Conventional Fractionation Schedules Research Articles

Complication Rates After Mastectomy and Reconstruction in Breast Cancer Patients Treated with Hypofractionated Radiation Therapy Compared to Conventional Fractionation: A Single Institutional Analysis.

Radiation therapy plays an important role in the treatment of localized breast cancer. Hypofractionated (HF) radiation therapy has emerged as a promising alternative to conventional fractionation (CF) schedules, offering comparable efficacy with reduced treatment duration and costs. However, concerns remain regarding its safety and rate of toxicity, particularly in patients undergoing mastectomy with breast reconstruction. This study aimed to assess the implant-related complications in breast cancer patients receiving HF post-mastectomy radiation therapy (PMRT) and reconstruction compared to CF PMRT. A retrospective study was conducted on 59 breast cancer patients who underwent mastectomy and breast reconstruction between 2013 and 2021 and received adjuvant PMRT. Patient demographics, treatment characteristics, and implant-related complications were analyzed. Statistical tests including chi-square, Fischer's exact test, and multivariable Cox regression were employed for analysis. Of the 59 patients, 29 received HF PMRT and 30 received CF PMRT. At a median follow-up of 23.4 months, there was no significant difference in major implant-related complications between the two groups (24.1% in HF vs. 33.3% in CF, p = 0.436). Most complications in the HF group occurred within the first two years post-radiation. Age over 40 was identified as a significant predictor for higher implant-related complications (p = 0.029). Our findings indicate that HF PMRT and reconstruction does not increase the risk of major implant-related complications compared to CF PMRT. These results align with the existing literature, supporting the safety of HF radiation in breast cancer patients who underwent mastectomy with reconstruction.

Comparison of Conventional Palliative Radiotherapy Fractionation Schedule with Quad Shot Regimen in Locally Advanced Head and Neck Cancer Patients: A Randomised Clinical Trial

Introduction: Head and Neck Cancer (HNC) accounts for 14.3% of all cancers in India and 4.8% of all cancers worldwide. In India, the most common sites are the lip and oral cavity (>80%), which are more prevalent in men than in women. Histologically, most cases are Squamous Cell Carcinomas (SCC). The majority of patients present with locally advanced stages, where surgery and definitive chemoradiation therapy are not possible and palliative Radiotherapy (RT) is considered a treatment option for better symptomatic relief and improved Quality of Life (QoL). The Quad Shot (QS) palliative regimen has shortened treatment time, reduced toxicity and increased compliance. Aim: To compare the QS regimen administered over two consecutive days versus the Conventional Palliative Regimen in the treatment of locally advanced HNC, in terms of treatment response, acute toxicities and QoL. Materials and Methods: In this prospective randomised clinical trial conducted from May 2023 to July 2024 in the Department of Radiation Oncology at King George's Medical University (KGMU), Lucknow, Uttar Pradesh, India, patients with biopsyproven locally advanced carcinoma of the head and neck were recruited, with a sample size of 50 in each of the study Group B and control Group A arms. Patients in the control arm received 30 Gray (Gy) in 10 fractions, 5 fractions per week over two weeks (Conventional palliative arm). In the study arm, patients received 14 Gy in 4 fractions delivered in two daily sessions, six to eight hours apart, for two consecutive days over three cycles (QS arm). The Response Evaluation Criteria in Solid Tumours (RECIST) Criteria 1.1 was used to assess the tumour response objectively three months post-RT. Health-related QoL was assessed using questionnaires developed by the European Organisation for Research and Treatment of Cancer (EORTC), specifically the EORTC Quality of Life Questionnaire (QLQ). Continuous data were compared using the t-test for nominal data and the Mann-Whitney U test was used otherwise. Results: The mean age was 39.66±12.05 years in Group A and 42.76±11.65 years in Group B. The QS and conventional palliative arms each had 47 and 49 patients recruited, respectively. The QS arm exhibited fewer instances of skin toxicity, with 25 (53.2%) experiencing Grade I and 7 (14.9%) experiencing Grade II toxicity, compared to the conventional palliative arm, where 30 (61.2%) had Grade I and 12 (24.5%) had Grade II toxicity. Mucositis in the QS arm included 22 (46.9%) cases, with 14 (29.7%) classified as Grade I and Grade II, whereas the conventional arm had 12 (24.5%) Grade I cases, 29 (59.5%) Grade II cases and 3 (6.1%) Grade III cases. The treatment response, in terms of partial and stable disease combined, was observed in 61.2% of the conventional arm compared to 78.7% in the QS arm. QoL was reported to be better in the QS regimen post-treatment. Conclusion: Given the total number of patients recruited, the QS arm, with its shorter treatment time, demonstrated better benefits in terms of reduced toxicities and improved treatment response, as well as enhanced QoL compared to the conventional palliative arm.

