men felt their urinary and bowel function was a moderate to big problem, respectively. At 3-year follow-up, biochemical control was favorable. Acute urinary and bowel symptoms were comparable to conventionally fractionated IMRT and brachytherapy. Patients recovered to near their baseline urinary and bowel function by 2 years posttreatment. A combination of IMRT with SBRT boost is well tolerated with minimal impact on prostate cancer-specific QOL.

Sensorineural Hearing Loss after Combined Intensity Modulated Radiation Therapy and Cisplatin-Based Chemotherapy for Nasopharyngeal Carcinoma

PURPOSE: The incidence of sensorineural hearing loss (SNHL) after treatment with combination of intensity-modulated radiation therapy (IMRT) and cisplatin-based chemotherapy in nasopharyngeal carcinoma (NPC) patients was evaluated, and relationships of SNHL with host factors, treatment-related factors, and radiation dosimetric parameters were investigated. METHODS: Fifty-one NPC patients treated with IMRT from 2004 to 2009 were analyzed. All patients received neoadjuvant, concurrent, or adjuvant use of cisplatin. Pure tone audiometry was performed during the follow-up period with a median time of 60months, ranging from 28 to 84months. Correlation of SNHL at low frequencies (pure tone average, 0.5-2kHz) with a series of factors was analyzed. RESULTS: Among 102 ears, 12.7% had low-frequency SNHL and 42.2% had high-frequency (4kHz) SNHL. The incidence of low-frequency SNHL was greater in patients with age>40, with T-stage 4, or who received cumulative cisplatin dose (CCD)>200mg/m2 (P=.034, .011, and .003, respectively) and in ears with secretory otitis media (SOM) (P=.002). Several dosimetric parameters were found to be correlated with SNHL. Univariate analysis showed that the minimum radiation dose to 0.1ml highest dose volume (D0.1ml) of the cochlea was the best radiation-related predictive parameter. Multivariate analysis indicated that CCD, SOM, and D0.1ml of cochlea (P=.035, .012, and .022, respectively) were the factors associated with SNHL. CONCLUSION: For NPC patients treated with IMRT and chemotherapy, the incidence of treatment-related SNHL was associated with CCD, D0.1ml of cochlea, and SOM.

G14 - Intensity-modulated radiotherapy and cetuximab for frail patients with loco-regionally advanced head and neck cancer

Background: The combination of radiotherapy (RT) and concomitant cetuximab demonstrated to be superior to RT alone in loco-regionally advanced squamous cell head and neck cancer (SCHNC). The benefit in terms of response rate, progressions-free survival (PFS) and overall survival (OS) has been obtained without increased toxicity. The objective of this study was to evaluate the clinical impact of such approach in frail patients. Methods: From january 2010 to december 2014 15 patients affected by stage III-IV SCHNC (oral cavity, oropharynx, and hypopharynx) not candidate to surgery or chemoradiation according to severe comorbidities or age (> 80 years) were treated with a combination of Intensity-Modulated RT (IMRT) and cetuximab with curative intent. Cetuximab was administered starting one week before IMRT at a loading dose of 400 mg/m2 i.v. followed by 250 mg/m2 i.v. weekly for a total of 8 infusions. Results: In this series the male/female ratio was 1.5 and the median age was 79 years. All patients but one completed IMRT along with 8 cycles of concomitant cetuximab whose median dose intensity was 95%. A complete response was achieved in 11 of 15 patients (73.3%). Three patients had residual nodal disease and underwent salvage neck dissection. Seven patients (46.7%) had loco-regional relapse and five of them developed distant metastases. With a median follow up of 58 months, the duration of locoregional control was 21 months (range, 1-59), median PFS was 16 months and median OS 34 months. Four patients (26.7%) were still alive at five years. Grade 3/4 adverse events occurred in 53.3% of cases, mostly oral mucositis and skin rash. With a careful pre-medication consisting of anti-histamine and steroidal drugs no infusional reactions were documented. One toxic death was registered in a 85-year old woman who died during IMRT as a consequence of severe sepsis. Conclusions: Cetuximab plus definitive IMRT is a feasible and effective treatment for loco-regionally advanced SCHNC. Even in frail patients it can provide good clinical outcomes along with an accettable toxicity profile. This combination allows a chance of cure for a subset of patients not suitable for chemotherapy or major surgery. The results in terms of PFS and OS are clearly inferior if compared to a standard patient population, nonetheless adding cetuximab to IMRT offer some chance of long survivorship to patients in poor clinical conditions, without dramatically altering their quality of life.

