Summary Use of proton beam therapy has expanded, with the number of proton centres rapidly increasing not only in the USA but also worldwide. The physical characteristics of the proton beam offer ...important advantages versus widely used photon techniques in terms of radiation precision. In head and neck cancer in particular, proton beam therapy is uniquely suited for the complex anatomy of tumours and sensitive surrounding organs. De-intensification and personalisation of treatment to limit toxicity are of renewed importance in the context of human papilloma virus-associated disease, in which young patients will be cured but bear the consequences of adverse effects for decades. Comparisons of radiation dose distributions between photon and proton techniques suggest considerable benefit in terms of toxicity sparing, but this has only recently been confirmed by substantial clinical data. In this Review, we attempt to define the role of this method in the contemporary multidisciplinary management of various types of head and neck cancer.
To report a small substudy of an ongoing large, multi-arm study using functional imaging to assess pre-/intratreatment hypoxia for all head and neck cancer, in which we hypothesized that pre- and ...early-treatment hypoxia assessment using functional positron emission tomography (PET) imaging may help select which human papillomavirus (HPV)-positive (HPV(+)) oropharyngeal cancer (OPC) patients can safely receive radiation de-escalation without jeopardizing treatment outcomes.
Patients with HPV(+) oropharyngeal carcinoma were enrolled on an institutional review board-approved prospective study of which de-escalation based on imaging response was done for node(s) only. Pretreatment (18)F-fluorodeoxyglucose and dynamic (18)F-FMISO (fluoromisonidazole) positron emission tomography (PET) scans were performed. For patients with pretreatment hypoxia on(18)F-FMISO PET (defined as a >1.2 tumor to muscle standard uptake value ratio), a repeat scan was done 1 week after chemoradiation. Patients without pretreatment hypoxia or with resolution of hypoxia on repeat scan received a 10-Gy dose reduction to metastatic lymph node(s). The 2-year local, regional, distant metastasis-free, and overall survival rates were estimated using the Kaplan-Meier product-limit method. A subset of patients had biopsy of a hypoxic node done under image guidance.
Thirty-three HPV(+) OPC patients were enrolled in this pilot study. One hundred percent showed pretreatment hypoxia (at primary site and/or nodes), and among these, 48% resolved (at primary site and/or nodes); 30% met criteria and received 10-Gy reduction to the lymph node(s). At the median follow-up of 32 months (range, 21-61 months), the 2-year locoregional control rate was 100%. One patient failed distantly with persistence of hypoxia on (18)F-FMISO PET. The 2-year distant metastasis-free rate was 97%. The 2-year OS rate was 100%. Hypoxia on imaging was confirmed pathologically.
Hypoxia is present in HPV(+) tumors but resolves within 1 week of treatment in 48% of cases either at the primary site and/or lymph node(s). Our 100% locoregional control rate suggests that intratreatment functional imaging used to selectively de-escalate node(s) to 60 Gy was confirmed safe using our stringent imaging criteria. Intratreatment functional imaging warrants further study to determine its ultimate role in de-escalation treatment strategies.
Abstract Purpose This study aimed to evaluate the toxicity of prostate and pelvic lymph node stereotactic body radiation therapy (SBRT) for high-risk prostate cancer. Methods and Materials ...Twenty-three patients with high-risk or lymph node-positive prostate cancer were treated with SBRT that delivered 37.5 to 40 Gy in 5 fractions to the prostate and seminal vesicles, with concomitant treatment of the pelvic nodes to 25 Gy. In general, patients received neoadjuvant, concurrent, and adjuvant androgen deprivation therapy for a duration of 18 months. Toxicities were evaluated with the Common Terminology Criteria for Adverse Events, version 3.0. The median follow-up was 19 months (range, 3-48 months). Results Acute grade 1 gastrointestinal (GI) toxicities were noted in 2 patients (9.1%). No patient experienced acute grade ≥2 GI toxicity. Acute genitourinary (GU) grade 1, 2, and 3 toxicities were observed in 7 patients (31.8%), 8 patients (36.4%), and 1 patient (4.5%), respectively. Late grade 2 GI and GU toxicities were observed in 2 patients (9.1%) and 6 patients (27.3%), respectively. No late grade ≥3 GI toxicity was noted. Late grade ≥3 GU (hemorrhagic cystitis) was noted in 1 patient (4.5%), which responded to laser fulguration. Conclusions SBRT with pelvic lymph node radiation therapy was feasible and well tolerated. The incidence of grade ≥3 GU and GI toxicities was uncommon. Continued follow-up will be required to determine the long-term safety and efficacy of this approach for high-risk patients.