Hypofractionated vs Conventionally Fractionated Postmastectomy Radiation After Implant-Based Reconstruction

Postmastectomy radiation therapy (PMRT) improves local-regional disease control and patient survival. Hypofractionation (HF) regimens have comparable efficacy and complication rates with improved quality of life compared with conventional fractionation (CF) schedules. However, the use of HF after mastectomy in patients undergoing breast reconstruction has not been prospectively examined. To compare HF and CF PMRT outcomes after implant-based reconstruction. This randomized clinical trial assessed patients 18 years or older undergoing mastectomy and immediate expander or implant reconstruction for breast cancer (Tis, TX, or T1-3) and unilateral PMRT from March 8, 2018, to November 3, 2021 (median [range] follow-up, 40.4 [15.4-63.0] months), at 16 US cancer centers or hospitals. Analyses were conducted between September and December 2023. Patients were randomized 1:1 to HF or CF PMRT. Chest wall doses were 4256 cGy for 16 fractions for HF and 5000 cGy for 25 fractions for CF. Chest wall toxic effects were defined as a grade 3 or higher adverse event. The primary outcome was the change in physical well-being (PWB) domain of the Functional Assessment of Cancer Therapy-Breast (FACT-B) quality-of-life assessment tool at 6 months after starting PMRT, controlling for age. Secondary outcomes included toxic effects and cancer recurrence. Of 400 women (201 in the CF arm and 199 in the HF arm; median [range] age, 47 [23-79] years), 330 patients had PWB scores at baseline and at 6 months. There was no difference in the change in PWB between the study arms (estimate, 0.13; 95% CI, -0.86 to 1.11; P = .80), but there was a significant interaction between age group and study arm (P = .03 for interaction). Patients younger than 45 years had higher 6-month absolute PWB scores if treated with HF rather than CF regimens (23.6 [95% CI, 22.7-24.6] vs 22.0 [95% CI, 20.7-23.3]; P = .047) and reported being less bothered by adverse effects (mean [SD], 3.0 [0.9] in the HF arm and 2.6 [1.2] in the CF arm; P = .02) or nausea (mean [SD], 3.8 [0.4] in the HF arm and 3.6 [0.8] in the CF arm; P = .04). In the as-treated cohort, there were 23 distant (11 in the HF arm and 12 in the CF arm) and 2 local-regional (1 in the HF arm and 1 in the CF arm) recurrences. Chest wall toxic effects occurred in 39 patients (20 in the HF arm and 19 in the CF arm) at a median (IQR) of 7.2 (1.8-12.9) months. Fractionation was not associated with chest wall toxic effects on multivariate analysis (HF arm: hazard ratio, 1.02; 95% CI, 0.52-2.00; P = .95). Fewer patients undergoing HF vs CF regimens had a treatment break (5 [2.7%] vs 15 [7.7%]; P = .03) or required unpaid time off from work (17 [8.5%] vs 34 [16.9%]; P = .02). In this randomized clinical trial, the HF regimen did not significantly improve change in PWB compared with the CF regimen. These data add to the increasing experience with HF PMRT in patients with implant-based reconstruction. ClinicalTrials.gov Identifier: NCT03422003.

Targeting the Tumor Vascular Supply to Enhance Radiation Therapy Administered in Single or Clinically Relevant Fractionated Schedules.

This pre-clinical study was designed to demonstrate how vascular disrupting agents (VDAs) should be administered, either alone or when combined with radiation in clinically relevant fractionated radiation schedules, for the optimal anti-tumor effect. CDF1 mice, implanted in the right rear foot with a 200 mm3 murine C3H mammary carcinoma, were injected with various doses of the most potent VDA drug, combretastatin A-1 phosphate (CA1P), under different schedules. Tumors were also locally irradiated with single-dose, or stereotactic (3 × 5-20 Gy) or conventional (30 × 2 Gy) fractionation schedules. Tumor growth and control were the endpoints used. Untreated tumors had a tumor growth time (TGT5; time to grow to 5 times the original treatment volume) of around 6 days. This increased with increasing drug doses (5-100 mg/kg). However, with single-drug treatments, the maximum TGT5 was only 10 days, yet this increased to 19 days when injecting the drug on a weekly basis or as three treatments in one week. CA1P enhanced radiation response regardless of the schedule or interval between the VDA and radiation. There was a dose-dependent increase in radiation response when the combined with a single, stereotactic, or conventional fractionated irradiation, but these enhancements plateaued at around a drug dose of 25 mg/kg. This pre-clinical study demonstrated how VDAs should be combined with clinically applicable fractionated radiation schedules for the optimal anti-tumor effect, thus suggesting the necessary pre-clinical testing required to ultimately establish VDAs in clinical practice.

Concurrent chemoradiation with low-dose and long-duration weekly infusion of gemcitabine in unresectable squamous cell carcinoma of head and neck (SCCHN).

