Hypofractionated Pencil-Beam Scanning Intensity-modulated Proton Therapy (IMPT) in Recurrent Rectal Cancer

* MTD is defined as the dose associated with a 35% probability of dose-limiting toxicity (DLT). * DLT is defined as any toxicity listed below that occurs within 6 months from start of treatment and is considered possibly, probably, or definitely related to proton reirradiation: * Any grade 5 toxicities * Any grade 4-5 GI toxicities * Bowel obstruction * Grade 3-5: diarrhea; anal, colonic, or bowel ulcers; bladder perforation; any fistula formations; peripheral motor/sensory neuropathy of the pelvis above baseline; osteonecrosis/soft tissue necrosis; radiation dermatitis; hematuria; hematochezia; bowel/pelvic hemorrhage; reproductive tract toxicity * Toxicity will be graded using CTCAE v5

Time frame: From start of treatment through 6 months

Population: 3 participants are not evaluable for this outcome measure. 2 participants did not start treatment. 1 participant was erroneously treated with dose level -1 (25 Gy) which is not part of the dose levels defined in the protocol.

-DRE, endoscopy, and cross-sectional imaging will be used to measure clinical complete response rate

Time frame: Within 6 weeks to 3 months post-completion of radiation therapy (range 7-14 weeks)

Population: 1 participant is not evaluable in Dose Level 1 because they did not start treatment. 1 participant is not evaluable in Dose Level 3 because they did not start treatment. 1 participant was erroneously treated with dose level -1 (25 Gy) which is not part of the dose levels defined in the protocol and was excluded from this outcome measure as data was not collected on the patient.

Time frame: From start of treatment through 3 months after completion of radiation therapy (estimated to be 3 months and 1 week)

Population: 1 participant is not evaluable in Dose Level 1 because they did not start treatment. 1 participant is not evaluable in Dose Level 3 because they did not start treatment.

Time frame: From 3 month post-completion of radiation therapy to 12 months post-completion of radiation therapy

Population: 1 participant is not evaluable in Dose Level 1 because they did not start treatment. 1 participant is not evaluable in Dose Level 3 because they did not start treatment. 1 participants in Dose Level -1 is not evaluable as patient did not have follow-up to evaluate for late adverse effects.

29 question survey which assesses quality of life for patients with colorectal cancer including functional & symptom status. The survey includes 4 multi-item scales & 19 single-item scales. Scores are linearly transformed to provide a score from 0-100. A high score for functional scales represents high level of functioning, while a high score for symptom scale represents high level of symptoms. Median scores were taken for each scale & the difference between baseline & varying time points was reported. Negative value represents improved function for a functional scale item, & worsening symptoms for symptom scale items. Positive values represent the converse. If patients did not complete the survey at each time point, their data was censored. Data values were averaged from 3-12 months. Differences were taken between baseline values and the average value calculated of post-RT from 3-12 months

Time frame: Assessed at pre-treatment (baseline), 1-2 weeks, 3 months, 6 months, 9 months, and 12 months post-treatment

Population: This outcome measure includes data for participants who completed the questionnaire. If a participant did not complete the questionnaire at a specific time point, then the participant is not included in the number analyzed at that time point. 1 participant was erroneously treated with dose level -1 (25 Gy) which is not part of the dose levels defined in the protocol and was excluded from this outcome measure as data was not collected on the participant.

29 question survey which assesses quality of life for patients with colorectal cancer including functional & symptom status. The survey includes 4 multi-item scales & 19 single-item scales. Scores are linearly transformed to provide a score from 0-100. A high score for functional scales represents high level of functioning, while a high score for symptom scale represents high level of symptoms. Median scores were taken for each scale & the difference between baseline & varying time points was reported. Negative value represents improved function for a functional scale item, & worsening symptoms for symptom scale items. Positive values represent the converse. If patients did not complete the survey at each time point, their data was censored. Data values were averaged prior to 3 months. Differences were taken between pre-treatment (baseline) values and the average value calculated of post-RT up to 3 months.