AbstractPurposeTo report 15-year outcomes for dose-escalated intensity modulated radiation therapy (IMRT) for localized prostate cancer (PC) by evaluating biochemical relapse, distant metastases, ...cancer-specific survival, and long-term toxicity.Methods and materialsA database search was conducted for the first cohort of patients treated at this institution with 81 or 86.4 Gy between 1996 and 1998 using IMRT. Toxicity data were scored according to the Common Terminology Criteria for Adverse Events version 3.0. Median follow-up was 11.6 years (range, 5-21 years).ResultsIn the study, 301 patients were treated with 81 Gy (n = 269, 89%) or 86.4 Gy (n = 32, 11%). Patients were analyzed by National Comprehensive Cancer Network risk group, with 29% low risk (LR), 49% intermediate risk (IR), and 22% high risk (HR). Late grade 3 gastrointestinal (GI) toxicity was seen in 3 patients (1.0%). No grade 4 GI toxicity events occurred. Median time from radiation therapy to late grade 3 GI toxicity was 2.9 years. One event occurred after 10 years. Late grade 3 and 4 genitourinary (GU) toxicity was seen in 6 (2.0%) and 1 (0.3%) patient, respectively. Median time to late grade 3+ GU toxicity was 5.5 years. Two events occurred after 10 years. In addition, 38 (12.6%) developed second primary malignancies (SPMs), 8 of which were in-field malignancies. Median time from radiation therapy to all SPM and in-field SPM was 10 years. The 15-year relapse-free survival was 76%, 65%, and 55% in the LR, IR, and HR groups, respectively. Distant metastases-free survival was 88%, 75%, and 63% for LR, IR, and HR patients, respectively. PC-specific mortality was 1.9%, 7.1%, and 12.2% for LR, IR, and HR patients.ConclusionsThis report represents the longest follow-up data set to our knowledge of patients treated with high-dose IMRT for PC. Our findings indicate that it is well tolerated with 1.0% and 2.3% incidence of long-term grade 3+ GI and GU toxicity, respectively. The cohort had excellent PC-specific survival.
Abstract Objective To evaluate a multimodal strategy aimed at treating all sites of disease that provides a rapid readout of success or failure in men presenting with noncastrate metastatic prostate ...cancers that are incurable with single modality therapy. Patients and Methods Twenty selected men with oligometastatic M1a (extrapelvic nodal disease) or M1b (bone disease) at diagnosis were treated using a multimodal approach that included androgen deprivation, radical prostatectomy plus pelvic lymphadenectomy (retroperitoneal lymphadenectomy in the presence of clinically positive retroperitoneal nodes), and stereotactic body radiotherapy to osseous disease and/or the primary site. Outcomes of each treatment were assessed sequentially. Androgen deprivation was discontinued in responding patients. The primary endpoint was an undetectable prostate-specific antigen (PSA) after testosterone recovery. The goal was to eliminate all detectable disease. Results Each treatment modality contributed to the outcome: 95% of the cohort achieved an undetectable PSA with multimodal treatment, including 25% of patients after androgen deprivation alone and an additional 50% and 20% after surgery and radiotherapy, respectively. Overall, 20% of patients (95% confidence interval 3-38%) achieved the primary endpoint, which persisted for 5, 6, 27+, and 46+ months. All patients meeting the primary endpoint had been classified with M1b disease at presentation. Conclusion A sequentially applied multimodal treatment strategy can eliminate detectable disease in selected patients with metastatic spread at diagnosis. The endpoint of undetectable PSA after testosterone recovery should be considered when evaluating new approaches to rapidly set priorities for large-scale testing in early metastatic disease states and shifts the paradigm from palliation to cure.