Concurrent chemoradiotherapy now represents the standard of care in locally advanced unresectable squamous cell carcinoma of the head and neck, and the administration of cisplatin in triweekly or weekly schedules is the most commonly used chemotherapeutic agent. However, the chemotherapeutic agent and its scheduling with radiation is still an area of investigation with safer toxicity profile and better response rates. Gemcitabine is a potent radiosensitizer, and non-cytotoxic concentration results in decreased systemic toxicity while maintaining radiosensitization properties. Furthermore, data are emerging for low-dose and long-duration infusion where this strategy is found to be effective and a safe alternative to standard brief infusion. Based on these two strategies, that is, non-cytotoxic concentration with long duration, we have explored the unique possibility of further lowering the toxicity profile without compromising the efficacy. Eligible patients of locally advanced unresectable squamous cell carcinoma of the head and neck underwent radiation treatment with concurrent gemcitabine. A total dose of 70 Gy in 35 fractions over a period of seven weeks with conventional fractionation schedule was delivered with cord off after 44 Gy. Concurrent gemcitabine was administered intravenously for over two hours once a week, 1-2 h before radiation and for seven consecutive weeks at 50 mg/m2. Fifty-two patients was enrolled in this study, out of which 41 completed the treatment. Fifty-nine percent completed treatment within seven weeks. Sixty-four percent were found to have received more than five cycles. Mean follow-up of patients was found to be 4.9 months. Sixty-eight percent had complete response. Stage III patients achieved more complete response compared to stage IV. There was no site-wise difference in achieving complete response. Patients who have received less than five chemo cycles or completed the treatment in more than seven weeks had less complete response. Sixty-one percent had severe mucositis while 39% developed mild/moderate mucositis. Considering skin toxicity, 80% were found to have mild/moderate skin toxicity, while only 20% suffered from severe grades of skin toxicity. Gemcitabine in low-dose and long-duration infusion is a potent radiosensitizer with safer hematological toxicity and manageable local toxicities.

Adjuvant medial versus entire supraclavicular lymph node irradiation in high-risk early breast cancer (SUCLANODE): a protocol for a multicenter, randomized, open-label, phase 3 trial

BackgroundSupraclavicular nodal (SCL) irradiation is commonly used for patients with high-risk breast cancer after breast surgery. The Radiation Therapy Oncology Group (RTOG) and European Society for Radiotherapy and Oncology (ESTRO) breast contouring atlases delineate the medial part of the SCL region, while excluding the posterolateral part. However, recent studies have found that a substantial proportion of SCL failures are located in the posterolateral SCL region, outside of the RTOG/ESTRO-defined SCL target volumes. Consequently, many radiation oncologists advocate for enlarging the SCL irradiation target volume to include both the medial and posterolateral SCL regions. Nevertheless, it remains uncertain whether adding the posterolateral SCL irradiation improves survival outcomes for high-risk breast cancer patients.MethodsThe SUCLANODE trial is an open-label, multicenter, randomized, phase 3 trial comparing the efficacy and adverse events of medial SCL irradiation (M-SCLI group) and medial plus posterolateral SCL irradiation (entire SCL irradiation, E-SCLI group) in high-risk breast cancer patients who underwent breast conserving-surgery or mastectomy. Patients with pathological N2-3b disease following initial surgery, or clinical stage III or pathological N1-3b if receiving neoadjuvant systemic therapy, are eligible and randomly assigned (1:1) to M-SCLI group and E-SCLI group. Stratification is by chemotherapy sequence (neoadjuvant vs. adjuvant), T stage (T3-4 vs. T1-2), N stage (N1-2 vs. N3), and ER status (positive vs. negative). Other radiation volumes are identical in the two arms, including breast/chest wall, undissected axillary lymph node, and internal mammary node. Advanced intensity modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT), or tomotherapy techniques are recommended. Both hypofractionated and conventional fractionation schedules are permitted. The primary end point is invasive disease-free survival, and secondary end points included overall survival, SCL recurrence, local-regional recurrence, distance recurrence, safety outcome, and patient-reported outcomes. The target sample size is 1650 participants.DiscussionThe results of the SUCLANODE trial will provide high-level evidence regarding whether adding posterolateral SCL irradiation to medial SCL target volume provides survival benefit in patients with high-risk breast cancer.Trial registrationClinicalTrials.gov Identifier: NCT05059379. Registered 28 September 2021, https://www.clinicaltrials.gov/ct2/show/NCT05059379.

Comparative evaluation of hypofractionated radiotherapy versus conventionally fractionated radiotherapy for patients with intermediate and high risk prostate cancer.