A phase II study of radiation therapy (RT), paclitaxel poliglumex (PPX), and cetuximab (C) in locally advanced head and neck cancer (LA-HNC).

6059 Background: RT + cisplatin in LA-HNC showed a survival benefit over RT alone, but with significant toxicity. Addition of C to RT demonstrated survival benefit without increased RT-related toxicity. PPX consists of paclitaxel linked to a biodegradable, water-soluble polymer of glutamic acid. PPX has a radiation enhancement factor of ≈8 in a radiocurability murine model. This study addresses the combined use of intensity modulated RT (IMRT), PPX, and C in patients with LA-HNC. Methods: Eligible patients had untreated stage III/ IV squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, larynx, or unknown primary, ECOG PS 0-1, and adequate bone marrow function. Patients received C 400 mg/m2 day 1 and 250 mg/m2 weekly for 7 weeks. PPX was administered at 40 mg/m² weekly for 7 weeks. IMRT began on day 8 consisting of 69.96 Gy delivered in 2.12 Gy daily. Results: 38 patients with LA-HNC are included in this report and evaluable for response. 24 (63%) had CR and 14 (37%) had PR. HPV status is 21+, 11- and 8 unknown. Pre-therapy, 36 patients had nodal disease, 9 underwent neck dissection post-treatment and 1/ 9 patients had microscopic involvement by cancer. Locoregional tumor control occurred in 36/38 (95%) patients with two patients developing locoregional recurrence after completion of therapy. Two patients have died from metastatic disease and two patients are alive with distant metastases. Two additional deaths were unrelated to therapy (sudden cardiac death and COPD exacerbation with respiratory failure). The majority of adverse events (AEs) were grade 1/2 and consistent with known toxicities of individual agents. The most common grade 3 AEs were mucositis (n=28), radiation dermatitis (n=15), dehydration (n=8) and cetuximab rash (n=9). The median overall survival and progression free survival have not been reached. Updated numbers will be presented. Overall survival rate is 34/38 (89%) by intent-to-treat analysis, with a median follow up of 13 months. Conclusions: The combination of IMRT, PPX, and C is tolerable and shows promising clinical activity in patients with LA-HNC. An expansion cohort of HPV negative patients on this protocol is in progress. Clinical trial information: NCT00660218.

Immune-maximizing (IMAX) therapy for cancer: Combination of dendritic cell vaccine and intensity-modulated radiation

A dendritic cell (DC)-based vaccine was combined with intensity-modulated radiotherapy (IMRT) or other conformal radiotherapy (RT), assuming minimal immunosuppression by such RT modalities. In this study, the outcomes in the first 40 patients are presented. The patients had recurrent, metastatic or locally advanced tumors. Nine had previously undergone full-course RT. Peripheral blood mononuclear cells obtained by leukapheresis were cultured with granulocyte-macrophage colony-stimulating factor, interleukin-4, OK-432 and prostaglandin E2 to generate DCs, which were pulsed with autologous tumor lysates or tumor-specific peptides, such as WT1. IMRT using tomotherapy, stereotactic irradiation or 3-dimensional conformal RT (3DCRT) was initially administered. The standard dose was 30 and 60 Gy in patients with and without previous RT, respectively. Every other week thereafter, up to a total of 7 times, DC vaccines were injected directly into the tumor (n=15) or administered intradermally when DCs were pulsed with tumor lysates or peptides. The tumor response was evaluated according to the response evaluation criteria in solid tumors (RECIST). RT and DC vaccines were well tolerated and there were no major complications. Three patients were not able to complete the planned DC therapy due to disease progression. For the 31 patients receiving full-dose RT, the response rate was 61% and for the 9 patients who had previously received RT, the response rate was 55%. In 9 patients, the tumor response outside the RT target volume was evaluable: 22% had a partial response (PR), 33% had stable disease (SD) and 44% had progressive disease (PD). In conclusion, a combination of IMRT (or 3DCRT) and DC vaccine is feasible and requires further investigation.