The risk of cardiac injury with hypofractionated whole-breast/chest wall radiation therapy (HF-WBI) compared with conventional whole-breast/chest wall radiation therapy (CF-WBI) in women with ...left-sided breast cancer remains a concern. The purpose of this study was to determine if there is an increase in hospital-related morbidity from cardiac causes with HF-WBI relative to CF-WBI.
Between 1990 and 1998, 5334 women ≤ 80 years of age with early-stage breast cancer were treated with postoperative radiation therapy to the breast or chest wall alone. A population-based database recorded baseline patient, tumor, and treatment factors. Hospital administrative records identified baseline cardiac risk factors and other comorbidities. Factors between radiation therapy groups were balanced using a propensity-score model. The first event of a hospital admission for cardiac causes after radiation therapy was determined from hospitalization records. Ten- and 15-year cumulative hospital-related cardiac morbidity after radiation therapy was estimated for left- and right-sided cases using a competing risk approach.
The median follow-up was 13.2 years. For left-sided cases, 485 women were treated with CF-WBI, and 2221 women were treated with HF-WBI. Mastectomy was more common in the HF-WBI group, whereas boost was more common in the CF-WBI group. The CF-WBI group had a higher prevalence of diabetes. The 15-year cumulative hospital-related morbidity from cardiac causes (95% confidence interval) was not different between the 2 radiation therapy regimens after propensity-score adjustment: 21% (19-22) with HF-WBI and 21% (17-25) with CF-WBI (P=.93). For right-sided cases, the 15-year cumulative hospital-related morbidity from cardiac causes was also similar between the radiation therapy groups (P=.76).
There is no difference in morbidity leading to hospitalization from cardiac causes among women with left-sided early-stage breast cancer treated with HF-WBI or CF-WBI at 15-year follow-up.
To report the early outcomes for very young children with medulloblastoma or supratentorial primitive neuroectodermal tumor (SPNET) treated with upfront chemotherapy followed by 3-dimensional proton ...radiation therapy (3D-CPT).
All patients aged <60 months with medulloblastoma or SPNET treated with chemotherapy before 3D-CPT from 2002 to 2010 at our institution were included. All patients underwent maximal surgical resection, chemotherapy, and adjuvant 3D-CPT with either craniospinal irradiation followed by involved-field radiation therapy or involved-field radiation therapy alone.
Fifteen patients (median age at diagnosis, 35 months) were treated with high-dose chemotherapy and 3D-CPT. Twelve of 15 patients had medulloblastoma; 3 of 15 patients had SPNET. Median time from surgery to initiation of radiation was 219 days. Median craniospinal irradiation dose was 21.6 Gy (relative biologic effectiveness); median boost dose was 54.0 Gy (relative biologic effectiveness). At a median of 39 months from completion of radiation, 1 of 15 was deceased after a local failure, 1 of 15 had died from a non-disease-related cause, and the remaining 13 of 15 patients were alive without evidence of disease recurrence. Ototoxicity and endocrinopathies were the most common long-term toxicities, with 2 of 15 children requiring hearing aids and 3 of 15 requiring exogenous hormones.
Proton radiation after chemotherapy resulted in good disease outcomes for a small cohort of very young patients with medulloblastoma and SPNET. Longer follow-up and larger numbers of patients are needed to assess long-term outcomes and late toxicity.
The abscopal effect is defined when a form of local therapy causes tumor regression of both the target lesion and any untreated tumors. Herein cases of the abscopal effect were systematically ...reviewed and a patient-level data analysis was performed for clinical predictors of both duration of response and survival.
The Population, Intervention, Control, Outcome, Study (PICOS) design approach, Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) literature selection process, and Meta-analysis of Observational Studies in Epidemiology (MOOSE) were used to find articles published before September 2019 in MEDLINE/PubMed and Google Scholar. Inclusion criteria were (1) population: patients with reported abscopal response; (2) intervention: documented treatment(s); (3) control: none; (4) outcomes: overall and progression-free survival; and (5) setting: retrospective case reports. Time from treatment until abscopal response and time from abscopal response until progression/death were calculated. Univariate and multivariate analyses were conducted for survival outcomes.