The purpose of this study was to comparatively evaluate an efficacy and toxicity profile of hypofractionated radiotherapy (67.5 Gy in 25 fractions) to conventionally fractionated radiotherapy (78 Gy in 39 fractions) in prostate cancer patients with intermediate and high-risk disease. From January 2015 to December 2018, 168 patients were randomized to hypofractionated radiation treatment and conventional fractionated radiation treatment schedules of volumetric modulated arc therapy (VMAT) to the prostate and seminal vesicles. All the patients also received androgen deprivation therapy (ADT) and radiation therapy started after ADT. The median (range) follow-up was 51 (31-63) and 53 (33-64) months in the hypofractionated and conventionally fractionated regimes, respectively. The 3-year biochemical no evidence of disease (bNED) rates were 86.9% and 73.8% in the hypofractionated and conventionally fractionated groups, respectively (p = 0.032, significant). The 3-year bNED rates in patients at a high risk [i.e., pretreatment prostate-specific antigen (PSA) > 20 ng/mL, Gleason score ≥ 8, or T ≥ 2 c], were 87.9% and 73.5% (p = 0.007, significant) in the hypofractionated and conventionally fractionated radiotherapy groups, respectively. No statistically significant difference was found for late toxicity between the two groups, with 3-year grade 2 gastrointestinal toxicity rates of 19% and 16.7% and 3-year grade 2 genitourinary toxicity rates of 15.5% and 11.9% in the hypofractionated and conventionally fractionated radiotherapy groups, respectively. Hypofractionated schedule is superior to the conventional fractionation schedule of radiation treatment in terms of bNED in intermediate and high grade prostate cancer patients. Also, the late toxicity is found to be equivalent between the two treatment groups.

Radiation Therapy Dose and Fractionation Schedules for Breast Angiosarcomas: An Analysis of the National Cancer Database

Breast angiosarcoma (AS) is an uncommon malignancy that is either secondary to prior radiation therapy (RT) or can occur in the primary setting in the absence of prior RT. Since these malignancies are rare, there are scant prospective data to guide the optimal use and timing of surgery, chemotherapy and RT. Here, we set to focus on details of RT use for primary AS and secondary AS with a focus on the dose, fractionation and timing of RT relative to surgery using the National Cancer Database (NCDB). We hypothesized that RT use would be more frequent in primary AS compared to secondary AS. In addition, we hypothesized that when RT is used, hyperfractionated schedules and preoperative RT would be more common in secondary AS compared to primary AS.We identified patients with a histologic diagnosis of AS from the NCDB from 2004-2016. Patients that were coded as having a prior malignancy were used as a surrogate to denote secondary AS whereas the rest were classified as primary AS. RT use was defined as conventional fractionation (1.8-2.0 Gy/fraction given daily); hypofractionated (> 2.0 Gy/fraction given daily); accelerated hyperfractionated (≤1.5 Gy/fraction given 2-3 times/day); palliative (total dose≤30 Gy); or unknown (insufficient RT details provided). Comparisons between the primary AS and secondary AS groups were performed using the chi-square test with P < 0.05 considered significant.We identified 1,174 patients with non-metastatic AS: 864 secondary AS, 310 primary AS. Radiation was used in 211 patients (18.0%) and was significantly more common in primary AS compared to secondary AS (36.1% [N = 113] vs. 11.4% [N = 98], P < 0.0001). The majority of patients received conventional fractionation (63.5%, N = 134) followed by unknown schedule (16.1%, N = 34), hyperfractionated RT (10.4%, N = 22), palliative RT (6.6%, N = 14), and hypofractionated RT (3.3%, N = 7). Fewer than 10% of patients (N = 18) received preoperative RT but its use was more common in secondary AS vs. primary AS (13.3% vs. 4.4%, P = 0.02). Accelerated hyperfractionated RT use was also more common in secondary AS vs. primary AS (19.4% vs. 2.7%, P < 0.0001). Fractionation schedules for the 22 patients treated with accelerated hyperfractionation included: 1.5 Gy BID to 45-60 Gy in 11 patients; 1.2 Gy BID to 50.4-60 Gy in 8 patients; 1 Gy TID to 45-60 Gy in 3 patients. An additional boost dose of 7.2-15 Gy was given to 11 of these 22 patients.Radiation use for the treatment of breast AS is uncommon, even for patients with primary AS. When RT is used, conventional fractionation schedules predominate. However, accelerated hyperfractionation is used more frequently in secondary AS with 1.5 Gy BID to doses≥45 Gy as the most common regimen. Preoperative RT is rarely used for AS based on this analysis. The under-utilization of RT and wide variations in RT dose/fractionation schedules emphasize the need for more standardized consensus guidelines for this rare but aggressive malignancy.

A reinforcement learning approach for finding optimal policy of adaptive radiation therapy considering uncertain tumor biological response

Recent studies have shown that a tumor's biological response to radiation varies over time and has a dynamic nature. Dynamic biological features of tumor cells underscore the importance of using fractionation and adapting the treatment plan to tumor volume changes in radiation therapy treatment. Adaptive radiation therapy (ART) is an iterative process to adjust the dose of radiation in response to potential changes during the treatment. One of the key challenges in ART is how to determine the optimal timing of adaptations corresponding to tumor response to radiation. This paper aims to develop an automated treatment planning framework incorporating the biological uncertainties to find the optimal adaptation points to achieve a more effective treatment plan. First, a dynamic tumor-response model is proposed to predict weekly tumor volume regression during the period of radiation therapy treatment based on biological factors. Second, a Reinforcement Learning (RL) framework is developed to find the optimal adaptation points for ART considering the uncertainty in biological factors with the goal of achieving maximum final tumor control while minimizing or maintaining the toxicity level of the organs at risk (OARs) per the decision-maker's preference. Third, a beamlet intensity optimization model is solved using the predicted tumor volume at each adaptation point. The performance of the proposed RT treatment planning framework is tested using a clinical non-small cell lung cancer (NSCLC) case. The results are compared with the conventional fractionation schedule (i.e., equal dose fractionation) as a reference plan. The results show that the proposed approach performed well in achieving a robust optimal ART treatment plan under high uncertainty in the biological parameters. The ART plan outperformed the reference plan by increasing the mean biological effective dose (BED) value of the tumor by 2.01%, while maintaining the OAR BED within +0.5% and reducing the variability, in terms of the interquartile range (IQR) of tumor BED, by 25%.