A phase I/II study of radiation therapy, paclitaxel poliglumex, and cetuximab in locally advanced head and neck cancer.

e16047 Background: In patients with locally advanced head and neck cancer (LA-HNC), radiotherapy (RT) + cisplatin showed survival benefit over RT alone, but with significant toxicity. The addition of cetuximab to RT demonstrated survival benefit without increased RT-related toxicity. Paclitaxel poliglumex (PPX) is a novel conjugate consisting of paclitaxel linked to a biodegradable, water-soluble polymer of glutamic acid. PPX has a radiation enhancement factor of ≈8 and improved curability in a murine carcinoma model. In a phase I study of PPX + RT in esophageal cancer, no dose-limiting toxicities (DLTs) occurred at PPX doses up to 70 mg/m2/week and an encouraging rate of pathological CRs was observed. This phase I/II study addresses the combined use of intensity modulated RT (IMRT), PPX, and cetuximab in patients with LA-HNC. Methods: Eligible patients had untreated stage III or IV squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx; ECOG PS 0-1; and adequate bone marrow function. In the phase I portion, patients received cetuximab 400 mg/m2 day 1 and 250 mg/m2 days 8, 15, 22, 29, 36, 43, and 50. PPX was administered at 40 mg/m2 days 8, 15, 22, 29, 36, 43, and 50 for Cohort 1 (n = 3) then escalated or decreased for Cohorts 2-5 (3 patients each) until the maximum tolerated dose (MTD) was established. IMRT began on day 8 and consisted of 69.96 Gy delivered in 2.12 Gy daily fractions. In the phase II portion, patients received PPX at the MTD + cetuximab and IMRT at the phase I dose and schedule. Results: In total, 14 patients were treated (9 phase I, 5 phase II). The PPX MTD was determined to be 40 mg/m2. The majority of adverse events (AEs) were grade 1/2 and consistent with known toxicities of individual agents. The most common grade 3 AEs were mucositis (n = 8), radiation dermatitis (n = 4), and cetuximab rash (n = 3). Of 13 patients evaluable for response, 9 had CR and 4 had PR. After a median 17-month follow up, the local control rate was 11/11 and the median survival was 20 months. Two patients with stage IVC disease were excluded for local control and survival analysis. Conclusions: The combination of IMRT, PPX, and cetuximab is tolerable and shows promising clinical activity in patients with LA-HNC.

Phase I/II trial of single-fraction high-dose-rate brachytherapy–boosted hypofractionated intensity-modulated radiation therapy for localized adenocarcinoma of the prostate

PurposeA Phase I/II protocol was conducted to examine the toxicity and efficacy of the combination of intensity-modulated radiation therapy (IMRT) with a single-fraction high-dose-rate (HDR) brachytherapy implant. Methods and MaterialsFrom 2001 through 2006, 26 consecutive patients were treated on the trial. The primary objective was to demonstrate a high rate of completion without experiencing a treatment-limiting toxicity. Eligibility was limited to patients with T stage ≤2b, prostate-specific antigen (PSA) ≤20, and Gleason score ≤7. Treatment began with a single HDR fraction of 6Gy to the entire prostate and 9Gy to the peripheral zone, followed by IMRT optimized to deliver in 28 fractions with a normalized total dose of 70Gy. Patients received 50.4Gy to the pelvic lymph node. The prostate dose (IMRT and HDR) resulted in an average biologic equivalent dose >128Gy (α/β=3). Patients whose pretreatment PSA was ≥10ng/mL, Gleason score 7, or stage ≥T2b received short-term androgen ablation. ResultsMedian followup was 53 months (9–68 months). There were no biochemical failures by either the American Society of Therapeutic Radiology and Oncology or the Phoenix definitions. The median nadir PSA was 0.32ng/mL. All the 26 patients completed the treatment as prescribed. The rate of Grade 3 late genitourinary toxicity was 3.8% consisting of a urethral stricture. There was no other Grade 3 or 4 genitourinary or gastrointestinal toxicities. ConclusionsSingle-fraction HDR-boosted IMRT is a safe effective method of dose escalation for localized prostate cancer.

Combination of intensity-modulated radiation therapy (IMRT) and a heavy ion (C12) boost for subtotal resected or inoperable adenoid cystic carcinomas (ACCs) of the head and neck region.

e16010 Background: Adenoid cystic carcinomas (ACC's) are rare salivary gland tumors. Conventional RT treatment results are still not satisfactory due to relative radioresistance of these tumors. Mo...

Are Current IMRT Plans Superior to 3D Conformal Therapy for Prostate Cancer? A Dosimetric Comparison