Fifty studies (n = 55 patients) were included. Median age was 65 years (interquartile range IQR, 58-70) and 62% were male. Fifty-four (98%) patients received radiation therapy, 34 (62%) received radiation therapy alone, 5 (9.1%) underwent surgery, 4 (7.3%) received chemotherapy, and 11 (20%) received immunotherapy. Median total dose was 32 Gy (IQR, 25.5-48 Gy) and median dose per fraction was 3 Gy (IQR, 2-7.2). Median time until abscopal response was 4 months (IQR, 1-5; min 0.5, max 24). At 5 years, overall survival was 63% and distant progression-free survival was 45%. No variables had statistical significance in predicting duration of response or survival.
Almost all reported cases of the abscopal response are after radiation therapy; however, there are no known predictors of duration of response or survival in this population.
Although hydrogel spacer placement (HSP) minimizes rectal dose during prostate cancer radiation therapy, its potential benefit for modulating rectal toxicity could depend on the achieved ...prostate-rectal separation. We therefore developed a quality metric associated with rectal dose reduction and late rectal toxicity among patients treated with prostate stereotactic body radiation therapy (SBRT).
A quality metric consisting of prostate-rectal interspace measurements from axial T2-weighted magnetic resonance imaging simulation images was applied to 42 men enrolled in a multi-institutional phase 2 study using HSP with prostate SBRT (45 Gy in 5 fractions). A score of 0, 1, or 2 was assigned to a prostate-rectal interspace measurement of <0.3 cm, 0.3 to 0.9 cm, or ≥1 cm, respectively. An overall spacer quality score (SQS) was computed from individual scores at rectal midline and ±1 cm laterally, located at the prostate base, midgland, and apex. Associations of SQS with rectal dosimetry and late toxicity were evaluated.
The majority of the analyzed cohort had an SQS of 1 (n = 17; 41%) or 2 (n = 18; 43%). SQS was associated with maximum rectal point dose (rectal Dmax; P = .002), maximum dose to 1 cc of rectum (D1cc; P = .004), and volume of rectum receiving ≥100% of prescription dose (V45; P = .046) and ≥40 Gy (V40; P = .005). SQS was also associated with a higher incidence of (P = .01) and highest-graded late rectal toxicity (P = .01). Among the 20 men who developed late grade ≥1 rectal toxicity, 57%, 71%, and 22% had an SQS of 0, 1, and 2, respectively. Men with an SQS of 0 or 1 compared with 2 had 4.67-fold (95% CI, 0.72-30.11) or 8.40-fold (95% CI, 1.83-38.57) greater odds, respectively, of developing late rectal toxicity.
We developed a reliable and informative metric for assessing HSP, which appears to be associated with rectal dosimetry and late rectal toxicity after prostate SBRT.
Radiation treatment plans undergo peer review during chart rounds, but changes to treatment volumes would require replanning. Our group implemented weekly head and neck cancer “volume rounds” to peer ...review all target volumes for head and neck cancer before radiation therapy (RT) planning and chart rounds.
We analyzed modifications made to planning target volumes (PTVs) at volume rounds for consecutive nonproton head and neck cancer cases from May 2020 to May 2021. Nine head and neck radiation oncologists participated in weekly volume rounds during this time. Recommendations were categorized as no changes, minor changes, major changes, additional workup (eg, biopsy or imaging), and consultation or tumor board discussion needed before the start of RT. Minor changes to PTVs generally did not require a second review before treatment planning while major changes did.
PTVs for 511 cases involving 432 patients underwent peer review and 298 (58.3%) of these cases did not require any modifications before treatment planning. Minor and major changes were recommended in 75 (14.7%) and 86 (16.8%) cases, respectively. Forty-five (8.8%) cases were recommended to have additional workup and 23 (4.5%) required additional consultation with nonradiation surgeons or medical oncologists. Of the 45 cases that were recommended for additional workup, 40 underwent biopsy or imaging. Positive findings on imaging or biopsy occurred in 13 patients, leading to a significant change in management, including 4 patients who underwent additional surgery after positive findings before the start of RT.
Prospective peer review during head and neck cancer volume rounds led to frequent minor and major alterations to PTVs. Significant changes in the overall treatment plan, such as additional surgery before start of RT, occurred in a minority of patients.
PDF