Influence of Hypofractionated Versus Conventional Fractionated Postmastectomy Radiation Therapy in Breast Cancer Patients With Reconstruction

We aimed to compare breast-related complications between hypofractionated adjuvant postmastectomy radiation therapy (PMRT) and conventional fractionated radiation therapy (RT) in patients with breast cancer undergoing reconstruction by reconstruction surgery type. Data from a total of 396 patients with breast cancer who underwent breast reconstruction after mastectomy between 2009 and 2018 were retrospectively reviewed. All patients received adjuvant PMRT according to either a conventional fractionation or hypofractionation schedule. We analyzed breast-related complications according to the timing of breast reconstruction (immediate or delayed). In cases of delayed reconstruction, only PMRT delivered before final delayed reconstruction was included. A major breast complication was defined as a breast-related toxicity that required reoperation or rehospitalization after the end of RT. The median follow-up time was 35.3 months (range, 8.8-122.7 months). Of all patients, 267 received immediate breast reconstruction and 129 received delayed breast reconstruction. In patients with immediate breast reconstruction, 91 were treated with conventional RT and 176 received hypofractionated RT. The occurrence of major breast-related complications did not differ significantly between the 2 fractionation regimens. Hypofractionated RT did not increase major wound problems (infection and dehiscence) compared with conventional RT. Furthermore, major contracture occurred significantly less frequently in hypofractionated RT. Of the patients who had delayed breast reconstruction, 48 received conventional RT and 81 received hypofractionated RT. There was no difference in the incidence of major breast complications between these 2 RT groups, and no difference in major breast complications were reported for either 1- or 2-stage delayed reconstruction. A time interval of >10 months between PMRT and final definitive reconstruction had a significantly lower incidence of major breast complications. Hypofractionated RT appears to be comparable with conventional fractionated RT in terms of breast-related complications in patients with breast cancer undergoing reconstruction, regardless of breast reconstruction type. An ongoing prospective randomized trial should confirm our findings.

Tumor control probability in hypofractionated radiotherapy as a function of total and hypoxic tumor volumes

Clinical studies in the hypofractionated stereotactic body radiotherapy (SBRT) have shown a reduction in the probability of local tumor control with increasing initial tumor volume. In our earlier work, we obtained and tested an analytical dependence of the tumor control probability (TCP) on the total and hypoxic tumor volumes using conventional radiotherapy model with the linear-quadratic (LQ) cell survival. In this work, this approach is further refined and tested against clinical observations for hypofractionated radiotherapy treatment schedules. Compared to radiotherapy with conventional fractionation schedules, simulations of hypofractionated radiotherapy may require different models for cell survival and the oxygen enhancement ratio (OER). Our TCP simulations in hypofractionated radiotherapy are based on the LQ model and the universal survival curve (USC) developed for the high doses used in SBRT. The predicted trends in local control as a function of the initial tumor volume were evaluated in SBRT for non-small cell lung cancer (NSCLC). Our results show that both LQ and USC based models cannot describe the TCP reduction for larger tumor volumes observed in the clinical studies if the tumor is considered completely oxygenated. The TCP calculations are in agreement with the clinical data if the subpopulation of radio-resistant hypoxic cells is considered with the volume that increases as initial tumor volume increases. There are two conclusions which follow from our simulations. First, the extent of hypoxia is likely a primary reason of the TCP reduction with increasing the initial tumor volume in SBRT for NSCLC. Second, the LQ model can be an acceptable approximation for the TCP calculations in hypofractionated radiotherapy if the tumor response is defined primarily by the hypoxic fraction. The larger value of OER in the hypofractionated radiotherapy compared to the conventional radiotherapy effectively extends the applicability of the LQ model to larger doses.

Dosimetric Comparison of Radiation Techniques for Comprehensive Regional Nodal Radiation Therapy for Left-Sided Breast Cancer: A Treatment Planning Study.