Historically, dose escalation in prostate cancer has been limited by normal tissue toxicity, primarily in the rectum and to a lesser degree in the bladder. The introduction of CT based 3D conformal radiation therapy (3DCRT) with blocks or multileaf collimators (MLCs) provided for a significant improvement in dose conformality. With the subsequent development and introduction of intensity modulated radiation therapy (IMRT), it is now possible to further conform the delivered dose to the outlined planning target volume (PTV), while at the same time maximize the sparing of the critical structures. This has enabled attempts to escalate the prescribed dose with the goal of not increasing toxicity. With the combination of IMRT and the inverse treatment planning algorithms currently available, dose constraints to critical structures such as the rectum and bladder can be directly included in the optimization calculation of the optimal solution. As of today, there are no standard criteria for absolute dose limits to critical structures, nor is there even a customary system to describe these criteria in the treatment of the prostate cancer. The Radiation Therapy Oncology Group (RTOG) has used data from past published works in an effort to define some of the prescription parameters for 3D-CRT and IMRT treatments in prostate cancer. Early investigations, based on results from a randomized study at MD Anderson Hospital, showed the benefits of higher radiation doses to the prostate. Evaluating toxicity, they found that if no more than 25% of the rectum received 7000 cGy, the risk of rectal bleeding decreased from 46% to 16%. Those have been the parameters for subsequent studies, including the current high priority study RTOG 0415. Some cancer centers have elected to create their own criteria, which is the case at Fox Chase Cancer Center (FCCC) in Philadelphia, PA. The strict criteria they use was also reviewed in this study, to compare with the 3D and RTOG 0415 criteria. Given the significant difference in complexity between the planning and delivery of a 3DCRTplan as compared to an IMRT treatment, the scope of this present study is to investigate whether there are dosimetric advantages of employing IMRT instead of 3D-CRT, utilizing the current constraints as described in RTOG 0415. Methods and Materials

Comparison of two treatment approaches for prostate cancer: intensity‐modulated radiation therapy combined with seed‐implant brachytherapy or seed‐implant brachytherapy alone

The purpose of the present study was to assess the results of two different treatment approaches for clinically localized prostate cancer: intensity‐modulated radiation therapy (IMRT) followed by I125 seed‐implant brachytherapy and I125 seed‐implant brachytherapy alone. We studied our 30 most recent consecutive patients. The sample population consisted of 15 cases treated with IMRT (50.4 Gy) followed by I125 seed‐implant boost (95 Gy), and 15 cases treated with I125 seed implant only (144 Gy). We analyzed established dosimetric indices and various clinical parameters. In addition, we also evaluated and compared the acute urinary morbidities of the two treatment approaches, as assessed by the international prostate symptom score (IPSS). In our series, acute urinary morbidity was slightly increased with IMRT followed by I125 seed‐implant brachytherapy as compared with I125 seed‐implant brachytherapy alone. In addition, we observed no statistically significant correlation between the IPSS and the maximum or mean urethral dose. The combination of IMRT and seed‐implant brachytherapy presents an alternative opportunity to treat clinically localized prostate cancer. The full potential of the procedure needs to be further investigated.PACS number: 87.53.Tf

Use of stereotactic intensity-modulated radiotherapy in thyroid-related ophthalmopathy

✓ Thyroid-related ophthalmopathy (TRO), a debilitating condition involving a range of visual and orbital symptoms, occurs in up to 40% of patients with Graves disease. The goals of treatment include correcting thyroid dysfunction, relieving ocular pain, preserving vision, and improving cosmetic appearance. Options for therapy include symptomatic treatment, glucocorticoid medication, radiation therapy, and surgery. Traditional radiation treatment uses small opposed bilateral fields consisting of retrobulbar volumes and customized blocks to shield periorbital structures. The combination of intensity-modulated radiotherapy (IMRT) and stereotactic technology facilitates the administration of radiation to patients suffering from TRO and provides greater safety and efficacy than traditional treatment. The authors present the case of a patient with severe TRO whose symptoms resolved rapidly after treatment with stereotactic IMRT. The outcome in this case supports stereotactic IMRT as an effective treatment option for patients with TRO who also undergo radiation therapy.

Use of stereotactic intensity-modulated radiotherapy in thyroid-related ophthalmopathy

✓ Thyroid-related ophthalmopathy (TRO), a debilitating condition involving a range of visual and orbital symptoms, occurs in up to 40% of patients with Graves disease. The goals of treatment include correcting thyroid dysfunction, relieving ocular pain, preserving vision, and improving cosmetic appearance. Options for therapy include symptomatic treatment, glucocorticoid medication, radiation therapy, and surgery. Traditional radiation treatment uses small opposed bilateral fields consisting of retrobulbar volumes and customized blocks to shield periorbital structures. The combination of intensity-modulated radiotherapy (IMRT) and stereotactic technology facilitates the administration of radiation to patients suffering from TRO and provides greater safety and efficacy than traditional treatment. The authors present the case of a patient with severe TRO whose symptoms resolved rapidly after treatment with stereotactic IMRT. The outcome in this case supports stereotactic IMRT as an effective treatment option for patients with TRO who also undergo radiation therapy.