Time frame: Assessed at pre-treatment (baseline), 1-2 weeks, 3 months, 6 months, 9 months, and 12 months post-treatment

Population: This outcome measure includes data for participants who completed the questionnaire. If a participant did not complete the questionnaire at a specific time point, then the participant is not included in the number analyzed at that time point. 1 participant was erroneously treated with dose level -1 (25 Gy) which is not part of the dose levels defined in the protocol and was excluded from this outcome measure as data was not collected on the participant.

30 question survey which assesses patient well-being with 5 functional scales, 9 symptom scales, & global health scale. Scores for each scale range from 0-100. Higher score for the functional scale & global health represent high functioning, while high score for symptom scale represents high symptomatology. Median scores were taken for each scale for each dose level and the different between pre-treatment and post-treatment scores were calculated to determine change in score over time. For functional scales and global health status, negative values represent improved functionality/quality of life, while positive values represent diminished functionality. For symptom scales, the opposite is true. If patients did not complete the survey at each time point, their data was censored. Data values were averaged from 3-12 months. Differences were taken between baseline values and the average value calculated of post-RT from 3-12 months.

Time frame: Assessed at pre-treatment (baseline), 1-2 weeks, 3 months, 6 months, 9 months, and 12 months post-treatment

Population: This outcome measure includes data for participants who completed the questionnaire. If a participant did not complete the questionnaire at a specific time point, then the participant is not included in the number analyzed at that time point. 1 participant was erroneously treated with dose level -1 (25 Gy) which is not part of the dose levels defined in the protocol and was excluded from this outcome measure as data was not collected on the participant.

30 question survey which assesses patient well-being with 5 functional scales, 9 symptom scales, & global health scale. Scores for each scale range from 0-100. Higher score for the functional scale & global health represent high functioning, while high score for symptom scale represents high symptomatology. Median scores were taken for each scale for each dose level and the different between pre-treatment and post-treatment scores were calculated to determine change in score over time. For functional scales and global health status, negative values represent improved functionality/quality of life, while positive values represent diminished functionality. For symptom scales, the opposite is true. If patients did not complete the the survey at each time point, their data was censored. Data values were averaged prior to 3 months. Differences were taken between baseline values and the average value calculated of post-RT up to 3 months.

Time frame: Assessed at pre-treatment (baseline), 1-2 weeks, 3 months, 6 months, 9 months, and 12 months post-treatment

Population: This outcome measure includes data for participants who completed the questionnaire. If a participant did not complete the questionnaire at a specific time point, then the participant is not included in the number analyzed at that time point. 1 participant was erroneously treated with dose level -1 (25 Gy) which is not part of the dose levels defined in the protocol and was excluded from this outcome measure as data was not collected on the participant.

-Defined as time from end of radiation therapy to date of first instance of local or regional tumor progression

Time frame: Through completion of follow-up (full range 1.81 months-13.87 months)

Population: 1 participant is not evaluable in Dose Level 1 because they did not start treatment. 1 participant is not evaluable in Dose Level 3 because they did not start treatment. 1 participant was erroneously treated with dose level -1 (25 Gy) which is not part of the dose levels defined in the protocol and was excluded from this outcome measure as data was not collected on the patient.

Defined as time from end of radiation therapy to date that at least 50% of patients died

Time frame: Through completion of follow-up (full range 4.4 months to 13.87 months)

Population: 1 participant is not evaluable in Dose Level 1 because they did not start treatment. 1 participant is not evaluable in Dose Level 3 because they did not start treatment. 1 participant was erroneously treated with dose level -1 (25 Gy) which is not part of the dose levels defined in the protocol and was excluded from this outcome measure as data was not collected on the patient.

-Defined as time from end of radiation therapy to the earliest date of locoregional progression, distant progression, or death from any cause

Time frame: Through completion of follow-up (full range 1.81 months-13.87 months)

Population: 1 participant is not evaluable in Dose Level 1 because they did not start treatment. 1 participant is not evaluable in Dose Level 3 because they did not start treatment. 1 participant was erroneously treated with dose level -1 (25 Gy) which is not part of the dose levels defined in the protocol and was excluded from this outcome measure as data was not collected on the patient.