PurposeHow modern cardiac sparing techniques and beam delivery systems using advanced x-ray and proton beam therapy (PBT) can reduce incidental radiation exposure doses to cardiac and pulmonary organs individually or in any combination is poorly investigated.MethodsAmong 15 patients with left-sided breast cancer, partial wide tangential 3D-conformal radiotherapy (3DCRT) delivered in conventional fractionation (CF) or hypofractionated (HF) schedules; PBT delivered in a CF schedule; and volumetric modulated arc therapy (VMAT) delivered in an HF schedule, each under continuous positive airway pressure (CPAP) and free-breathing (FB) conditions, were examined. Target volume coverage and doses to organs-at-risk (OARs) were calculated for each technique. Outcomes were compared with one-way analysis of variance and the Bonferroni test, with p-values <0.05 considered significant.ResultsTarget volume coverage was within acceptable levels in all interventions, except for the internal mammary lymph node D95 (99% in PBT, 90% in VMAT-CPAP, 84% in VMAT-FB, and 74% in 3DCRT). The mean heart dose (MHD) was the lowest in PBT (<1 Gy) and VMAT-CPAP (2.2 Gy) and the highest in 3DCRT with CF/FB (7.8 Gy), respectively. The mean lung dose (MLD) was the highest in 3DCRT-CF-FB (20 Gy) and the lowest in both VMAT-HF-CPAP and PBT (approximately 5–6 Gy). VMAT-HF-CPAP and PBT delivered a comparable maximum dose to the left ascending artery (7.2 and 6.13 Gy, respectively).ConclusionsBoth proton and VMAT in combination with CPAP can minimize the radiation exposure to heart and lung with optimal target coverage in regional RT for left-sided breast cancer. The clinical relevance of these differences is yet to be elucidated. Continued efforts are needed to minimize radiation exposures during RT treatment to maximize its therapeutic index.

Tolerance and outcome of hypofractionated post-mastectomy radiotherapy among elderly breast cancer patients in a specialized center in Nigeria.

BackgroundThe incidence of breast cancer rises dramatically with age, and numerous studies have reported the benefits of post mastectomy radiotherapy in both young and elderly breast cancer patients. The limited numbers of radiotherapy machines and the conventional fractionation schedule which are of long duration make access to radiotherapy more difficult especially among the elderly in Nigeria. Hypo fractionated radiotherapy offers an alternative option (with a shorter duration and comparable side effects and outcomes) to conventional radiotherapy as reported in western literatures. Such studies are grossly lacking in a sub-Saharan African country like Nigeria, hence the need for this study.MethodsIn this retrospective study, the records of 83 elderly patients with stages II and III breast cancer that were treated with radiotherapy in the Radiotherapy and Oncology Department of UDUTH, Sokoto, Nigeria, from January 2015 to February 2019 were evaluated. Radiotherapy was given at a dose of 45 Gy in 18 fractions of 2.5 Gy to the chest wall and the regional lymph nodes over a period of 3.5 weeks. The end point was freedom from any grade 3 or higher toxicities and disease free survival at 2 years.ResultsMajority, 67 (80.7%) of the 83 patients had invasive ductal carcinoma which were not otherwise specific. About two-thirds of the patients (69.9%) had the disease located in the right breast. After a 24 month follow up, there were no grade 3 or 4 toxicities. Forty-two (50.6%) and 16 (19.2%) patients had grade 2 skin and nausea/vomiting toxicities respectively. Eighty (96.4%) were disease free at 24 months, 3 (3.6%) patients had local recurrence, while 1 (1.2%) had distant metastasis to the lungs. The two years overall survival rate was 90%.ConclusionsHypofractionated radiotherapy in elderly breast cancer patients proved to be comparable to conventional radiotherapy in terms of toxicities and outcome in our center.

Radiobiologically derived biphasic fractionation schemes to overcome the effects of tumour hypoxia

As a fractionated course of radiotherapy proceeds tumour shrinkage leads to resolution of hypoxia and the initiation of accelerated proliferation of radioresistant cancer cells with better repair capacity. We hypothesise that, in tumours with significant hypoxia, improved tumour control could be achieved with biphasic fractionation schedules that either use acceleration after 3-4 weeks of conventional radiotherapy or deliver a higher proportional dose towards the end of a course of treatment. We conducted a modelling study based on the concept of biological effective dose (BED) comparing such novel regimens with conventional fractionation. The comparator conventional fractionation schedule 70 Gy in 35 fractions delivered over 7 weeks was tested against the following novel regimens, both of which were designed to be isoeffective in terms of late normal tissue toxicity.40 Gy in 20 fractions over 4 weeks followed by 22.32 Gy in 6 consecutive daily fractions (delayed acceleration)30.4 Gy in 27 fractions over 4 weeks followed by 40 Gy in 15 fractions over 3 weeks (temporal dose redistribution)The delayed acceleration regimen is exactly identical to that of the comparator schedule over the first 28 days and the BED gains with the novel schedule are achieved during the second phase of treatment when reoxygenation is complete. For the temporal redistribution regimen, it was assumed that the reoxygenation fraction progressively increases during the first 4 weeks of treatment and an iterative approach was used to calculate the final tumour BED for varying hypoxic fractions. Novel fractionation with delayed acceleration or temporal fractionation results in tumour BED gains equivalent to 3.5-8 Gy when delivered in 2 Gy fractions. In hypoxic tumours, novel fractionation strategies result in significantly higher tumour BED in comparison to conventional fractionation. We demonstrate that novel biphasic fractionation regimens could overcome the effects of tumour hypoxia resulting in biological dose escalation.

A comparative study of two schedules of concomitant Chemo-radiation with Cisplatin in locally advanced Head and Neck Cancer in Southern Rajasthan of India

Introduction: Head and neck cancer is the most common cancer in south-central Asia. It constitutes about 17.7% of all cancers occurring in India. Majority of them present with locoregionally advanced stage. Concurrent chemo-radiotherapy (CCRT) is recognized worldwide as a standard treatment option for locally advanced disease not amenable to surgical resection. Aims: To compare the differences in acute toxicities and response rate between two schedules (weekly and 3-weekly divided dose cisplatin-based) of concomitant chemo-radiation (CCRT) regimens in locally advanced head and neck squamous cell carcinoma (LHNSCC). Methods and Material: Total of 62 eligible patients of LHNSCC who satisfying the eligibility criteria were included in this study. After pre-treatment evaluation, patients were sequentially randomized into two arms: 31 patients were taken in each arm, Arm-A (weekly concurrent cisplatin group) and Arm- B (three weekly divided dose concurrent cisplatin groups). One patient in each arm dropped out due to poor compliance. In both the arms, radiotherapy was delivered to a dose of 66-70 Gy with a telecobalt machine as a conventional fractionation schedule. The primary endpoints of the study were to know the disease response and assessment of acute toxicity profile in both arms. Results: Among the in-field toxicity, we found mucositis as the commonest toxicity in both arms. Incidence of Grade-III (33.33% vs 40%) & Grade-IV mucositis (6.66% vs 10%), acute gastrointestinal toxicity (Nausea- 33.33% vs 46.33% & vomiting- 13.33% vs 20%), and acute renal toxicity (16.66% vs 10%) were found to be slightly higher in 3-weekly arm compared to weekly arm. Our study showed that higher the incidence of neutropenia grade-I (23.33% VS 16.66%) and acute skin reaction (40% vs 33.33%) occurred in the weekly CCRT arm compared to the 3-weekly CCRT arm. In view of treatment compliance and response rate, our study showed 3-weekly arm have a higher compliance rate of scheduled chemotherapy cycles and a higher response rate (CR=80% vs 70%) compared to the weekly arm. Conclusions: The present study concluded that the three weekly divided dose concurrent cisplatin arms having a slightly better response rate with a slight increase in mucosal toxicity while the weekly concurrent cisplatin arm having a reduced requirement of feeding tube placement, colony-stimulating factor and hospitalization for supportive care.

Optimising efficacy and reducing toxicity of anticancer radioimmunotherapy.

Immunotherapy is radically changing the clinical management of patients affected by an increasingly wide array of tumours. However, not all patients achieve long-term clinical benefits from immunotherapy as a standalone treatment, calling for the development of regimens that combine various interventions. Radiotherapy stands out as a particularly promising candidate in this setting, not only because of its established safety profile, but also because radiotherapy has the potential ability to mediate robust immunostimulatory effects that could synergise with immunotherapy in systemic tumour control. However, optimal radioimmunotherapy regimens might call for the redefinition of conventional radiotherapy doses and fractionation schedules. In this Series paper, we discuss current approaches to improve the efficacy and reduce the toxicity of radioimmunotherapy for the management of cancer.

Prospective comparative study of pemetrexed and carboplatin versus paclitaxel and carboplatin as first-line chemotherapy in adenocarcinoma lung

Background: The worldwide epidemiology of lung cancer is ever changing, and non-squamous non-small-cell lung cancer (NSCLC) in never-smoking women has been gradually increasing. In Indian population, adenocarcinoma lung was more common in never smoker persons. Approximately 70–80% of lung cancer cases are NSCLC. Most of NSCLC patients present with advanced disease or brain metastasis. The prognosis of patients with advanced NSCLC is generally considered poor, with a median survival of 9–11 months and a 2-year survival around 20–30%. There are no enough data in Eastern India regarding disease response, treatment-related toxicity, overall survival, and progression-free survival in advanced adenocarcinoma lung treated with chemotherapy and radiotherapy. Objectives: The objectives of this study were to compare disease response, toxicity, overall survival, and progression-free survival in advanced adenocarcinoma lung treated as first line with pemetrexed/carboplatin versus paclitaxel/carboplatin. Materials and Methods: A total of 123 patients were placed in Group A and another 117 in Group B (stage III disease). Group A patients were treated with pemetrexed 500 mg/m2 and carboplatin area under the concentration (AUC) 6 every 3 week. Group B patients were treated with carboplatin at dose AUC 6 and paclitaxel 200 mg/m2 administered 3 weekly. Dose of radiation was planned 60 Gy in 30# for 6 weeks in conventional fractionation schedule 3 weeks after completion of chemotherapy. Results: Hematological toxicities were Grade 3 anemia 27 (22%) in Group A and 29 (24.8%) Group B, Grade 3 neutropenia 34 (27.6%) in Group A and 33 (28.2%) in Group B, and Grade 4 neutropenia 5 (4%) in Group A and 4 (3.4%) in Group B. Grade 3 sensory neuropathy was seen in Group B 17 (14.5%). There was no Grade 3 or Grade 4 sensory neuropathy in Group A. Grade 3 fatigue was seen in Group B 19 (16.2%). Grade 3 diarrhea was seen 9 (7.3%) in Group A and 8 (6.8%) in Group B. Overall response rate was 63 (51.2%) in Group A and 43 (36.8%) in Group B. The complete response of disease was 19 (15.4%) in Group A and 6 (5.1%) in Group B. The partial response was 44 (34.6%) in Group A and 37 (31.6%) in Group B. Stable disease was 41 (33.3%) in Group A and 51 (43.6%) in Group B. The progressive disease was 19 (15.4%) in Group A and 23 (19.6%) in Group B. Median overall survival was 14.6 months in Group A and 14.4 months in Group B. Conclusion: In our study, pemetrexed/carboplatin provides better efficacy and tolerance, a reduced need for supportive therapies, and more convenient administration than paclitaxel/carboplatin for the first-line treatment of patients with advanced adenocarcinoma lung.

Clinical T staging is superior to fluorodeoxyglucose positron emission tomography for predicting local outcomes after intra-arterial infusion chemoradiotherapy for maxillary sinus squamous cell carcinoma.

ABSTRACTConcomitant intra-arterial infusion chemoradiotherapy (IA-CRT) has been used to treat locally advanced maxillary sinus squamous cell carcinoma (MSSCC) with positive outcomes. However, an optimal predictive prognostic factor for MSSCC treated with IA-CRT remains elusive. The aim of the present study was to assess the feasibility of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), including volumetric parameters, to predict the prognosis of MSSCC treated with IA-CRT. Twenty-four patients with newly diagnosed MSSCC receiving FDG-PET imaging before IA-CRT treatment were analyzed in this retrospective study. All patients underwent radiotherapy with a total tumor dose of 60–66 Gy in a conventional fractionation schedule, using three-dimensional conformal radiation therapy or intensity-modulated radiation therapy. Radiotherapy was performed concurrently with concurrent intra-arterial infusion chemotherapy (cisplatin). The IA-CRT response rate was 83.33%. The 1- and 3-year survival rates were 81.30% and 64.34%, respectively. The 1- and 3-year local failure-free rates were 57.21% and 40.96%, respectively. Local failure was significantly associated with poor survival (P = 0.0152). Further, clinical T staging clearly stratified local control outcomes among patients with clinical T3 or less, T4a, and T4b (P = 0.0312). Moreover, patients with stage T4b showed a significantly poorer local control compared with T3 or less (P = 0.0103). However, FDG-PET parameters provided no significant predictive information regarding treatment outcome. To conclude, pretreatment T stage predicts local control by IA-CRT, which is associated with survival.

Radiotherapy of pancreatic cancer in older patients: A systematic review.

Pancreatic cancer (PaC) will soon be one of the main causes of cancer mortality. Furthermore, its incidence is higher in the older population and radiotherapy (RT) represents a treatment option. The aim of this review was to evaluate feasibility and outcome of RT in older patients with PaC. A systematic literature review of patients aged ≥65 years with PaC treated with RT was performed using the PRISMA methodology. Eleven papers (1830 patients) fulfilled our inclusion criteria and were analyzed. RT was prescribed either alone or as an adjuvant treatment. Prescribed RT dose ranged from 22.0 to 70.0 Gy with conventional fractionation or hypo-fractionated schedule and delivered by three-dimensional conformal RT, intensity modulated RT or stereotactic body RT. Grade ≥ 3 acute and grade ≥ 2 late toxicity rates ranged between 0.0% and 52.6% (median: 0.5%) and between 0.0% and 15.0% (median: 0%), respectively. Median overall survival and two-year survival rate were 11.3 months (range: 6.4-69.0 months) and 49.0% (range 6.6-75.5%), respectively. RT in older patients seems to be tolerable and safe particularly in terms of late toxicity irrespective of the treatment settings. Therefore, RT can represent a treatment option in PaC even in an older population. Further analyses and prospective trials enrolling older patients are needed to better define the risk/benefit ratio in different treatment settings.

Current and emerging radiotherapy strategies for pancreatic adenocarcinoma: stereotactic, intensity modulated and particle radiotherapy

The role of radiotherapy for locally advanced pancreatic cancer (LAPC) is unclear based on studies that used conventional doses and fractionation schedules. Modern radiotherapy techniques have not been studied in depth, however. We reviewed the literature on emerging methods of delivering higher doses of conformal radiotherapy using stereotactic body radiation, intensity modulated radiation, and particle beam radiation, highlighting clinical outcomes and toxicities. The literature review suggests low rates of acute and late toxicities when higher doses of radiation are given with careful attention to normal tissue dose constraints, including for stereotactic body radiotherapy (SBRT), escalated doses with intensity modulated radiation therapy (IMRT), and particle-based therapy. Retrospective evidence suggests prolonged survival for patients who receive biological equivalent doses above 70 Gy. Prospective trials that evaluate modern radiotherapy techniques are warranted for LAPC.